Showing posts with label antibodies. Show all posts
Showing posts with label antibodies. Show all posts

Tuesday, March 31, 2015

JVI: Investigating Dromedary Immune Serum As MERS-CoV Treatment

Photo: ©FAO/Ami Vitale

Credit FAO


# 9889

 

 

We’ve a study, published  in the Journal of Virology (JVI), that uses the mouse model to explore the possibility of using camel antibodies as a treatment option for MERS-Cov infection.

 

As we discussed last year in MERS-CoV: The Long Road To A Pharmacological Solution, with no coronavirus-specific therapy in our arsenal, treatment for infection has basically been supportive (e.g. fluids, vasopressors, ventilators and/or ECMO, dialysis, and antibiotics for secondary infections).

 

We’ve seen some limited testing of Ribavirin & Interferon Treatment of MERS-CoV, but he results from treating humans with this drug combo were far from encouraging.  Other drugs are under investigation, like Biocryst’s experimental antiviral BCX4430, but  it is too early to know how effective it might be.

 

The therapeutic option with perhaps the most promising future is the use of Convalescent Plasma, taken from patients who have already recovered from infection, but here again, there have been roadblocks, Many MERS survivors – due to advanced age, general health, or low antibody titers – are poor donors.

 

The idea of using convalescent serum for MERS goes back nearly two years; This is from the World Health Organization Novel coronavirus summary and literature update – as of 8 May 2013.

An international network of clinical experts has been convened to discuss therapeutic options. It concluded that in the absence of clinical evidence for disease-specific interventions, convalescent plasma is the most promising therapy. A memo containing advice for setting up international or regional serum centers, to obtain and share convalescent plasma, has been circulated by WHO to ministries of health in affected countries. WHO and the International Severe Acute Respiratory and Emerging Infection Consortium have developed and shared a set of research protocols and case report forms to help clinical investigators establish studies of pathogenesis and pharmacology. These are available at http://www.prognosis.org/isaric/.

 

Making headlines last year, and sparking a great deal of Arabic twitter traffic,  was talk that serum antibodies might be harvested from camels, along with camel milk immune proteins, and then used to treat human infections.


It is not that far-fetched, as horse serums have been used for treating humans for more than a century, although their use has declined in recent years due to concerns over adverse reactions and other available options.

 

As nearly all adult camels in Saudi Arabia have been infected with MERS-CoV, they carry specific antibodies against the virus (see Lancet: Camels Found With Antibodies To MERS-CoV-Like Virus), and could theoretically be an abundant source for convalescent serum.

 

Fast forward to today, and we have a study in the Journal of Virology (JVI)  and an accompanying press release, that looks at using dromedary convalescent plasma to treat (or protect against) MERS-CoV infection in mice.


Mice are not a perfect analog for humans, and normally are not even susceptible to the MERS virus (nor are most lab animals, including non-human primates, making studies difficult).  Transgenic mice, however, can be rendered susceptible to the virus, and this study found that camel sera was shown to be protective against a MERS-CoV challenge.

 

The caveat being that what works on mice may not necessarily work in humans. 

 

But as a `proof of concept’  this is a pretty good start.   Follow the link to the study, and the press release below: 

 

Passive Immunotherapy With Dromedary Immune Serum In An Experimental Animal Model For MERS Coronavirus Infection.

Jincun Zhao1, Ranawaka A.P.M. Perera2, Ghazi Kayali3, David Meyerholz4, Stanley Perlman1* and Malik Peiris2*

ABSTRACT

The Middle East Respiratory Syndrome (MERS) is a highly lethal pulmonary infection. Sera from MERS convalescent patients may provide some benefit but is not readily available. In contrast, nearly all camels in the Middle East were previously infected with MERS-CoV. Here, we show that sera obtained from MERS immune camels augment the kinetics of MERS-CoV clearance, and reduce the severity of pathological changes in infected lungs, with efficacy proportional to MERS-CoV neutralizing serum antibody titers.

 

 

Could antibodies from camels protect humans from MERS?

American Society for Microbiology

Antibodies from dromedary camels protected uninfected mice from Middle East Respiratory Syndrome (MERS), and helped infected mice expunge the disease, according to a study published online March 18th in the Journal of Virology, a journal published by the American Society for Microbiology. MERS, which emerged in humans last year in the Saudi Arabian peninsula, causes severe respiratory disease, with a high mortality rate of 35-40 percent. No specific therapy is currently available.

"Our results suggest that these antibodies might prove therapeutic for MERS patients, and might protect uninfected household members and healthcare workers against MERS," says corresponding author Stanley Perlman, MD, PhD, a professor in the Departments of Microbiology and Pediatrics, the University of Iowa, Iowa City.

