CDC: Sierra Leone Ebola Vaccine Trial Begins

 

 

# 9938

 

Yesterday the NIH published a summary of a early-stage clinical trial of an investigational Ebola vaccine called VSV-ZEBOV, and reported that it appeared safe  and produced robust antibody responses in all 40 of the healthy adults who received it (see April 13, 2015 Ebola Vaccine Candidate Promising in Early Study).

 

This summary described the results:

Most volunteers who received the vaccine developed antibodies against the Zaire species of Ebola virus within 14 days of injection. All developed this sign of an immune system response by 28 days after vaccine injection. The immune response was substantially higher in those who received the higher vaccine dose.

The volunteers tolerated the vaccine well. The most common side effects were injection site pain and transient fever that appeared and resolved within 12 to 36 hours after vaccination. The volunteers were asked about new arthritis symptoms, since some volunteers in another study of this candidate vaccine reported arthritis symptoms starting in the second week after vaccination. No episodes were reported by any of the volunteers in the NIH-WRAIR study.

“The prompt, dose-dependent production of high levels of antibodies following a single injection and the overall favorable safety profile of this vaccine make VSV-ZEBOV a promising candidate that might be particularly useful in outbreak interventions,” Davey says.

 

Today the CDC has announced that a large scale trial of this experimental vaccine is to begin in Sierra Leone, where 6,000 healthcare workers will receive the experimental vaccine.

 

Ebola vaccine trial begins in Sierra Leone

6,000 health and other frontline workers will receive vaccine in five districts of the country 

Press Release

For Immediate Release: Tuesday, April 14, 2015

 The Centers for Disease Control and Prevention (CDC), in partnership with the Sierra Leone College of Medicine and Allied Health Sciences (COMAHS) and the Sierra Leone Ministry of Health and Sanitation (MoHS), is now enrolling and vaccinating volunteers for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). This study will assess the safety and efficacy of the rVSV-ZEBOV candidate Ebola vaccine among health and other frontline workers.

“A safe and effective vaccine would be a very important tool to stop Ebola in the future, and the frontline workers who are volunteering to participate are making a decision that could benefit health care professionals and communities wherever Ebola is a risk,” said CDC Director Tom Frieden, M.D., M.P.H.  “We hope this vaccine will be proven effective but in the meantime we must continue doing everything necessary to stop this epidemic —find every case, isolate and treat, safely and respectfully bury the dead, and find every single contact.”

STRIVE will enroll about 6,000 health and other frontline workers. It will be conducted in Western Area Urban district, which includes Freetown, Western Area Rural district, and certain chiefdoms in Bombali, Port Loko, and Tonkolili districts. These study locations were selected because they have been heavily affected by the Ebola outbreak in the past few months.

“We are happy to be partnering with MoHS and CDC on this important study, which may help to prevent future cases of Ebola,” said Mohamed Samai, M.B., Ch.B., Ph.D., acting Provost of COMAHS and the study’s principal investigator. “It brings me hope and pride that my country can take from this devastating epidemic something that may benefit people around the world.”

When participants enroll in the study, they will be assigned randomly to one of two timeframes for vaccination – either immediately or about six months later. All study participants will receive the vaccine and be followed closely for six months. The study will evaluate if and how well the vaccine worked by comparing rates of Ebola virus disease in those who are vaccinated to those who have not yet received the vaccine.

The rVSV-ZEBOV candidate vaccine uses a vesicular stomatitis virus carrying a non-infectious Ebola virus gene. The vaccine cannot cause Ebola virus disease but can potentially stimulate an immune response to protect against the disease. The vaccine was developed by the Public Health Agency of Canada’s National Microbiology Laboratory and licensed to NewLink Genetics. In 2014, NewLink Genetics entered into a licensing and collaboration agreement with Merck to research, develop, manufacture, and distribute the rVSV-ZEBOV candidate vaccine. The vaccine has, and continues to be, studied in hundreds of people (as of March 26, 2015, more than 800 people) in Africa, Canada, Europe, and the United States. Results from early studies to date of the vaccine show an acceptable safety profile and indicate that the rVSV-ZEBOV candidate vaccine produces an immune response. The Biomedical Advanced Research and Development Authority is supporting the advanced development and manufacturing of the vaccine and is assisting CDC in conducting the clinical trial in Sierra Leone.

“We don’t know whether this vaccine will be the Ebola prevention tool we’re all eager for, but we hope that what we learn from STRIVE will help us save lives during this and future Ebola outbreaks,” said Anne Schuchat, M.D., Director of CDC’s National Center for Immunization and Respiratory Diseases.

