Nature: Biological Features Of H7N9

Credit CDC

 

 

# 7444

 

 

A study, published today in the Journal Nature, provides new insights into the H7N9 avian flu virus which emerged on the Chinese mainland earlier this spring, and suggests that should it return this winter, it could prove a far more formidable foe than than has H5N1 to date.

 

Chinese researchers, looking both at the virus in the laboratory, and at patient responses to infection, have concluded that this virus `poses a potentially high risk to humans.’.

 

Among their findings:

 

• Unlike the H5N1 virus – which binds preferentially to avian receptor cells (a2,3-linked sialic acid) -  H7N9 binds to both the avian and human (a2,6-linked sialic acid) receptor cells.

• This dual receptor cell binding ability likely enhances the virus’s ability to transmit from birds to humans.

• The virus appears to replicate well in the lower human respiratory tract - but less well in the trachea – which may have helped to limit its ability to spread from human-to-human.

• Once infected, the virus often produces severe illness in humans, and patients tested showed increased serum levels of chemokines and cytokines, suggesting the possibility of infection inducing a `cytokine storm’.

• There appears to be little  or no community immunity to H7 viruses.

 

 

First, a link to the letter in Nature (the abstract is available, but the whole letter is behind a pay wall). Given the barebones nature of the abstract, I’ll return with a little more background on some of their findings.

 

Biological features of novel avian influenza A (H7N9) virus

Jiangfang Zhou1*,DayanWang1*,RongbaoGao1*, Baihui Zhao2*, Jingdong Song1,XianQi3 ,Yanjun Zhang4, Yonglin Shi 5, LeiYang1, Wenfei Zhu1, Tian Bai 1,KunQin1, Yu Lan1, Shumei Zou1, JunfengGuo1, JieDong1 , LiboDong1 ,Ye Zhang1, HejiangWei 1, Xiaodan Li 1, Jian Lu1 , Liqi Liu1 , Xiang Zhao1, Xiyan Li 1, Weijuan Huang1, LeyingWen1 ,HongBo1 , Li Xin1, Yongkun Chen1 , Cuilin Xu1, Yuquan Pei 6,YueYang6 , Xiaodong Zhang6, ShiwenWang1,  Zijian Feng7 , JunHan7 ,Weizhong Yang7, George F. Gao7 , GuizhenWu1 ,Dexin Li 1, Yu Wang7 & Yuelong Shu1

 

 

Highlighting a few points raised by this study.

 

The authors note that H7N9:`. . .can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli . . ‘.

 

Pneumocytes (aka pneumonocytes) are a collective term for the two types of cells lining the alveoli (the air sacs) in the lung; Type I and Type II pneumocytes.

 

• Type I pneumocytes are responsible for the gas exchange (02 and C02) between the lungs and the blood stream.  Type I pneumocytes are easily damaged and cannot reproduce themselves.

• Type II pneumocytes are responsible for the production of surfactant, which reduces the surface tension of pulmonary fluids and contributes to the elasticity of the lungs.  

• Type II pneumocytes are able to replicate in the alveoli and can create new Type I pneumocytes.

 

A loss of type II pneumocytes can severely degrade the lungs ability to fight off an infection, and to repair damaged tissue. Earlier studies have demonstrated tropism for, and destruction of, type II pneumocytes by the avian H5N1 virus.

 

While still only partially understood, the idea behind a `cytokine storm’ is that the host’s immune system goes into overdrive, producing excessive levels of cytokines that can provoke damaging inflammation in the lungs.

 

Cytokines are a category of signaling molecules that are used extensively in cellular communication. They are often released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.

 

This cascade of immune cells rushing to the infection, if it races out of control, can literally kill the patient. Their lungs can fill with fluid (which makes a terrific medium for a bacterial co-infection), and cells in the lungs (Type 1 & Type II Pneumocytes) can sustain severe damage.

 

Previously, in Swine Flu Sequelae and Cytokine Storm Warnings, we looked at some of the severe lung damage during the 2009 pandemic that was thought to be due to this overreaction of the immune system.

 

You can find more on this theory in these earlier posts:

 

Study: Calming The Cytokine Storm

Cytokine Storm Warnings

The Baskin Influenza Pathogenesis Study

Pt. 1               Pt. 2             Pt. 3

 

Another finding (across all age groups tested) was a lack of pre-existing immunity to the H7N9 virus, and that the current seasonal vaccine conveyed absolutely no protection.

 

As we’ve discussed earlier, while work is underway on creating seed strains for an H7N9 vaccine, getting one through the testing and manufacturing process and into the arms of hundreds of millions of people, is unlikely to happen in the near term (see JAMA: Challenges Of Producing An Effective & Timely H7N9 Vaccine).

 

For now, the saving grace with this virus is its apparent inability to spread efficiently from human-to-human. But should that change, the world could find itself facing a particularly nasty pandemic threat.

CIDRAP: Children & Middle-Aged Most Susceptible To H3N2v

Credit Wikipedia

 

# 6489

 

Robert Roos of CIDRAP has an excellent report on a study – published on Aug 7th in The Journal of Infectious Diseases – that looks at pre-existing, and vaccine-induced immunity to the emerging H3N2v swine flu virus by age cohorts.

 

This serological study, conducted in Canada, is called :

 

Cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v

Danuta M. Skowronski, Naveed Z. Janjua, Gaston De Serres3, Dale Purych, Vladimir Gilca, David W. Scheifele, Marc Dionne, Suzana Sabaiduc, Jennifer L. Gardy, Guiyun Li, Nathalie Bastien, Martin Petric, Guy Boivin and Yan Li

 

 

Below is Robert’s report on these findings, and as I’m hardly likely to improve upon his work, I’ll simply invite you to follow the link below and read:

 

Study: Children, middle-aged most vulnerable to variant H3N2

Robert Roos News Editor

Aug 10, 2012 (CIDRAP News) – A serologic study from Canada suggests that children and middle-aged adults have little or no immunity to the swine-origin variant H3N2 influenza virus (H3N2v), but about half of adolescents and young adults have some degree of immunity as measured by antibody levels.

(Continue . . .)

 

Robert’s story mentioned earlier studies with similar findings, and you can find details on them in these earlier blogs:

 

Last April in MMWR: Antibodies Cross-Reactive to Influenza A (H3N2) Variant Virus, we saw a study that found that children under the age of ten were practically devoid of antibodies to this virus, and were likely the most susceptible to infection.

 

A few months before, in Eurosurveillance: Older People May Be Susceptible To The H3N2v Virus), we saw evidence that the moderate levels of immunity detected in adolescent and young adult populations declined with age.

 

In other H3N2v news, Lisa Schnirring of CIDRAP has a excellent roundup, including the release of new interim clinician guidelines, the poor reliability of RIDTs (Rapid Influenza Detection Tests) with this virus, and an age breakdown of confirmed cases that now includes 10 adults.