Passive immunization, a procedure where you inject a former patient's antibodies into a new patient to fight the disease, has been used in the past, including last year in a small number of cases of Ebola, but in the case of MERS, few former patients are available to donate antibodies. Additionally, their antibody titers are often too low, and many former patients are not healthy enough to donate.

Suspecting that humans and dromedaries were likely infected by the same virus, first author Malik Peiris, D. Phil., Professor of Medical Science, School of Public Health, the University of Hong Kong, SAR, China suggested that camel sera might be used to combat MERS. The vast majority of dromedaries on the Arabian peninsula are infected, and many have high antibody titers. The investigators decided to test dromedary antibodies against virus taken from humans. They tested the antibodies in mouse models infected with the latter virus.

 (Continue . . .)

Monday, July 28, 2014

BMC: Decline Of Antibody Titers With A(H1N1)pdm Over Time

image

Credit NIAID

 

 

# 8875

 

The arrival of a novel H1N1 influenza pandemic virus in 2009 – the first one in more than 40 years – has provided researchers with unique opportunities to observe how a newly introduced flu virus behaves in humans, and quite frankly, in other species as well (see The 2009 H1N1 Virus Expands Its Host Range (Again)).

 

Serological studies that would have been impractical before on H3N2 or the old seasonal H1N1 virus – due to decades of ongoing exposure to these strains – suddenly became possible with a new flu in town.

 

One of the unanswered questions surrounding our immune response to influenza infection is how long does our acquired immunity last?  

 

Admittedly, the answer to that question will vary from one person to the next, and depend on a variety of factors including the strain of flu, the person’s age, general health, and state of their immune system.  And there seems to be a difference between the duration of immunity gained from actual infection vs. through vaccination.

 

Despite circulating now for more than 5 years, the (now seasonal) H1N1 virus remains antigenically very similar to the pandemic strain that emerged in the spring of 2009.  So much so that an an A/California/7/2009 (H1N1)pdm09-like virus will be used for the sixth year running in the flu vaccine. 


Yet, despite having a half of decade of vaccination and natural exposure to this new H1N1 virus, last year saw a particularly heavy H1N1 flu season in North America. Normally, we’d look to antigenic drift to explain a major resurgence of a seasonal flu virus after several years, but H1N1 has been remarkably (albeit, not totally) stable in that regard.

   

Drift is the standard evolutionary path of influenza viruses, and comes about due to replication errors that are common with single-strand RNA viruses (see NIAID Video: Antigenic Drift) Drift is primarily responsible for the need to change flu vaccine strains every couple of years (something that is yet to happen with H1N1).

 

Another possibility is waning immunity, something that is recognized (particularly with vaccines, and among the elderly), but has been difficult to quantify in the past.  Given the immune system’s tabula rasa with regards to the 2009 H1N1 virus, it has become possible to track the decline of antibody titers of a cohort of individuals who were first exposed five years ago.

 

Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore

Jung Pu Hsu, Xiahong Zhao, Mark I-Cheng, Alex R Cook, Vernon Lee, Wei Yen Lim, Linda Tan, Ian G Barr, Lili Jiang, Chyi Lin Tan, Meng Chee Phoon, Lin Cui, Raymond Lin, Yee Sin Leo and Vincent T Chow

BMC Infectious Diseases 2014, 14:414  doi:10.1186/1471-2334-14-414

Published: 28 July 2014

Abstract (provisional)

Background

The rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain.

Methods

We followed up a cohort who seroconverted on hemagglutination inhibition (HI) antibody titers (>=4-fold increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in 2009. Along with the pre-epidemic sample, and the sample from 2009 with the highest HI titer between August and October 2009 (A), two additional blood samples obtained in April 2010 and September 2010 (B and C) were assayed for antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays. We analyzed pair-wise mean-fold change in titers and the proportion with HI titers >= 40 and MN >= 160 (which correlated with a HI titer of 40 in our assays) at the 3 time-points following seroconversion.

Results

A total of 67 participants contributed 3 samples each. From the highest HI titer in 2009 to the last sample in 2010, 2 participants showed increase in titers (by HI and MN), while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively.

Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects had titers of >= 40 and >= 160 by HI and MN in 2009, these percentages decreased to 13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the decrease was significantly greater than in those aged below 55, so that none of the elderly had HI titers >= 40 nor MN titers >= 160 by the final sample.

Due to this decline in titers, only 23 (35%) of the 65 participants who seroconverted on HI in sample A were found to seroconvert between the pre-epidemic sample and sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A.

Conclusions

We observed marked reduction in titers 1 year after seroconversion by HI, and to a lesser extent by MN. Our findings have implications for re-infections, recurrent epidemics, vaccination strategies, and for cohort studies measuring infection rates by seroconversion.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

 

The entire study is available, and well worth reading, but I’ve excerpted two paragraphs below that sum up their findings.  