Because it is not yet clear how much protection, if any, the rVSV-ZEBOV candidate vaccine may offer, health and other frontline workers who receive the vaccine should continue to take full preventive actions to protect themselves from Ebola, including proper training, focused protocols and procedures, and use of all recommended personal protective equipment.

NIH Statement On Early Ebola Vaccine Trial Data

A 39-year-old woman receives a dose of the investigational NIAID/GSK Ebola vaccine at the NIH Clinical Center in Bethesda, Maryland.

 

# 9443

 

Although previously reported in a NEJM article (see Chimpanzee Adenovirus Vector Ebola Vaccine — Preliminary Report), the NIH has produced the following statement regarding the early, encouraging  results of phase I testing of an Ebolavirus vaccine.

 

Note: This NIAID/GSK candidate vaccine is not the same vaccine whose trial was temporarily halted last week after four test subjects developed joint pains (see Ebola Vaccine Trial Halted Temporarily After Joint Pains: Geneva Hospital).

 

While there is still a long way to go before this – or any other Ebola vaccine – can be certified as both safe and effective, these early results will help pave the way for Phase 2/3 clinical trials, likely to be held in West Africa.

 

 

Ebola Vaccine Prompts Immune Response

December 15, 2014

At a Glance

• An experimental vaccine to prevent Ebola virus disease was well-tolerated and produced immune system responses in all 20 healthy adults who received it.
• Based on these results, researchers are planning further trials to assess the safety and effectiveness of the vaccine.

The Ebola virus spreads through direct contact with the blood or secretions of an infected person. The 2014 Ebola outbreak in West Africa is the largest Ebola outbreak in history. As of early December, more than 17,000 cases and 6,000 deaths have been reported. There are no approved drugs, but early care can improve survival. The scale of this outbreak has intensified efforts to develop a protective vaccine.

NIH’s National Institute of Allergy and Infectious Diseases (NIAID) developed and tested 3 earlier investigational Ebola vaccine candidates that began Phase 1 clinical trials in 2003. The candidate Ebola vaccine in the current study was developed collaboratively by scientists at NIAID’s Vaccine Research Center and GlaxoSmithKline (GSK) based on knowledge gained from those earlier studies.

The NIAID/GSK candidate vaccine contains segments of genetic material from 2 Ebola virus species, known as Sudan and Zaire. The genetic material is delivered by a carrier virus, or vector, called chimpanzee-derived adenovirus 3, which causes a common cold in chimpanzees but no illness in humans. Both the vector and the Ebola genetic material have been shown to be safe in humans in other studies.

Twenty volunteers between the ages of 18 and 50 participated in the phase 1 clinical trial, which took place at the NIH Clinical Center. Ten received an intramuscular injection of vaccine at a lower dose and 10 at a higher dose. The team reported their interim results online on November 26, 2014, in the New England Journal of Medicine.

All 20 volunteers produced anti-Ebola antibodies within 4 weeks of receiving the vaccine. Antibody levels were higher in those who received the higher dose vaccine. The vaccine also prompted the production of immune system cells called CD8 T cells, which are important to immune protection. Four weeks after vaccination, CD8 T cells were detected in 2 volunteers who had received the lower dose and 7 who had received the higher dose vaccine.

“We know from previous studies in nonhuman primates that CD8 T cells played a crucial role in protecting animals that had been vaccinated with this NIAID/GSK vaccine and then exposed to otherwise lethal amounts of Ebola virus,” says first author Dr. Julie E. Ledgerwood. “The size and quality of the CD8 T cell response we saw in this trial are similar to that observed in nonhuman primates vaccinated with the candidate vaccine.”

No serious adverse effects were seen in any of the volunteers. Two people who received the higher dose vaccine developed a brief fever within a day of vaccination.

This and other Ebola vaccine candidates continue to be evaluated by international research teams.

Related Links:

• Questions and Answers, Phase 1 Clinical Trials of NIAID/GSK Investigational Ebola Vaccine:
  http://www.niaid.nih.gov/news/QA/Pages/EbolaVaxResultsQA.aspx
• NIH Accelerates Clinical Trials of Ebola Vaccines:
  http://www.fic.nih.gov/News/GlobalHealthMatters/november-december-2014/Pages/ebola-nih-vaccine-clinical-trials.aspx
• Computer Models Can Help Guide Ebola Response:
  www.nih.gov/researchmatters/november2014/11102014ebola.htm
• Genetics of the 2014 Ebola Outbreak:
  http://www.nih.gov/researchmatters/september2014/09152014ebola.htm
• Ebola/Marburg:
  http://www.niaid.nih.gov/topics/ebolaMarburg
• Ebola Virus Disease: Information for U.S. Healthcare Workers:
  http://www.nih.gov/health/ebola.htm

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NIH: H7N9 Vaccine Candidate Works Much Better With An Adjuvant

 

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Although it is difficult to get anyone to care about anything other than Ebola right now, the truth is there are a number of other emerging viruses that also have a high fatality rate, and that carry with them a reasonable degree of pandemic potential.  