 

CDC updates novel H3N2 info for clinicians

Lisa Schnirring Staff Writer

Aug 10, 2012 (CIDRAP News) – The US Centers for Disease Control and Prevention (CDC) today reported that it has received 153 reports of novel H3N2 infections (H3N2v) since illnesses started surfacing in the middle of July, nearly all of them in people who had contact with pigs or were around pigs at fairs.

 

In another development, the CDC issued new information on H3N2v for clinicians, including an evaluation of rapid influenza tests that found their sensitivity varies greatly, and the agency urged clinicians not to use negative results as the basis for treatment.

(Continue . . . )

 

 

A blogger’s Note:

 

The slow emergence of this swine H3N2v virus into the human population is a fascinating story, and one that certainly deserves ongoing coverage.  But at the same time, the last thing this story needs is unwarranted hype.

 

According to the CDC, this virus has not adapted well enough to human physiology to spark a pandemic.  Nearly all confirmed cases appear to be the result of direct contact with an infected pig.

 

Sustained and efficient Human-to-Human transmission does not appear to be occurring at this time.

 

The caveat being, that over time, that could change.

 

For now, this virus is less a public health threat story and more an opportunity for us to learn how these types of viruses evolve in swine and (on rare occasion) seep into the human population.

 

A cautionary tale, if you will, on how nature’s laboratory is open 24/7 - constantly trying out new viral combinations - looking for an evolutionary advantage.

 

The dilemma, from my standpoint, is how to cover this story responsibly. 

 

Rather than rush to post a blog every time we get an updated case count, for my own sanity, I’ve decided only to blog on the H3N2v virus when there is something more substantial to report.

 

This weekend I’ll explore the possibility of keeping a daily update `State Confirmed H3N2v Cases’ in my sidebar, at least until that becomes too unwieldy.

 

Even so, I’m sure H3N2v will get ample attention in these pages.

 

As we wait to see what this H3N2v virus ends up doing - between seasonal flu, bird flu, swine flu, seal flu, and bat flu, plus non-flu related stories - I’m confident there will be no shortage of topics to blog about.

Study: Initial Flu Dose Dictates Immune Response

 

H3N2 influenza virions –CDC PHIL

 

# 6408

 

There’s a popular belief that once you’ve had a particular strain of the flu, your body’s immune system will protect you against it in the future. And under the right circumstances, that’s true.

 

But human physiology and its immune response is rarely as simple, and straightforward, as that.

 

Our immune systems vary considerably from one person to the next, and within a single individual, can change  radically over time. We’ve also discovered that some flu viruses leave a stronger `imprint’ on our immune system, than others.

 

Both of these factors can influence how strong . . . and how long lasting . . . any acquired immunity to a flu virus might be.

 

Which is one of the reasons why the CDC reminds us to get a flu shot every year, since the immunity from last year’s vaccine (or a bout with the flu) may have diminished over time – even if the same flu strains remain in circulation.

 

Now a study, published today in Journal of Leukocyte Biology, looks at another variable in influenza infection that appears to influence the type, and strength, of the immune response (at least in mice).

 

The initial viral dose.  The study is called:

 

Initial infectious dose dictates the innate, adaptive, and memory responses to influenza in the respiratory tract

Isabelle Marois, Alexandre Cloutier, Émilie Garneau and Martin V. Richter

Abstract

Factors from the virus and the host contribute to influenza virus pathogenicity and to the development of immunity. This study thoroughly examined the effects of an initial infectious dose of virus and unveiled new findings concerning the antiviral and inflammatory responses, innate and adaptive immunity, memory responses, and protection against secondary heterologous infection.

(Continue . . . )

 

In this experiment, researchers infected two groups of mice – one with a low dose and one with a high dose –of influenza A (H3N2), and then gauged various aspects of their immune response. Later, they exposed these mice to a different strain of flu to see what, if any, immune response was `left over’ from the initial infection.

 

As I’ve cautioned before, mouse models are often very useful in laboratory research, but what happens with mice doesn’t always correspond to what happens with human physiology. 

 

Still, they came up with some intriguing results. They found that the larger the initial infectious dose, the greater, broader, and longer-lived was the immune response.

 

The full study is behind a pay wall, but we’ve got a press release (slightly reparagraphed for readability) from the Federation of American Societies for Experimental Biology that provides the broad strokes to this research.

 

Flu immunity is affected by how many viruses actually cause the infection

New research published in the Journal of Leukocyte Biology suggests that the immune response differs depending on the amount of virus received during infection

Bethesda, MD—Not only does the type of flu virus affect a patient's outcome, but a new research report appearing in the Journal of Leukocyte Biology suggests that the number of viruses involved in the initial infection may be important too.

 

Scientists from Canada found that when mice were infected by relatively high concentrations of the flu virus, they not only developed immunity against the virus that infected them, but this also promoted the generation of a type of immune cell in the lungs poised to rapidly react against infections with other strains of the flu, as well.

 

Mice that were infected with a relatively low concentration of the virus developed weaker immunity against the strain that infected them, did not build up this crucial population of immune cells in the lungs, and showed only delayed immunity toward other flu strains.

 

This discovery could pave the way for new prophylactic strategies to fight flu infections and provides a novel basis for vaccine design.

 

"Hopefully, the findings of our study will help to develop better vaccine preparations that will be more effective in inducing protective cellular immunity to fight against infectious pathogens such as bacteria, viruses and fungi," said Martin V. Richter, Ph.D., the lead researcher involved in the work from the Department of Medicine at the Université de Sherbrooke and Centre de Recherche Clinique Étienne-Le Bel in Québec, Canada.

 

(Continue . . . )

 

 

While both are complex and multifaceted, our immune systems can be divided into two types of protection.

 

We have natural immunity – so called `innate immunity’ – that can detect, and launch a generic defense against a wide variety of invading pathogens

 

Were it not for this built-in immunity, none of us would survive past the first few hours or days of life; we'd be quickly overrun by opportunistic infections.

 

Innate immune system buys us time for our Adaptive Immune System to learn to recognize and fight specific pathogens.

 

The adaptive immune system produces pathogen-specific antibodies that can remember previous encounters with a virus, and provides us with varying degrees of acquired immunity.

 

For more information on some of the complexities of our immune system, you may wish to revisit some of these earlier blog posts.

 

 

Study: Vitamin D And The Innate Immune System

GM-CSF: An Innate Ability To Fight Flu

Cytokine Storm Warnings

PAMP and Circumstance

 

And for a fascinating look at the pathogenesis of influenza, the innate immune system, and the role of cytokines I would invite you to read my 3-part look at the Baskin pathogenesis study from 2009.