Discussion


The objective of our study was to understand temporal changes in antibody titers following seroconversion during the initial epidemic of A(H1N1)pdm09 infections in  Singapore. Our results revealed a fairly rapid decline in antibody titers following seroconversion, with only a fifth of those who originally had HI titers of  ≥40 and half of those with MN titers of  ≥160 still  having  titers  above  the  respective  cut-off  points  after  a  year.  There  was  also  some indication  that  the  rate  of  decline  was  higher  in  older  individuals,  and  that  the  change  in antibody  titers  measured  by  HI  was  greater  than  by  MN.  Symptomatic  infections  were associated with higher starting antibody titers, and continued to have marginally higher titers in subsequent samples, at least by MN assays.


<SNIP>

Conclusions


Six  months  and  one  year  after  antibodies  peaked  following  presumptive  infection  with A(H1N1)pdm09, only 25% and 14% of participants respectively had antibody  titers against A(H1N1)pdm09 that would be considered protective (HI titer ≥40). The decline in antibody titers may explain susceptibility to re-infections, and recurrent epidemics following the initial epidemic of infections during the pandemic. It also suggests that influenza vaccination may have to be administered more frequently in the tropics where there is year-round circulation of influenza viruses. The rate of decline in elderly individuals may be even more rapid, and if our  findings  are  confirmed,  may  necessitate  alternative  strategies  of  influenza  vaccine development for this vulnerable group.

 

 

A pretty good reminder that even if you got the vaccine last year – or worse, endured the flu last winter – you may not be carrying sufficient immunity forward into the new flu season to protect you against re-infection. 

 

And given that H3N2, and two lineages of Influenza B, are also in circulation – your risks of catching some kind of flu are compounded further.

 

Which is why, even though the H1N1 component of the flu vaccine remains unchanged this year, it is a good idea to get the flu vaccine every year.  

 

Despite variable and sometimes disappointing VE (Vaccine Effectiveness) numbers (see CIDRAP: A Comprehensive Flu Vaccine Effectiveness Meta-Analysis) - particularly among the elderly (see BMC Infectious Diseases: Waning Flu Vaccine Protection In the Elderly) - we continue to see evidence of substantial benefit from the flu shot.

 

For more, you may wish to revisit:

 

CDC: Flu Shots Reduce Hospitalizations In The Elderly
Research: Low Vaccination Rates Among 2013-2014 ICU Flu Admissions
Two Studies On The 2009 Pandemic Flu Vaccine & Pregnancy

Tuesday, April 29, 2014

CIDRAP:Two MERS Antibody Studies

Coronavirus

Photo Credit NIAID

 

 

# 8546

 

 

Last night CIDRAP News published a report by Lisa Schnirring on a pair of human antibody studies released yesterday looking at potential treatments for the MERS coronavirus.  The studies appear in Science Translational Medicine and PNAS, and Lisa does a terrific job summarizing them.

 

Two MERS antibody studies may help quest for treatment

Lisa Schnirring | Staff Writer | CIDRAP News

|

Apr 28, 2014

Amid a surge of MERS-CoV (Middle East respiratory syndrome coronavirus) cases, two research teams today—one based at Harvard University and the other in China—said they have identified antibodies against the novel virus, the first of many steps toward developing a treatment against the disease.

 

The two teams used different search strategies and identified different types of antibodies, but their target was the same: preventing the spike-shaped protein on the surface of MERS-CoV from binding to receptors on the surface of cells that line human airways.

 

MERS-CoV causes a respiratory infection that can lead to severe pneumonia and kidney failure. The disease is fatal for more than 40% of patients infected, and so far there is no treatment or vaccine.

(Continue . . . )

 


Although promising, as Lisa explained, the identification of potentially useful antibodies against the MERS coronavirus is but the first step towards creating a usable therapy.  Over the past 5 years we’ve looked at several similar studies, including:

 

 

These monoclonal antibodies would not work like a vaccine, which confer relatively long-term protection.  Rather, a single injection is expected to serve as a treatment, or to work as a temporary (several week) prophylaxis.

 

While a hugely promising field of research, the above examples show that isolating a candidate antibody is a long way from having a tested and approved therapy. 

 

We’ve seen  a great deal of optimism expressed by the Saudi government about rapidly developing a vaccine for the MERS coronavirus. While no doubt reassuring to the public, a vaccine is something that most scientist believe will take several years to develop (see Obstacles To A MERS Vaccine). 

 

Although a human antibody therapy might be brought to market sooner, no one should expect they will provide a near-term solution to the MERS problem either.