 

H5N1 – which emerged in Vietnam in 2003 and subsequently spread across much of Asia and into the Middle East – is perhaps the best known avian flu virus, but H7N9 – which first appeared in the spring of 2013- is seen as being an even bigger threat (see Eurosurveillance: Genetic Tuning Of Avian H7N9 During Interspecies Transmission).

 

Producing an effective human vaccine against H7N9 has been viewed as presenting serious challenges, as previous experimental  H5 and H7 vaccines have required unusually large amounts of antigen (up to 12x normal) to induce a good immune response.

 

A specification that would greatly reduce the number of shots that could be produced each year, and would cripple any emergency vaccination response. 

 

One possible solution is the use of adjuvants   - additives often used in European flu vaccines to increase their immune response.  But adjuvants have never been licensed for use in U.S. flu vaccines, would likely require an EUA (Emergency Use Authorization), and might make some people reluctant to take the vaccine.

About a year ago, the we saw the NIH Begins Phase II Clinical Trials On H7N9 Vaccine Candidates, to test a variety of H7N9 vaccine formulations across two clinical trials - involving as many as 1700 volunteers - who would receive various strength H7N9 vaccines (adjuvanted and non-adjuvanted).

 

Today, the results of that trial have been published (​MJ Mulligan et al. Serological responses to an avian influenza A/H7N9 vaccine mixed at the point-of-use with MF59 adjuvant: a randomized clinical trial. JAMA)., and the following NIH press release provides us with the not unexpected news that the H7N9 candidate vaccine only produced an acceptable immune response when administered with an adjuvant. 

 

According to their study: Without adjuvant, immune responses produced by the investigational vaccine were minimal regardless of vaccine dosage.

 

Candidate H7N9 Avian Flu Vaccine Works Better with Adjuvant

Results of Large NIH-Sponsored Trial Published

​An experimental vaccine to protect people against H7N9 avian influenza prompted immune responses in 59 percent of volunteers who received two injections at the lowest dosage tested, but only if the vaccine was mixed with adjuvant—a substance that boosts the body’s response to vaccination. Without adjuvant, immune responses produced by the investigational vaccine were minimal regardless of vaccine dosage, according to findings from a clinical trial sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The Phase 2 trial enrolled 700 healthy adults aged 19 to 64 years old at four NIAID-sponsored Vaccine and Treatment Evaluation Units (VTEU) in the United States. It was led by Mark J. Mulligan, M.D., of Emory University, Atlanta. Results appear in the current issue of the Journal of the American Medical Association.

The first recognized human H7N9 avian influenza cases occurred in China in early 2013. Most people who have become infected with the virus had contact with infected poultry. The virus does not sicken birds, but can cause people to become seriously ill, with approximately 67 percent of reported cases requiring hospitalization. As of September 4, 2014, a total of 452 laboratory confirmed cases, including 166 deaths, had been reported to the World Health Organization.

“Although this influenza virus does not currently spread easily from person to person, all novel influenza viruses have the potential to evolve to cause widespread illness or death,” said NIAID Director Anthony S. Fauci, M.D. “Therefore, it is prudent to conduct clinical trials such as this one to be prepared in the event of an H7N9 avian influenza pandemic.”

The experimental vaccine, made from inactivated H7N9 virus grown in chicken eggs, was manufactured by Sanofi Pasteur (Swiftwater, PA). The adjuvant, MF59, used widely in Europe but not licensed in the United States, was manufactured by Novartis Vaccines (Marburg, Germany) and was mixed with the vaccine just prior to use. Both products were supplied by the Biomedical Advanced Research and Development Authority (a part of the Department of Health and Human Services) from the National Pre-Pandemic Influenza Vaccine Stockpile.

The 700 study volunteers were divided into groups of approximately 100 each. All received two injections, spaced 21 days apart, and had blood drawn on both inoculation days as well as on three additional time points. Two groups received vaccine at either 15 micrograms (mcg) or 45 mcg without adjuvant. Without adjuvant, even those participants who received the higher dosage vaccine had minimal immune responses. This was not unexpected, as an earlier clinical trial of an experimental unadjuvanted vaccine based on H7 avian influenza virus elicited little or no detectable antibody responses.