 

Dissecting the Influenza Pathogenesis Study Pt. 1

Dissecting the Influenza Pathogenesis Study Pt. 2

Dissecting the Influenza Pathogenesis Study Pt. 3

EID Journal: Revisiting The `Canadian Problem’

 

Photo Credit PHIL

# 6267

 

 

In September of 2009, just as the second wave of the H1N1 pandemic was ramping up, news of an unpublished study began to surface in Canada that suggested that those who had received a seasonal flu shot the previous year were more susceptible to the new pandemic virus than those who hadn’t.

 

Helen Branswell, science and medical reporter for the Canadian Press, was among the first to report on it (see Branswell On The Canadian Flu Shot Controversy).

 

 

This bombshell – which began to be known as `the Canadian problem’, sent shockwaves through public health agencies, many of whom were just days away from starting up their seasonal flu vaccination campaigns as they waited for the arrival of the H1N1 pandemic vaccine expected later in the fall.

 

Suddenly, there was genuine concern that with a pandemic virus on the way, that rolling out the seasonal vaccine might be the wrong thing to do.

 

The CDC and the World Health Organization both scrambled to look at their available data, and stated that they could find no correlation between the seasonal vaccine and susceptibility to the pandemic flu . . . but that they would continue to look.

 

Meanwhile, with concerns rising, a number of Canadian Provinces halted or announced delays in their seasonal flu shot campaign, even though the study had yet to be published (see Ontario Adjusts Vaccination Plan).

 

October saw a number of new reports and studies that failed to corroborate the (still unpublished) findings, including a study published in the BMJ (British Medical Journal) that suggested exactly the opposite - that getting the seasonal flu vaccination may be slightly protective against the swine flu  (see When Studies Collide).

 

By November, with no compelling corroboration of the `Canadian Problem’, Canada’s National Advisory Committee on Immunization (NACI) came out in favor of resuming seasonal flu jabs (see NACI: Canada Should Resume Seasonal Flu Vaccinations).

 

The controversy wasn’t over, however.

 

In April of 2010 these Canadian studies were finally published by PLoS Medicine. Writing for CIDRAP, Maryn McKenna   detailed their findings.

 

New Canadian studies suggest seasonal flu shot increased H1N1 risk

Maryn McKenna Contributing Writer

Apr 6, 2010 (CIDRAP News) – Despite a rapidly launched range of studies, investigators in Canada are still unable to say—or to rule out—whether receiving a seasonal flu vaccination in the 2008-09 season made it more likely that Canadians would become ill from 2009 pandemic H1N1 flu.

(Continue . . .)

 

Other studies, however, failed to show any correlation, leaving us with a bit of a mystery on our hands. 

 

Fast forward to today and we’ve another study that appears ahead of print in May’s edition of the CDC’s EID Journal that looks at this supposed link, and once again, finds no evidence to support it.

 

 

Volume 18, Number 5—May 2012

Research

No Association between 2008–09 Influenza Vaccine and Influenza A(H1N1)pdm09 Virus Infection, Manitoba, Canada, 2009

Salaheddin M. Mahmud , Paul Van Caeseele, Gregory Hammond, Carol Kurbis, Tim Hilderman, and Lawrence Elliott

Abstract

We conducted a population-based study in Manitoba, Canada, to investigate whether use of inactivated trivalent influenza vaccine (TIV) during the 2008–09 influenza season was associated with subsequent infection with influenza A(H1N1)pdm09 virus during the first wave of the 2009 pandemic.

 

Data were obtained from a provincewide population-based immunization registry and laboratory-based influenza surveillance system.

 

The test-negative case–control study included 831 case-patients with confirmed influenza A(H1N1)pdm09 virus infection and 2,479 controls, participants with test results negative for influenza A and B viruses. For the association of TIV receipt with influenza A(H1N1)pdm09 virus infection, the fully adjusted odds ratio was 1.0 (95% CI 0.7–1.4). Among case-patients, receipt of 2008–09 TIV was associated with a statistically nonsignificant 49% reduction in risk for hospitalization.

 

In agreement with study findings outside Canada, our study in Manitoba indicates that the 2008–09 TIV neither increased nor decreased the risk for infection with influenza A(H1N1)pdm09 virus.

 

 

While the bulk of studies have shown no causal link between receipt of the seasonal vaccine and contracting the 2009 H1N1 virus, the results have not been 100% in alignment.

 

Leaving us with a bit of a mystery.  Why should some Canadian studies differ from those done elsewhere?

 

One fascinating hypothesis that might explain these disparate findings was proffered back in 2010 in the journal Eurosurveillance.

 

The authors suggested that infection by any influenza (or perhaps, any I-L-I) ramps up the body’s immune system for a time, making that person temporarily less susceptible to infection by another respiratory virus.

 

Since the pandemic arrived on the heels of the flu season in the northern hemisphere, those who received flu shot in the fall and thereby avoided illness might have been more likely to catch the pandemic strain than someone who had endured a bout of flu (and thereby acquired temporary generic immunity) over the winter.

 

You’ll want to read the entire paper, but I’ve included excerpts (reparagraphed for readability) from the abstract below.

 

 

Eurosurveillance, Volume 15, Issue 47, 25 November 2010

Perspectives

Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection

H Kelly , S Barry, K Laurie, G Mercer

ABSTRACT (Excerpts)

We found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus.

 

Ferret experiments have suggested protection against pandemic influenza A(H1N1) 2009 from multiple prior seasonal influenza infections but not from prior seasonal vaccination.Modelling studies suggest that influenza infection leads to heterosubtypic temporary immunity which is initially almost complete.

 

We suggest these observations together can explain the apparent discrepant findings in Canada and Victoria. In Victoria there was no recent prior circulation of seasonal influenza and thus no temporary immunity to pandemic influenza. There was no association of seasonal influenza vaccine with pandemic influenza infection.

 

In Canada seasonal influenza preceded circulation of the pandemic virus. An unvaccinated proportion of the population developed temporary immunity to pandemic influenza from seasonal infection but a proportion of vaccinated members of the population did not get seasonal infection and hence did not develop temporary immunity to pandemic influenza.

 

It may therefore have appeared as if seasonal vaccination increased the risk of infection with pandemic influenza A(H1N1) virus.

 

 

It’s an attractive theory, and it has been suggested that this form of temporary immunity might even help explain why influenza pandemics tend to come in waves.

 

But it’s just a theory.

 

While results from today’s EID study match well with most of those in the literature, the authors warn that:

 

Additional epidemiologic and experimental investigations are needed to clarify the relationship between TIV use and infection with the pandemic strain.

 

Good science takes time.

 

And that means that while the evidence is currently lopsided against there being a link, more research will be needed before the `Canadian Problem’ can be fully and truly resolved.

Eurosurveillance: Older People May Be Susceptible To The H3N2v Virus

 

 

# 6104

 

 

The detection of a new swine H3N2v virus among a handful of people across five states in recent months has sparked concerns that a new influenza virus might be trying to establish a foothold in the human population.