Tuesday, May 21, 2013

Study: Population-Level Antibody Estimates To H7N9

 

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# 7302

 

An open access study recently published in the Journal of Infectious Disease analyzes serum samples gathered from 1723 individuals from Southern Vietnam between 2010-2012.

 

Researchers checked them for IgG antibodies to the HA1 region of 5 avian flu viruses and 11 human flu viruses.

 

While not testing directly against the H7N9 virus - (they used the 2003 H7N7 virus from the Netherlands which has an HA that is a 96% match for the HA of the emerging H7N9) - this antigen would reasonably be expected to produce a significant serological cross reaction to H7N9 antibodies.

 

 

It’s a fascinating study and you’ll probably want to read it in its entirety. I’ve a link to the study, excerpts from abstract, then close with some excepts from the press release.

 

 

Population-level antibody estimates to novel influenza A/H7N9

Maciej F Boni, Nguyen Van Vinh Chau, Nguyen Dong, Stacy Todd, Nguyen Thi Duy Nhat, Erwin de Bruin, Janko van Beek, Nguyen Tran Hien, Cameron P Simmons, Jeremy Farrar, Marion Koopmans

Abstract

There are no contemporary data available describing human immunity to novel influenza A/H7N9. Using 1723 prospectively collected serum samples in southern Vietnam, we tested for antibodies to five avian influenza antigens using a protein microarray.

 

General-population antibody titers against subtype H7 virus are higher than antibody titers against subtype H5, and lower than titers against H9. The highest titers were observed for human influenza subtypes. Titers to avian influenza antigens increased with age and with geometric mean antibody titer to human influenza antigens. There were no titer differences between the urban and the rural location in our study.

 

This study checked for antibodies to 3 different H5 viruses, the H7 virus noted above, and the H9N2 virus – which is not only ubiquitous in poultry across much of Asia, but has also contributed the internal genes to both H5N1 and the H7N9 virus.

 

The entire study is available, and it includes a good deal of discussion of the methods, limitations to this type of antibody analysis, and results obtained. 


The authors found that antibody titers increased with age for all avian flu antigens, as they did with human flu strains. 

 

Their assumption is that exposure to avian strains is likely low, and these results are more likely due to the cross-reactivity of antibodies from past infections with human flu strains. 

 

 

Jumping to the end, the authors write.

 

Population-level immunity appears to be low to influenza A/H7N9 and comparable to what we observe for other avian influenza viruses. In southern Vietnam, we do not see evidence that the current H7N9 outbreaks represent a tip-of-the-iceberg observation of widespread H7N9 infection.

 

We observed no differences between two areas with low and high levels of domestic poultry ownership, indicating that poultry ownership does not have an effect on avian influenza exposure or avian influenza antibody levels. If the H7N9 outbreaks develop into a human transmissible epidemic, the current results will serve as a baseline for interpreting population level serology after the first wave of infections.

 

For more on this Welcome Trust has a press release which provides more background and context for this study.

 

Wellcome Trust

Estimates reveal low population immunity to new bird flu virus H7N9 in humans

The level of immunity to the recently circulating H7N9 influenza virus in an urban and rural population in Vietnam is very low, according to the first population level study to examine human immunity to the virus, which was previously only found in birds. The findings have implications for planning the public health response to this pandemic threat.

 

The study used a new, high throughput method that allows blood samples to be analysed for antibodies to multiple human and animal influenza viruses at the same time and is easier to standardise than previous techniques. However, the assay is yet to be validated clinically for the H7N9 virus, and the researchers caution that the results must be interpreted with care.

 

<SNIP>

The results reveal that although the level of antibodies to the H7 sub-type of flu virus are higher than any of the H5 sub-types tested, levels of antibodies to all five bird flu viruses are much lower than to human flu viruses. This suggests that people living in this particular area of Vietnam have had very little or no exposure to the H7 sub-type of virus, similar to other bird flu viruses. As this population of people would be expected to be among the first to be affected in the event of a pandemic, these findings have important implications for pandemic preparedness plans in this area.

<SNIP>

Professor Marion Koopmans, who is Head of Virology at the RIVM and senior author of the study, said: "We developed this technique exactly to be used in the current situation: we wanted a standardised test that allowed us to rapidly compare antibodies to the new virus with those to influenza viruses that we already know are common in people. The level of immunity to a new virus is one of the important questions during any emerging disease outbreak. We need only one drop of blood, so that tests can also be run when only small sample volumes are available, for instance when testing children. For outbreak investigations, testing of animals may be needed, and we are currently working on that. To do the clinical validation studies, we need blood samples from patients (and animals) with confirmed H7N9, and we hope to be able to do that soon through collaborations with other groups working on H7N9."