The remaining five groups of participants received two injections of vaccine at one of three different dosages (3.75 mcg, 7.5 mcg or 15 mcg). Three of the groups received MF59 adjuvant with both inoculations, while the final two groups received only one dose of adjuvant with their first or second injection of vaccine. No serious vaccine-related adverse events were reported in any of the groups. Participants who received adjuvant reported more mild pain and tenderness at the inoculation site than those who received only vaccine. In general, the inoculations were well-tolerated and side effects were mild.

The researchers used a standard test called the hemagglutination inhibition (HAI) antibody assay to assess the likelihood that the experimental vaccine would provide protection against influenza disease. HAI levels of 40 or more signal that an influenza vaccine induced an immune reaction that is likely to prevent influenza disease. In this trial, the key HAI assays were performed on blood samples taken at 42 days after the first inoculation.

Among the volunteers who received two injections of the lowest dose of vaccine along with two doses of adjuvant, 59 percent had HAI levels of 40 or more. The most surprising finding, noted the researchers, came from the volunteer group that received 15 mcg dose vaccines and just one dose of MF59 at the time of the first vaccine. Among that group, the antibody responses were not significantly lower than those who received two doses of adjuvant, suggesting that a single dose of adjuvant given with the first dose of vaccine may be sufficient to prompt a significant immune response. If true, this would be of particular importance in the event of a pandemic, when adjuvant-sparing and vaccine antigen-sparing vaccine regimens could be used to stretch available supplies of vaccine and adjuvant as far as possible.

In addition to Emory University, the NIAID VTEUs at Cincinnati Children’s Hospital and Medical Center; the University of Iowa in Iowa City; and the University of Texas Medical Branch at Galveston participated in this trial.

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NIH Begins Phase II Clinical Trials On H7N9 Vaccine Candidates

 

 

# 7785

 

As we’ve discussed before, the production of an H7N9 vaccine is not going to be as simple, or straightforward, as was the H1N1 pandemic vaccine in 2009.   With that flu - it was essentially a strain change - substituting the swine-origin H1N1 virus for the seasonal H1N1 component that has been part of the flu shot for decades.

 

Avian viruses – like H5 and H7 – are an entirely different kettle of fish, and prior experiences with H5N1 and H7N1 vaccines has shown that they are not so easily made.

 

Last May we saw an analysis of some of the problems inherent in creating and deploying an  H7N9 vaccine published in JAMA, penned by CIDRAP’s  Michael T. Osterholm, PhD, MPH; Katie S. Ballering, PhD; and Nicholas S. Kelley, PhD.

Major Challenges in Providing an Effective and Timely Pandemic Vaccine for Influenza A(H7N9)

Michael T. Osterholm, PhD, MPH; Katie S. Ballering, PhD; Nicholas S. Kelley, PhD

JAMA. 2013;():1-2. doi:10.1001/jama.2013.6589.

Published online May 9, 2013

 

Previous  H5 and H7 experimental vaccines have required unusually large amounts of antigen (up to 12x normal) to induce a good immune response, a specification that would greatly reduce the number of shots that could be produced each year.   One possible solution is the use of adjuvants   - additives often used in European flu vaccines to increase their immune response.

 

But adjuvants have never been used in the U.S. flu vaccines, would likely require an EUA (Emergency Use Authorization), and might make some people reluctant to take the vaccine.

 

Right now, no one knows what the optimal antigen/adjuvant formulation would be for an effective, and practical H7N9 vaccine.

 

Today, the NIH released a detailed summary of their plans to test a variety of H7N9 vaccine formulations across two clinical trials - involving as many as 1700 volunteers - who will received various strength H7N9 vaccines (adjuvanted and non-adjuvanted). When complete, we should have a much better idea of what will be involved in creating a pandemic H7N9 vaccine.  Full results, however,  are not expected until December of 2014.

 

National Institute of Allergy and Infectious Diseases (NIAID)

Contact

Jennifer Routh 
301-402-1663

For Immediate Release: Wednesday, September 18, 2013

NIH begins testing H7N9 avian influenza vaccine candidate

Possible role for adjuvants to be examined

Researchers at nine sites nationwide have begun testing in humans an investigational H7N9 avian influenza vaccine. The two concurrent Phase II clinical trials, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, are designed to gather critical information about the safety of the candidate vaccine and the immune system responses it induces when administered at different dosages and with or without adjuvants, substances designed to boost the body’s immune response to vaccination.