 

Since the infections reported in the 2nd half of 2011 were predominantly among young children, there has been some speculation that those over the age of 20 might have some limited immunity to this strain.

The CDC, in their January 6th MMWR Update: Influenza A (H3N2)v Transmission and Guidelines — Five States, 2011, writes:

 

Limited serologic studies conducted to date indicate that young children have little preexisting immunity to influenza A (H3N2)v viruses. Because the hemagglutinin genes of these viruses are related to human influenza A (H3N2) viruses that circulated in the 1990s, older children and adults might have limited immunity against these viruses

 

Yesterday the Journal Eurosurveillance printed an article called:

 

Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunisation with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010

 

by DM Skowronski, G De Serres, NZ Janjua, JL Gardy, V Gilca, M Dionne, ME Hamelin, C Rhéaume, G Boivin

 

 

As the title might suggest, this isn’t exactly `light’ reading. 

 

Luckily we’ve the talented Helen Branswell to lead us through this medical morass, in her report for the Canadian Press. As with any Branswell article, you would be well served to follow the link and read the whole thing. 

 

Older adults may also be vulnerable to new swine influenza virus, study suggests

By: Helen Branswell, The Canadian Press

 

 

Briefly, the Eurosurveillance study finds indications that acquired immunity carried by adults from exposure to similar viruses that were circulating prior to 1990 may wear off as adults age.

 

Since years when the H3N2 seasonal flu dominates often result in a more severe flu season, any decline in immunity among the elderly elicits concern.

 

Right now, the H3N2v virus hasn’t shown the ability to spread efficiently in the human population, although some human-to-human transmission has occurred. 

 

But over time, it may acquire that ability.

Which is why the CDC is working on a vaccine (see H3N2v Vaccine Trials) for this new strain should the need arise.

 

Meanwhile, with the exception of reports out of Mexico where they are seeing a large number of H1N1 cases, influenza reports in North America and Europe remain well below average for this time of year.

Flu Vaccines & The Temporary Immunity Hypothesis

 

 

# 5359

 

 

Late last week several Australian newspapers carried press reports on concerns expressed by Peter Collignon, a Professor of Infectious Diseases and Microbiology at the Australian National University, on the possibility that getting the seasonal flu shot may have increased the likelihood of contracting the 2009 pandemic strain.

 

Coverage included:

 

Rethink flu vaccine policy, says health expert

Adam Cresswell,

Health Editor From: The Australian March 04, 2011

 

Vaccines may have increased swine flu risk

By Annie Guest: ABC News

 

As you might imagine, these claims have sparked considerable concern and controversy. 

 

Although all of the facts are not in, and the data is – at best – contradictory, this morning I thought we’d take a look at Professor Collignon’s concerns.

 

Ironically, after years of hearing from critics that flu vaccines are ineffective, the problem may be that the seasonal flu vaccine worked too well.

 

First a bit of background.  Regular readers will be somewhat familiar with the following:

 

In the fall of 2009, news of an unpublished Canadian study began to surface that suggested that those who had received a seasonal flu shot the previous year were more likely to contract the new pandemic virus than those who hadn’t.

 

Helen Branswell, science and medical reporter for the Canadian Press, was among the first to report on it (see Branswell On The Canadian Flu Shot Controversy).

 

With many Canadian provinces just days away from starting up their seasonal flu vaccination campaigns while they awaited the arrival of the pandemic vaccine later in the fall, this was a bombshell.

 

Suddenly, there was genuine concern that maybe  . . .  just maybe  . . .  with a pandemic virus on the way, that rolling out the seasonal vaccine was the wrong thing to do. 

 

 

The CDC and the World Health Organization both looked at their data, and issued statements that they could find no correlation between the seasonal vaccination and increased susceptibility to the pandemic flu . . . but that they would continue to look.

 

Meanwhile, with concerns rising, a number of Canadian Provinces halted or announced delays in rolling out the seasonal flu shot, even though the study had yet to be published (see Ontario Adjusts Vaccination Plan).

 

October saw a number of new reports and studies that failed to support the `Canadian problem’, including a study published in the BMJ (British Medical Journal) that suggested exactly the opposite.

 

It postulated that getting the seasonal flu vaccination may have been slightly protective against the swine flu  (see When Studies Collide).

 

This, admittedly, ran contrary to what we’d heard from the CDC, who maintained that the seasonal vaccine was not expected to offer any protection against the novel H1N1 swine flu virus.

 

By November, with no further evidence of the `Canadian Problem’, Canada’s National Advisory Committee on Immunization (NACI) came out in favor of resuming seasonal flu jabs (see NACI: Canada Should Resume Seasonal Flu Vaccinations).

 

The controversy didn’t go away, however.

 

In April of 2010 the Canadian study was finally published by PLoS Medicine. Writing for CIDRAP, Maryn McKenna   detailed their findings.

 

New Canadian studies suggest seasonal flu shot increased H1N1 risk

Maryn McKenna Contributing Writer

Apr 6, 2010 (CIDRAP News) – Despite a rapidly launched range of studies, investigators in Canada are still unable to say—or to rule out—whether receiving a seasonal flu vaccination in the 2008-09 season made it more likely that Canadians would become ill from 2009 pandemic H1N1 flu.

(Continue . . .)

 

 

Other studies, however, failed to show any correlation, leaving us with a bit of a mystery on our hands. 

 

In November of last year, an article appeared in the Eurosurveillance Journal that suggested that contracting seasonal flu (as opposed to being vaccinated against it) temporarily ramped up the body’s immune system against other viruses – and that this protective effect could last months.

 

Eurosurveillance, Volume 15, Issue 47, 25 November 2010

Perspectives

Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection

H Kelly , S Barry, K Laurie, G Mercer

 

Unlike the Canadian researchers, Australian scientists could find no increased susceptibility to the pandemic H1N1 virus among those who had been vaccinated the previous year against seasonal flu.

 

The difference between the two findings, they suggest, comes from three separate factors:

 

• A theory regarding temporary immunity following any influenza infection
• The timing of the arrival of the pandemic virus in Canada
• And the protective effects of seasonal flu vaccination against seasonal - but not pandemic - flu.

 

In Canada, the first wave of the virus arrived on the heels of the 2008-2009 seasonal flu epidemic, which had peaked only 3 months earlier. Australia, however, was nearing the end of their summer, and the peak of their flu season had occurred a full 9 months before.

 

If the temporary immunity theory was correct (`if’ being the operative word), Canadians who had contracted seasonal flu earlier in the year, might still have carried some generic immunity against infection.

 

Australians, on the other hand, saw the pandemic virus arrive long after any such temporary protective benefits would have decayed.