 

(Continue . . . )

Thursday, January 24, 2013

Two Studies On The 2009 Pandemic Flu Vaccine & Pregnancy

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Photo Credit – CDC

 

 

# 6877

 

We’ve known for a long time that influenza and pregnancy are a bad combination - one that can endanger both the mother and unborn child’s life – and that women are more susceptible to influenza when they are pregnant.

 

During the 1918 pandemic an abnormally high number of pregnant women died from the influenza, and those that survived endured a very high miscarriage rate.  Again, during the much milder 1957 Asian Flu, pregnant women reportedly suffered disproportionately higher mortality rates than non-pregnant women of the same age.

 

Historical reviews of both events are available in a Perspective, written by 3 CDC physicians (Sonja A. Rasmussen,  Denise J. Jamieson, Joseph S. Bresee) and published in the CDC Journal of EID article, Pandemic Influenza and Pregnant Women in February of 2008.

 

True to form, the 2009 H1N1 pandemic saw similarly high rates of influenza complications among pregnant women. 

 

An open access research article in the BMJ in 2011 (Perinatal outcomes after maternal 2009/H1N1 infection: national cohort study) found that pregnant women who were admitted to the hospital with an  H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.

 

Over the past decade we’ve also seen a handful of studies tentatively linking prenatal exposure to influenza (or an influenza-like-illness) with a variety of child and adolescent development disorders (see Of Pregnancy, Flu & Autism).

 

All of which explains why the CDC, the WHO, and other public health stress the importance of seasonal flu vaccination for pregnant women.

 

Despite all of this evidence of harm from influenza - there remains some reluctance among pregnant women to get the shot - in part due to the persistent anti-vaccine rhetoric on the internet and in the media.

 

Despite studies showing exactly the opposite effect, during and after the 2009 H1N1 pandemic there were unfounded claims that the 2009 H1N1 vaccine was responsible for `thousands’ of miscarriages.

 

Our first stop then is a study that recently appeared in the NEJM that looked at a large cohort of pregnant Norwegian women during the pandemic, and found that while influenza increased the rate of fetal deaths, that vaccination did not, and may have reduced the number fetal deaths.

 

Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination

Siri E. Håberg, M.D., Ph.D., Lill Trogstad, M.D., Ph.D., Nina Gunnes, Ph.D., Allen J. Wilcox, M.D., Ph.D., Håkon K. Gjessing, Ph.D., Sven Ove Samuelsen, Ph.D., Anders Skrondal, Ph.D., Inger Cappelen, Ph.D., Anders Engeland, Ph.D., Preben Aavitsland, M.D., Steinar Madsen, M.D., Ingebjørg Buajordet, Ph.D., Kari Furu, Ph.D., Per Nafstad, M.D., Ph.D., Stein Emil Vollset, M.D., Dr.P.H., Berit Feiring, M.Sc.Pharm., Hanne Nøkleby, M.D., Per Magnus, M.D., Ph.D., and Camilla Stoltenberg, M.D., Ph.D.

N Engl J Med 2013; 368:333-340J anuary 24, 2013 DOI: 10.1056/NEJMoa1207210

Conclusions

Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis.

 

Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.)

 

This was not the first study to show the safety of the 2009 pandemic flu vaccination in pregnancy, only the latest. 

 

Last year, in BMJ: H1N1 Vaccination & Fetal Death Rates, we looked at a study on a large cohort of pregnant women from Demark that reassuringly found no increase in miscarriage among those who received the 2009 H1N1 vaccine.

 

We saw similar results in 2010 (see Hong Kong: No Increase In Fetal Death Among Vaccine Recipients).  For more studies on the safety of flu vaccines in pregnancy, see IDSA: Flu Vaccines In Pregnancy.

 


Our second study, published overnight in PLoS One, looks at transplacental transfer of antibodies following vaccination with the AS03A-Adjuvanted H1N1 2009 Vaccine.

 

As infants are highly susceptible to influenza, and vaccination is not recommended before the age of 6 months, the receipt of vaccine derived antibodies from the mother while still in the womb might provide needed protection.

 

This study looked for antibodies in cord blood samples taken from babies shortly after delivery from 77 vaccinated and 27 unvaccinated women during the fall and winter of 2009.

 

Multi-Centre Observational Study of Transplacental Transmission of Influenza Antibodies following Vaccination with AS03A-Adjuvanted H1N1 2009 Vaccine

Richard Puleston , George Bugg, Katja Hoschler, Justin Konje, James Thornton, Iain Stephenson, Puja Myles, Joanne Enstone, Glenda Augustine, Yvette Davis, Maria Zambon, Karl Nicholson, Jonathan Nguyen-Van-Tam

Abstract

Introduction

Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009–10 pandemic.