 

This temporary immunity – which some scientists believe may be a linked to the theory of OAS (Original Antigenic Sin) – is not well understood.  Complex, and deserving of a blog of its own, I won’t go into detail on OAS today, since we’ve discussed it before:

 

EID Journal: Original Antigenic Sin And Pandemic H1N1

 

CIDRAP On Original Antigenic Sin

 

 

In December of 2010, in the journal Clinical Infectious Diseases, we saw another study – this time in Hong Kong – that looked at the potential interaction between the 2008 seasonal vaccine, influenza infection, and the 2009 pandemic flu.

 

Protective Efficacy of Seasonal Influenza Vaccination against Seasonal and Pandemic Influenza Virus Infection during 2009 in Hong Kong

Benjamin J. Cowling,Sophia Ng, Edward S. K. Ma, Calvin K. Y. Cheng, Winnie Wai, Vicky J. Fang, Kwok-Hung Chan, Dennis K. M. Ip, Susan S. Chiu,  J. S. Malik Peiris and Gabriel M. Leung

Conclusions. TIV protected against strain-matched infection in children. Seasonal influenza infection appeared to confer cross-protection against pandemic influenza. Whether prior seasonal influenza vaccination affects the risk of infection with the pandemic strain requires additional study.

 

Once again, evidence to suggest that catching the seasonal flu during the winter of 2008-2009 was somewhat protective against contracting the pandemic in the months following.

 

Which brings us back to Professor Collignon, who is suggesting that we should reassess our vaccination policies.

 

He argues that it may be better for healthy adults to get the seasonal flu – and develop more robust temporary immunity against potentially emerging viruses – than to routinely get the flu jab.

 

This is a controversial stance, and one that is not widely shared by researchers, scientists, and public health officials.  

 

Arguing for the seasonal flu vaccine are that even healthy adults can suffer serious illness from influenza, and that any broad viral immunity from contracting seasonal flu is likely short-lived – probably measured in months, not in years.

 

When you add the fact that novel (pandemic) viruses emerge infrequently, the case for getting the annual flu shot grows stronger.  

 

For now, the Temporary Immunity Hypothesis remains an intriguing, but as-yet unproven theory.

 

For those who like their science neat and tidy, devoid of ambiguity, and rock solid . . .  all of this is no doubt a bit disconcerting. But this is how scientific progress works.

 

Slowly, deliberately, and not always advancing in a linear fashion. Simply put, good science takes time.

 

While I find all this quite thought provoking - and absolute truths are always elusive - unless and until more compelling data to the contrary comes forth, I intend to get my flu shot every year.

 

Call it a calculated risk.

 

After all . . .  a pandemic may occur once every couple of decades, but seasonal flu comes around every year.

Of Mice and Men - And The Hygienic Hypothesis

 

 

# 5142

 

 

Note: The `Hygienic Hypothesis’ – while something I personally find fascinating to write about - remains an unproven theory, and so what follows needs to be taken in that light.

 

Similarly, mouse studies, while often useful in medical research, don’t always predict what happens in human physiology.

 

 

In the past several weeks the hygienic hypotheses has made headlines a number of times, something I covered late last month in Study: Bisphenol A, Triclosan and The Hygienic Hypothesis, and Maryn McKenna wrote about here and here.

 

In brief, the `Hygienic Hypothesis’ is a theory that suggests some of the allergies and autoimmune diseases common to modern man come about due to a lack of exposure to certain biological agents (bacteria, viruses, and even parasites)  . . . particularly in early childhood.

 

Research over the past decade has increasingly linked the use of household cleaners (bleach, disinfectants, carpet cleaners, etc) and other chemicals (turpentine, insecticides, etc) to childhood onset asthma and allergies (see MedNews Today Asthma in kids linked to household cleaning products and chemicals).

 

Essentially, the hygienic hypothesis says we may be trying to be `too clean’ for our own good.

 

One of the more controversial aspects of this theory is that intestinal parasites (ie. worms) – which have been largely eliminated in the western world - are actually beneficial, and can help prevent (or even cure) certain types of inflammatory bowel disease.

 

NPR (along with many other media outlets) covered this story at length a couple of weeks ago (see Eat Your Worms: The Upside Of Parasites).

 

Today, a new study appears in the Journal of Clinical Investigation, that lends additional support to the hygienic hypothesis.

 

It looks at the protective effects of certain types of viral infections in suckling mice against adult onset asthma. Before you scoff, this research has a pretty impressive pedigree.

 

A link, and a couple of excerpts from the abstract (follow the link to read it in its entirety) follow:

 

Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity

Ya-Jen Chang, Hye Young Kim, Lee A. Albacker, Hyun Hee Lee, Nicole Baumgarth, Shizuo Akira, Paul B. Savage, Shin Endo, Takashi Yamamura, Janneke Maaskant, Naoki Kitano, Abel Singh, Apoorva Bhatt, Gurdyal S. Besra, Peter van den Elzen, Ben Appelmelk, Richard W. Franck, Guangwu Chen, Rosemarie H. DeKruyff, Michio Shimamura, Petr Illarionov, Dale T. Umetsu

J. Clin. Invest. 2010; doi:10.1172/JCI44845

Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis.

 

Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma.

 

<SNIP>

 

These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.

 

Basically researchers infected 2-week old (suckling) mice and 8-week old (adult) mice with with the A/Mem71 (H3N1) influenza virus. Six weeks later both cohorts were tested for susceptibility to an asthma-like reaction.

 

Mice that were infected at 2-wks of age were protected against an asthma-like reaction.

 

Those infected as adults were not.

 

 

The reason given for this protective effect was an increase in certain types of NKT (natural killer T-cells) in baby mice post-infection, something which was not observed in the influenza-challenged adult mice.

 

Interestingly, the researchers also found that a molecule produced by the stomach bacteria Helicobacter pylori also produced a protective affect against asthma in adult mice, giving hopes for a new avenue of research into better treatments.

 

The article is lengthy, technical, and  open access. I’ve only scratched the bare surface with this overview. Those interested in learning more should follow this link to read the entire study.

 

Before anyone decides to eat worms, stop bathing, or move down to the city sewers for their health . . . remember:

 

The hygienic hypothesis is still just a theory.

Eurosurveillance: The Temporary Immunity Hypothesis

 

 

# 5092

 

 

In September of 2009, news of an (at that time) unpublished Canadian study began to surface that suggested that those who had received a seasonal flu shot the previous year were more susceptible to the new pandemic virus than those who hadn’t.

 

Helen Branswell, science and medical reporter for the Canadian Press, was among the first to report on it (see Branswell On The Canadian Flu Shot Controversy).

 

This bombshell – which began to be known as `the Canadian problem’, sent shockwaves through public health circles.  Many agencies were just days away from starting up their seasonal flu vaccination campaigns as they waited for the arrival of the H1N1 pandemic vaccine expected later in the fall.

 

Suddenly, there was genuine concern that maybe  . . .  just maybe  . . .  with a pandemic virus on the way, that rolling out the seasonal vaccine was the wrong thing to do. 