Methods

In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres.

Results

Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2–84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3–38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2–87.1), maintained in most cases for at least 16 weeks.

Discussion

Immunization of pregnant women with AS03A-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.

 

In the body of the study, the authors caution:

Although there are no established correlates of protection for HI or MN in children and infants, evidence is accumulating that antibodies against seasonal influenza viruses, at levels that are normally associated with protection, can be found in a high proportion of cord blood samples  and neonates following immunization during pregnancy.

 

Our study found that three-quarters of vaccinated women had ‘seroprotective’ cord blood HI antibody titres of ≥1:40 that are associated with at least 50% protection against symptomatic influenza in adults.

 

Once again, this is not the first study to show a potential `protective effect’ to the fetus from maternal flu vaccination. In 2011, in saw:

 

Impact of maternal immunization on influenza hospitalizations in infants

American Journal of Obstetrics and Gynecology, 2011; 204 (6): S141 DOI:

Katherine A. Poehling, Peter G. Szilagyi, Mary A. Staat, Beverly M. Snively, Daniel C. Payne, Carolyn B. Bridges, Susan Y. Chu, Laney S. Light, Mila M. Prill, Lyn Finelli, Marie R. Griffin, Kathryn M. Edwards.

 

This study analyzed data collected by CDC and the New Vaccine Surveillance Network between 2002 and 2009 (before the H1N1 pandemic), and found that infants born to mothers who had received the flu vaccine during pregnancy were more than 45% less likely to be hospitalized with laboratory confirmed influenza.

 

In October of 2010, in Study: Protecting Two With One Shot I blogged on Lisa Schnirring’s CIDRAP News story regarding a study that showed that babies born to mothers who received the flu vaccination experienced fewer infections and hospitalizations during their first six months than babies whose mothers did not.

 

And two years before that, we saw a study conducted in Bangladesh (see CIDRAP’s Study: Flu shots in pregnant women benefit newborns) that offered pretty much the same conclusion.

 

While we may wish that flu shots were more effective in preventing illness (see CIDRAP: The Need For `Game Changing’ Flu Vaccines), flu shots are still considered the best preventative action you can take against influenza, and serious side effects are extremely rare.

 

And for pregnant women and their unborn child, the evidence continues to show that the real risks come from influenza virus, not from the vaccine.

Wednesday, January 16, 2013

EID Journal: Ebola Virus Antibodies From Bats In Bangladesh

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Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

# 6861

 

 

Several months ago in a blog called Virology Journal: Ebola Virus In Chinese Bats, we looked at the first evidence suggesting that Ebola viruses are circulating among bats in China, although the exact strain involved wasn’t clear.

 

Researchers were able to detect cross-reactive antibodies to two types of Ebola viruses (Zaire and Reston), but identification of the exact EBOV strain in China was not possible.

 

The natural reservoir for Ebola viruses are believed to be fruit bats of the Pteropodidae family, although the virus in humans is usually linked to the consumption of infected bushmeat (considered an intermediate host).

 

There are currently five known strains of the Ebola virus - Ebola-Zaire, Ebola-Sudan, Ebola-Reston, Ebola-Ivory Coast and Ebola-Bundibugyo – which along with a close cousin - the Marburg virus - make up the family Filoviridae.

 

Of these, only Ebola-Reston – found primarily in the Philippines – does not cause illness in humans.

 

Up until recently, Ebola Reston was the only ebolavirus thought to circulate outside of Africa.

 

Today, the CDC’s EID JOURNAL published a Dispatch that describes the seroprevalence of cross reactive antibodies against Ebola in bats tested in Bangladesh. A few excerpts, but follow the link to read the dispatch in its entirety.

 

Volume 19, Number 2—February 2013
Dispatch

Ebola Virus Antibodies in Fruit Bats, Bangladesh

Kevin J. Olival , Ariful Islam, Meng Yu, Simon J. Anthony, Jonathan H. Epstein, Shahneaz Ali Khan, Salah Uddin Khan, Gary Crameri, Lin-Fa Wang, W. Ian Lipkin, Stephen P. Luby, and Peter Daszak

Abstract

To determine geographic range for Ebola virus, we tested 276 bats in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; no virus was detected by PCR. These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses to mainland Asia.

<SNIP>

Conclusions

Our study provides evidence of Ebola virus infection in wildlife from mainland Asia and corroborates the observation that filoviruses are harbored across a much larger geographic range then assumed (2). Preferential reactivity to ZEBOV suggests exposure to an Ebola virus that is distinct from REBOV, the only filovirus currently found in Asia. We consider the likelihood of cross-reactivity with MARV as low because there is only a 35% aa identity between nucleoprotein genes of REBOV/ZEBOV and MARV. However, we cannot rule out co-infection with multiple filoviruses.