 

The CDC and the World Health Organization both scrambled to look at their available data, and stated that they could find no correlation between the seasonal vax and susceptibility to the pandemic flu . . . but that they would continue to look.

 

Meanwhile, with concerns rising, a number of Canadian Provinces halted or announced delays in rolling out the seasonal flu shot, even though the study had yet to be published (see Ontario Adjusts Vaccination Plan).

 

October saw a number of new reports and studies that failed to corroborate the (still unpublished) findings, including a study published in the BMJ (British Medical Journal) that suggested exactly the opposite - that getting the seasonal flu vaccination may be slightly protective against the swine flu  (see When Studies Collide).

 

Which, admittedly, ran contrary to what we’d heard previously from the CDC, who maintained that the seasonal vaccine was not expected to offer any protection against the novel H1N1 swine flu virus.

 

By November, with no compelling corroboration of the `Canadian Problem’, Canada’s National Advisory Committee on Immunization (NACI) came out in favor of resuming seasonal flu jabs (see NACI: Canada Should Resume Seasonal Flu Vaccinations).

 

The controversy wasn’t over, however.

 

In April of this year these Canadian studies were finally published by PLoS Medicine. Writing for CIDRAP, Maryn McKenna   detailed their findings.

 

New Canadian studies suggest seasonal flu shot increased H1N1 risk

Maryn McKenna Contributing Writer

Apr 6, 2010 (CIDRAP News) – Despite a rapidly launched range of studies, investigators in Canada are still unable to say—or to rule out—whether receiving a seasonal flu vaccination in the 2008-09 season made it more likely that Canadians would become ill from 2009 pandemic H1N1 flu.

(Continue . . .)

 

Other studies continued to fail to show any correlation, leaving us with a bit of a mystery on our hands. 

 

Why were these Canadian findings so different than all the others?

 

Which bring us to today’s story regarding a hypothesis that appeared in yesterday’s Eurosurveillance journal, suggesting a mechanism that might explain the `Canadian Problem’.

Eurosurveillance, Volume 15, Issue 47, 25 November 2010

Perspectives

Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection

H Kelly , S Barry, K Laurie, G Mercer

 

You’ll probably want to read the entire paper, but for those not inclined to wade through the whole article, I’ll attempt to summarize their hypothesis.

 

Unlike the Canadian researchers, Australian scientists could find no increased susceptibility to the pandemic H1N1 virus among those who had been vaccinated the previous year against seasonal flu.

 

The difference between the two findings, they suggest, comes from three separate factors:

• A theory regarding temporary immunity following any influenza infection
• The timing of the arrival of the pandemic virus in Canada
• And the protective effects of seasonal flu vaccination against seasonal - but not pandemic - flu.

 

We’ll take these one at a time.

 

It has been theorized that infection by any influenza (or perhaps, any respiratory) virus ramps up the body’s immune system for weeks or even months after the illness has passed, making that person temporarily less susceptible to infection by another virus.

 

Researchers, looking back at the infection patterns from the 1918 and 1957 pandemics, have used this theory to explain why pandemics come in waves.

 

And given that each year we usually see two A strains of influenza, a B strain, and a veritable rogues gallery non-influenza respiratory viruses circulating, this may also help explain why we all don’t endure non-stop ILI’s every winter.

 

Which bring us to the timing element.

 

In Canada, the first wave of the virus arrived on the heels of the 2008-2009 seasonal flu epidemic, which had peaked only 3 months earlier.

 

Australia, however, was nearing the end of their summer, and the peak of their flu season had occurred a full 9 months before.

 

If the temporary immunity theory is correct (`if’ being the operative word), Canadians who had contracted seasonal flu earlier in the year, may still have carried some generic immunity against infection.

 

Australians, on the other hand, saw the pandemic virus arrive long after any such temporary protective benefits would have decayed.

The third element is the protective benefits of the seasonal flu vaccine. 

 

The 2008-2009 vaccine was reasonably protective against seasonal flu, but offered little or no protection against the novel H1N1 virus.

 

Since those that eschewed the seasonal vaccine were more likely to catch the flu, it increased their opportunity to develop the (hypothesized) temporary generic immunity discussed above. 

 

The authors suggest that those who took the vaccine, lacking the `temporary protection’ from a recent bout with the flu, may have appeared to be more susceptible to the pandemic virus.

 

It’s an attractive solution, and many of the elements do seem to fit. 

 

But to make it work, you have to accept the temporary immunity hypothesis as being valid - and while gaining acceptance – it hasn’t been fully proven.

 

And if this explanation is correct, you would also expect to find a similar pattern in other vaccinated regions of the northern hemisphere where novel H1N1 arrived shortly after the peak of their flu season. 

 

So far, that hasn’t been demonstrated.

 

But good science takes time, which means that more research will be needed on several fronts before this theory can be accepted as a resolution to the `Canadian Problem’.

Study: Eurosurveillance On `The Canadian Problem’

 

 

# 4728

 

 

It was called, euphemistically, the `Canadian Problem’.

 

News of a controversial, yet unpublished, Canadian study that began to emerge last September suggesting those who had received a seasonal flu shot in the previous year were more susceptible to the pandemic H1N1 virus.

 

Helen Branswell, science and medical reporter for the Canadian Press, was among the first to report on it (see Branswell On The Canadian Flu Shot Controversy).

 

 

In a matter of days a number of Canadian Provinces halted or announced delays in rolling out the seasonal flu shot, even though the study had yet to be published (see Ontario Adjusts Vaccination Plan).

 

The CDC and the World Health Organization, meanwhile, stated they saw no evidence in their data to suggest a link, but that they were continuing to investigate the matter.

 

Since then we’ve seen conflicting information.

 

In early October we saw  a study published in the BMJ (British Medical Journal) that suggested exactly the opposite - that getting the seasonal flu vaccination may be slightly protective against the swine flu  (see When Studies Collide).

 

Which, admittedly, ran contrary to what we’d heard previously from the CDC, who maintained that the seasonal vaccine was not expected to offer any protection against the novel H1N1 swine flu virus.

 

By November, with no compelling corroboration of the `Canadian Problem’, Canada’s National Advisory Committee on Immunization (NACI) came out in favor of resuming seasonal flu jabs (see NACI: Canada Should Resume Seasonal Flu Vaccinations).

 

In April, writing for CIDRAP, Maryn McKenna wrote of the publication of these four controversial studies in PLoS Medicine.

 

 

New Canadian studies suggest seasonal flu shot increased H1N1 risk

Maryn McKenna Contributing Writer

Apr 6, 2010 (CIDRAP News) – Despite a rapidly launched range of studies, investigators in Canada are still unable to say—or to rule out—whether receiving a seasonal flu vaccination in the 2008-09 season made it more likely that Canadians would become ill from 2009 pandemic H1N1 flu.

(Continue . . .)

 

 

Which brings us, today, to a newly published study in Eurosurveillance on a household study conducted in Australia on the very issue.

 

A hat tip to Ironorehopper on FluTrackers for posting this link.

 

 

Eurosurveillance, Volume 15, Issue 28, 15 July 2010

Rapid communications

Association between 2009 seasonal influenza vaccine and influenza-like illness during the 2009 pandemic: preliminary results of a large household transmission study in Western Australia

D Carcione, C Giele, L S Goggin, K S Kwan, D W Smith, G K Dowse, D B Mak, P Effler

---

We conducted a prospective household transmission study to examine whether receipt of 2009 trivalent influenza vaccine (TIV) was associated with increased risk of influenza-like illness (ILI) among contacts of confirmed pandemic influenza A(H1N1) 2009 patients.

 

In the week following onset of pandemic illness in a household member, 46 (15%) of 304 TIV-vaccinated contacts, and 174 (15%) of 1,162 unvaccinated contacts developed ILI (p= 0.95).

 

Receipt of 2009 TIV had no effect on one’s risk of pandemic illness.

 

 

Although one would hope for a definitive, etched-in-stone answer here, as always there are limitations to this study.    In the author’s discussion, they write:

 

 

Several limitations of our study should be noted. First, the outcome sought was clinical ILI and not laboratory-proven influenza. Only a small subset of household contacts who developed ILI were tested for influenza; however, a high proportion of the contacts tested by PCR within two days of developing ILI were confirmed as having pandemic influenza A(H1N1) 2009 infection.

 

Second, vaccination histories were not verified through medical records. Most seasonal 2009 TIV vaccinations would have been administered between the months of March and June 2009, and interviews to determine vaccination status were conducted between late May and early August 2009. Whilst errors in recall may have occurred, it seems reasonable to assume that were this the case such errors would be similar among the cohort who later developed ILI, compared to those who did not.

 

While this study did not find an association – either positive or negative – to prior inoculation and contracting novel H1N1, the authors regard this as an interim analysis.

 

No doubt, this is a subject that will command additional study and analysis.  For now, however, if there is an association . . . it doesn’t appear to be pervasive.

NIAID: 2009 H1N1 Vaccine Protects Mice Against 1918 Flu Virus

 

 

# 4949

 

 

For quite some time we’ve recognized that many of those born before – say, 1957 – have some level of immunity against the 2009 H1N1 pandemic virus.  The belief has been that those who were around in the 1940s and 1950s were exposed to a similar virus.

Last August, we learned of research out of Vanderbilt University, that showed that survivors of the 1918 pandemic still retained antibodies against that virus, and that they were protective against the 2009 pandemic virus.

 

 

Survivors of 1918 Flu Pandemic Immune 90 Years Later

By Steven Reinberg

Monday, August 18, 2008; 12:00 AM

SUNDAY, Aug. 17 (HealthDay News) -- People who lived through the 1918 flu pandemic that killed 50 million worldwide are still producing antibodies to the virus 90 years later, researchers report.

(Continue . . . )

 

 

Now scientists working with mice and the 1918 Spanish Flu virus have discovered that this cross-protection works both ways – that the vaccine developed against the 2009 virus is protective (in mice, anyway) against the Spanish flu virus.

 

While vaccines against the 2007 strain of seasonal H1N1 provided some immunity, unvaccinated mice and mice only vaccinated against H3N2 all died when challenged by the 1918 virus.

Mice vaccinated against the 2009 pandemic H1N1 all survived that challenge. 

 

This press release appears to builds on similar research described in another press release by the NIH last March entitled 1918 and 2009 Pandemic Influenza Viruses Lack a Sugar Topping.

 

Here is the NIAID press release (slightly reformatted for readability)

 

 
NIH-Funded Scientists Find 2009 H1N1 Pandemic Influenza Vaccine Protects Mice from 1918 Influenza Virus

WHAT:  
Mice injected with a 2009 H1N1 pandemic influenza vaccine and then exposed to high levels of the virus responsible for the 1918 influenza pandemic do not get sick or die, report scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

 

The new vaccine works against the old virus because the 1918 and the 2009 strains of H1N1 influenza share features that allow vaccine-generated antibodies to recognize both viruses.

 

To learn more, similar challenge studies need to be conducted in other animals, including monkeys, but the investigators say their results suggest people who are vaccinated against 2009 H1N1 influenza or were exposed to the virus could have similarly cross-protective antibodies against the 1918 strain of H1N1.

 

This finding, they add, should help allay concerns about the potential consequences of an accidental release of the 1918 influenza virus from high-containment laboratories or its possible use as a bioterror weapon.

 

Adolfo Garcia-Sastre, Ph.D., of Mount Sinai School of Medicine, New York, led the research. Groups of mice were exposed to lethal amounts of the 1918 influenza virus 14 or 28 days after receiving a 2009 H1N1 influenza vaccine; a seasonal H3N2 influenza vaccine (not designed to protect against H1N1 virus); or no vaccine.

 

All of the 2009-H1N1-vaccinated mice survived. Unvaccinated mice and mice that received the H3N2 vaccine all died. (A group of mice vaccinated with a seasonal flu vaccine designed to protect against a 2007 strain of H1N1 were mostly protected from lethal challenge; 80 percent of the mice in that group survived.)

 

The researchers also injected mice with blood serum taken from people who had received 2009 H1N1 influenza vaccine. The serum, which contained antibodies against 2009 H1N1 influenza virus, protected the mice from death when they were later exposed to the 1918 H1N1 influenza virus. All the experiments involving the 1918 virus were conducted under biosafety-level-3 conditions.

(Continue . . . )

 

Study: Prior Immunity And Pandemic Waves

 

 

# 4595

 

 

One of the great mysteries about influenza pandemics is why illness seems to come in waves, sometimes separated by months with little or no flu activity. 

 

The 1918 pandemic appeared in many regions as three separate waves.  A milder wave during the spring and summer of 1918, followed by an intense and very deadly wave in the fall, and  a return of the following spring. 

 

The progression of the Spanish Flu in the UK, in 1918-1919.

 

Again in 1957, and in 1968, we saw pandemic influenza come in repeated waves, but the exact reason why the virus should flare, infect some – but not all – then recede for months only to return,  has never been adequately explained.

 

Today from BMC Infectious Diseases we get this open access research articles where the authors postulate that pre-existing immunity from exposure to previous influenza’s may have been partially protective to selected (largely urban) populations during the 1918 pandemic, which may help explain the wave phenomenon.

 

Here is the abstract, and this link will take you to the provisional PDF. 

 

 

 

Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

John D Mathews , Emma S McBryde , Jodie McVernon , Paul K Pallaghy  and James M McCaw

BMC Infectious Diseases 2010, 10:128doi:10.1186/1471-2334-10-128

Published:
25 May 2010

Abstract (provisional)

Background

The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?