(Continue . . . )

 

An interesting side note, one of the authors listed on this dispatch is Professor Ian Lipkin, director of Columbia University’s Center for Infection and Immunity in New York. 

 

Dr. Lipkin served as technical advisor for the  2011 film Contagion, and created the fictional MEV-1 bat virus used as the movie’s viral villain  (see The Scientific Plausibility of `Contagion’).

 

Our knowledge of the diseases carried by bats has expanded considerably since the early 1990s. Up until that time, the primary concern was rabies.  

 

During the 1990s – two new bat-borne viruses emerged - Nipah and Hendra - both henipaviruses of the family Paramyxoviridae.

 

The Hendra virus was first isolated in 1994 after the deaths of 13 horses and a trainer in Hendra, a suburb of Brisbane, Australia. A stable hand, who also cared for the horses, was hospitalized, but survived.

 

Over the past 18 years 40 outbreaks of Hendra virus – all involving horses – have been reported in Australia. Four human fatalities have been linked to the virus as well.

 

 

The debut of Nipah was in Malaysia in 1998, where the virus first jumped from bats to local swine herds, probably via bat droppings into the swine’s environment or food. From there, it jumped to humans, resulting in 265 cases of acute encephalitis and more than 100 deaths (cite).

 

This first human outbreak was initially thought to be due to Japanese encephalitis, and so precautions around pigs were delayed for nearly two months, allowing the virus to spread.

 

Over the past decade, Nipah has sparked a number of small outbreaks across Southern Asia, although the most intense activity has been centered around Bangladesh.

 

image

Nipah/Hendra Virus & Fruit Bat Home Range – WHO

 

The most notorious of the emerging bat-viruses has been  SARS-CoV (coronavirus), which sparked an epidemic in 2002-2003 that infected roughly 8,000 people around the globe, killing nearly 800.

 

Which explains why so much interest has been paid to the detection last year of a handful of novel coronavirus infections in the Middle East (see WHO Coronavirus Update).

 


And perhaps most surprisingly of all, early in 2012 we learned about a new strain of influenza found in an unusual host: bats (see A New Flu Comes Up To Bat).

 

This discovery adds an H17 flu subtype, and a new host species, suddenly making all of the textbooks and slide presentations on influenza out of date.

 

In 2007 a PNAS article called A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans, told of a 39 year old man infected when a bat flew into their Malaysian home.  More than a week after he was placed in isolation, two other members of his family came down with the same illness, suggesting H-2-H transmission. 

 

The authors of that report wrote:

 

Bats, probably the most abundant, diverse, and geographically dispersed vertebrates on earth, have recently been shown to be the reservoir hosts of a variety of zoonotic viruses responsible for severe human disease outbreaks, some with very high mortality.

 

While most researchers expect the next pandemic to come from a swine or avian source, other species – like bats – are increasingly being looked to as significant reservoirs of dangerous zoonotic pathogens.

 

All of which makes studies, like this one today, of particular interested to researchers.

Thursday, August 23, 2012

NEJM: Adult-Onset Immunodeficiency in Thailand and Taiwan

image

M. fortuitum a “rapidly-growing” Mycobacterium Credit CDC PHIL

 

# 6511

 

 

Investigators at the NIH have identified an antibody suspected to be the cause of a noninfectious AIDS-like syndrome observed in Asia in recent years, one that can make people susceptible to opportunistic infections like those from nontuberculous mycobacteria (NTM).

 

Mycobacteria are slender, rod-shaped bacteria commonly found in the environment throughout the world.

 

Generally divided into three groups, the most famous are the bacilli that cause cause Tuberculosis and Leprosy (Hansen’s Disease) – while the third group - responsible for NTMs - are less well known.

 

Nontuberculous mycobacterial (NTMs) infections are rarely seen among non-HIV positive (or otherwise pulmonary or immune compromised) patients, but has been observed with increasing frequency over the past decade, particularly in Asia.

 

A couple of cites from the last decade include:

J Infect. 2006;53:77–84

Emergence of disseminated infections due to nontuberculous mycobacteria in non-HIV-infected patients, including immunocompetent and immunocompromised patients in a university hospital in Taiwan.

Lai CC, Lee LN, Ding LW, Yu CJ, Hsueh PR, Yang PC.

 

Clin Infect Dis. 2007 Aug 15;45(4):421-7. Epub 2007 Jul 5.

Disseminated nontuberculous mycobacterial infection in patients who are not infected with HIV in Thailand

Chetchotisakd P, Kiertiburanakul S, Mootsikapun P, Assanasen S, Chaiwarith R, Anunnatsiri S

 

 


While some sort of immune compromising condition has been associated with these opportunistic infections, until now the mechanism behind them has been a mystery. 