Methods

We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.

Results

Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R0 credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).

Conclusions

Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza.

 

Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.

An Unexpected Dividend

 

 

# 4522

 

 

Long ago, and in a galaxy far, far away . . . I was part of a national effort to immunize the country against a feared swine flu pandemic.  The year was 1976, and after a disastrous vaccination campaign that saw 40 million Americans get vaccinated, the pandemic (thankfully) never materialized.

 

I’ve written about those events several times, including Deja Flu, All Over Again.

 

 

Now it seems that the much-maligned swine flu vaccination of 1976 may be responsible for an enhanced immune response in some individuals against the 2009 novel H1N1 virus.

 

This press release from St. Jude Children’s Research Hospital.

 

Study Links 1976 'Swine Flu' Shot to Stronger Immune Response to 21st Century Pandemic Flu

St. Jude Children's Research Hospital staff helps investigators gauge the lingering impact of the 1976 vaccine

MEMPHIS, Tenn., April 23 /PRNewswire-USNewswire/ -- New evidence shows immunization against "swine flu" in 1976 might provide individuals with some protection against the 2009 pandemic H1N1 influenza virus, according to new research from St. Jude investigators.

 

Researchers found that individuals who reported receiving the 1976 vaccine mounted an enhanced immune response against both the 2009 pandemic H1N1 virus and a different H1N1 flu strain that circulated during the 2008-09 flu season. The work appears in the April 23 online issue of the journal Clinical Infectious Diseases.

 

"Our research shows that while immunity among those vaccinated in 1976 has waned somewhat, they mounted a much stronger immune response against the current pandemic H1N1 strain than others who did not receive the 1976 vaccine," said Jonathan A. McCullers, M.D., an associate member of the St. Jude Infectious Diseases Department and the study's lead author.

 

McCullers said it is unclear if the response was enough to protect against the 2009 H1N1 virus, but the study points to a lingering benefit. The findings also raise hope that those vaccinated against the 2009 H1N1 pandemic strain might also enjoy a similar long-term advantage.

(Continue . . . )

Referral: Effect Measure On The JAMA Herd Immunity Study

 

 

 

# 4420

 

 

This morning Revere over at Effect Measure takes a long look though epidemiologist’s eyes at the recently published study on childhood flu vaccinations and community `herd immunity’.

 

More importantly, he looks at some of the myriad difficulties involved in conducting randomized controlled trials (RCTs).

 

It’s a fascinating read.  Highly recommended.

 

Flu vaccines, herd immunity and randomized trials

Study: Protective Immune Memory In Healthy Adults

 

 

# 4022

 

One of the ongoing mysteries surrounding the H1N1 pandemic is why some older adults seem to have limited immunity to this virus, while many younger adults and children do not.

This has obviously sparked a good deal of investigation over the past 6 months, and in recent weeks we’ve seen a number of studies supporting the notion that some older people may have a degree of limited pre-existing immunity to this virus.

 

For some people that may mean they will be able to fight off infection completely, and for others it may mean they suffer lesser symptoms, or recover sooner, than they might otherwise.

None of this is a guarantee, of course.  But the relative risk of infection does seem to go down with age.  

 

 

Last week, in a blog entitled, NEJM: Boomers Have More Immunity I wrote about a short, and pretty straight forward letter to the NEJM, by David N. Fisman, M.D., M.P.H. at the University of Toronto  who wrote about the limited immunity that those over the age of 53 appear to have to the H1N1 pandemic virus.

 

His conclusion?

 

Those born between 1957 and 1975 appear to have less immunity than the boomer generation, but more than those born after 1975. 

 

Older Age and a Reduced Likelihood of 2009 H1N1 Virus Infection

Volume 361:2000-2001 November 12, 2009 Number 20

 

And a month ago, I blogged about Two H1N1 Immunity Studies from the EID Journal, that hypothesized that over time exposure to other circulating influenza strains – or perhaps repeated seasonal flu vaccinations – may have helped to provoke a limited immune response in some people to this novel pandemic strain.

 

Preexisting Immunity to Pandemic (H1N1) 2009
Z. Xing and C.J. Cardona  (186 KB, 5 pages)

 

Serologic Survey of Pandemic (H1N1) 2009 Virus, Guangxi Province, China H. Chen et al.  (155 KB, 4 pages)

 

Today, we get word of another study, this time from La Jolla Institute for Allergy and Immunology, Calif. and NIAID, that finds that older people who have been exposed to previous influenzas may have picked up some limited protective immune memory.

 

 

National Institute of Allergy and
Infectious Diseases (NIAID)
http://www.niaid.nih.gov

FOR IMMEDIATE RELEASE
Monday, Nov. 16, 2009

 
Immune System of Healthy Adults May Be Better Prepared Than Expected to Fight 2009 H1N1 Influenza Virus

WHAT:

A new study shows that molecular similarities exist between the 2009 H1N1 influenza virus and other strains of seasonal H1N1 virus that have been circulating in the population since 1988. These results suggest that healthy adults may have a level of protective immune memory that can blunt the severity of infection caused by the 2009 H1N1 influenza virus.

 

The study team was led by Bjoern Peters, Ph.D., and Alessandro Sette, Ph.D., of La Jolla Institute for Allergy and Immunology, Calif., grantees of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

 

 

The investigators looked at molecular structures known to be recognized by the immune system—called epitopes—on 2009 H1N1 influenza and seasonal H1N1 viruses. Viral epitopes are recognized by immune cells called B and T cells: B cells make antibodies that can bind to viruses, blocking infection, and T cells help to eliminate virus-infected cells.

 

Using data gathered and reviewed from the scientific literature and deposited into the NIAID-supported Immune Epitope Database and Analysis Resource (www.iedb.org), the investigators found that some viral epitopes are identical in both the 2009 and seasonal H1N1 viral strains. Those epitopes that could be recognized by two subsets of T cells, called CD4 and CD8 T cells, are 41 percent and 69 percent identical, respectively. Subsequent experiments using blood samples taken from healthy adults demonstrated that this level of T-cell epitope conservation may provide some protection and lessen flu severity in healthy adults infected with the 2009 H1N1 influenza virus.

 

Analysis of the database also found that among six viral surface epitopes that can bind antibody, thereby preventing infection, only one is conserved between 2009 and seasonal H1N1 viral strains.

 

These results suggest that healthy individuals may have immune memory that recognizes the 2009 H1N1 strain and therefore can mount some measure of an immune attack. The findings also may help explain why the 2009 H1N1 influenza pandemic affects young children more severely than it does healthy older adults and also why two H1N1 vaccinations are needed to protect children ages nine years and under.

ARTICLE:

J Greenbaum et al. Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human populace. Proceedings of National Academy of Sciences. DOI: 10.1073/PNAS.0911580106.