 

Today, an NIH study appearing in the NEJM finds that high-titers of anti–interferon-γ autoantibodies (i.e. an antibody directed against the body’s own immune system) are associated with opportunistic infections -like NTM - in non-HIV positive patients.

 

Interferon-y (IFN-γ) – or type II interferon - is a cytokine that is a critical component of our body’s innate and adaptive immune system. Antibodies that inhibit or neutralize their function would be expected to greatly assist opportunistic infections in spreading.

 

First a link to the study, then more details from the NIH press release.

 

 

Adult-Onset Immunodeficiency in Thailand and Taiwan

 

Sarah K. Browne, M.D., Peter D. Burbelo, Ph.D., Ploenchan Chetchotisakd, M.D., Yupin Suputtamongkol, M.D., Sasisopin Kiertiburanakul, M.D., Pamela A. Shaw, Ph.D., Jennifer L. Kirk, B.A., Kamonwan Jutivorakool, M.D., Rifat Zaman, B.S., Li Ding, M.D., Amy P. Hsu, B.A., Smita Y. Patel, M.D., Kenneth N. Olivier, M.D., Viraphong Lulitanond, Ph.D., Piroon Mootsikapun, M.D., Siriluck Anunnatsiri, M.D., Nasikarn Angkasekwinai, M.D., Boonmee Sathapatayavongs, M.D., Po-Ren Hsueh, M.D., Chi-Chang Shieh, M.D., Ph.D., Margaret R. Brown, B.S., Wanna Thongnoppakhun, Ph.D., Reginald Claypool, R.N., Elizabeth P. Sampaio, M.D., Ph.D., Charin Thepthai, M.Sc., Duangdao Waywa, M.Sc., Camilla Dacombe, R.N., Yona Reizes, R.N., Adrian M. Zelazny, Ph.D., Paul Saleeb, M.D., Lindsey B. Rosen, B.S., Allen Mo, B.S., Michael Iadarola, Ph.D., and Steven M. Holland, M.D.

N Engl J Med 2012; 367:725-734 August 23, 2012

Conclusions

Neutralizing anti–interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection.

 

And more details from NIH/NIAID.

 

NIH Researchers Find Possible Cause Of Immune Deficiency Cases In Asia

Autoantibody May Cause Susceptibility to Opportunistic Infections

WHAT:


A clinical study led by National Institutes of Health investigators has identified an antibody that compromises the immune systems of HIV-negative people, making them susceptible to infections with opportunistic microbes such as nontuberculous mycobacteria (NTM). In this study conducted at hospitals in Thailand and Taiwan, the researchers found that the majority of study participants with opportunistic infections made an antibody against interferon-gamma (IFN-gamma), a cell-signaling molecule thought to play a major role in clearing harmful infections. The study findings will appear online in the August 23rd issue of the New England Journal of Medicine.

 

NTM are close relatives of the bacterium that causes tuberculosis and can cause severe lung disease. NTM and other opportunistic infections are common in people with immune deficiency diseases, such as AIDS, but they are rare in people with healthy immune systems. However, researchers in Southeast Asia have recently reported several cases of NTM infections in people with no known problems with their immune systems.

 

The study, led by Sarah Browne, M.D., of the National Institute of Allergy and Infectious Diseases, and Peter Burbelo, Ph.D., of the National Institute of Dental and Craniofacial Research, enrolled 203 people, ages 18 to 78 years old. Of these participants, 52 had NTM infections, 45 had other opportunistic infections with or without NTM co-infection, 58 had tuberculosis, and 48 were healthy volunteers. All participants were HIV-negative.
The investigators examined participant blood samples for antibodies to cell-signaling molecules such as IFN-gamma. Eighty-eight percent of the people with NTM or other opportunistic infections had antibodies that blocked their own IFN-gamma (called autoantibodies).

 

The autoantibodies inhibited IFN-gamma function, hindering the immune system’s ability to clear infection, causing a syndrome that made these study participants more vulnerable to opportunistic infections. More work is needed to determine why people in Southeast Asia appear to be predisposed to the development of this autoimmune condition.

Because the average age of the study participants with NTM or other opportunistic infections was 50 years, the investigators speculate that these antibodies develop over time as a result of combined genetic and environmental factors. Having identified the likely cause of this syndrome, the study authors say it may be possible to treat the underlying problem by targeting the cells that make the IFN-gamma autoantibodies.

ARTICLE:
SK Browne et al. Adult onset immunodeficiency in Thailand and Taiwan. New England Journal of Medicine. DOI: 10.1056/NEJMoa1111160 (2012).