 

Human cases of H7N9 influenza first emerged in China in February 2013, with the majority of reported infections occurring in the spring. As of Aug. 12, 135 confirmed human cases, including 44 deaths, have been reported by the World Health Organization. Most of these cases involved people who came into contact with infected poultry. Although no H7N9 influenza cases have been reported outside of China and the virus has not demonstrated sustained person-to-person transmission, there is concern that it could mutate to pose a much greater public health threat.

 

“H7N9 avian influenza virus — like all novel influenza virus strains to which people have not been exposed — has the potential to cause widespread sickness and mortality,” said NIAID Director Anthony S. Fauci, M.D. “We are now testing a vaccine candidate with and without adjuvant in an effort to prepare for and, hopefully, protect against this possibility.”

 

The two clinical trials, which will enroll healthy adults ages 19 to 64, will evaluate an investigational H7N9 vaccine developed by Sanofi Pasteur. The candidate vaccine was made from inactivated H7N9 virus isolated in Shanghai, China in 2013. Adjuvants are being tested with the investigational vaccine because previous vaccine research involving other H7 influenza viruses has suggested that two doses of vaccine without adjuvant may not produce an immune response adequate to provide effective protection. In pandemic situations, adjuvants also can be used as part of a dose-sparing strategy, which would allow production of more doses of vaccine from the available supply of the viral antigen, thereby allowing a greater number of people to be vaccinated more quickly.

 

The first clinical trial, led by Mark J. Mulligan, M.D., of Emory University in Atlanta, will enroll as many as 700 study participants who will be randomly assigned to one of seven groups (up to 100 participants in each group). Each group will receive two equivalent dosages (3.75 micrograms [mcg], 7.5 mcg, 15 mcg or 45 mcg) of the candidate vaccine, approximately 21 days apart. Five of the groups will receive the vaccinations along with MF59 adjuvant, developed by Novartis Vaccines and Diagnostics.

 

Of these five groups, three will receive adjuvant with both vaccinations; one group of participants will receive adjuvant only with the first vaccination; and another group of participants will receive adjuvant only with the second vaccination. Two groups of participants will not receive adjuvant. The MF59 adjuvant that is being tested is also contained in the Fluad seasonal influenza vaccine currently licensed in Europe and Canada for use in people age 65 years or older.

 

The second trial, led by Lisa A. Jackson, M.D., M.P.H., of Group Health Research Institute in Seattle, will enroll as many as 1,000 participants. Each participant will be randomly assigned to one of 10 groups (up to 100 participants per group) and will receive two equivalent doses (same dosages as the other trial) of the investigational H7N9 vaccine given 21 days apart.

 

Seven of these groups will receive the vaccinations either with or without AS03 adjuvant, developed by GlaxoSmithKline Biologics. Two groups will receive their first vaccination with AS03 or MF59 adjuvant and then receive the alternate adjuvant at time of second vaccination. One group will receive the MF59 adjuvant at both vaccinations. The AS03 adjuvant that is being tested was used in a 2009 H1N1 influenza vaccine, Pandemrix, used in several European countries during the 2009-2010 H1N1 influenza pandemic.

 

In both studies, which are expected to conclude in December 2014, a panel of independent experts will closely monitor safety data at regular intervals throughout the trial.

 

The vaccine studies are being conducted at the eight NIAID-funded Vaccine and Treatment Evaluation Units: Baylor College of Medicine, Houston; Children’s Hospital Medical Center, Cincinnati; Emory University, Atlanta; Group Health Cooperative, Seattle; Saint Louis University, St. Louis; University of Iowa, Iowa City; University of Maryland School of Medicine, Baltimore; and Vanderbilt University, Nashville. The University of Texas Medical Branch at Galveston will conduct the trial as a subcontractor to Baylor College of Medicine.

 

Further information about both clinical trials can be found at http://www.ClinicalTrials.gov using the identifiers: NCT01938742 and NCT01942265.

For more information, visit NIAID’s Influenza Web portal. For U.S. government information on avian and pandemic influenza, see http://www.Flu.gov

 

NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

 

Regardless of what influenza virus causes the next pandemic, the reality is that it will take 5 or 6 months to begin to produce any useful quantity of vaccine, and many people would be waiting a year or more to receive one.

 

Instead – at least in the opening months -   we will be looking to measures like social distancing, school closures, hand hygiene & masks (aka Nonpharmaceutical Interventions NPIs) along with neuraminidase (NA) inhibiting antiviral drugs (NAIs) like oseltamivir (Tamiflu ®) and Zanamivir (Relenza ®) to help mitigate its impact.

 

 

Should H5N1, H7N9, MERS-CoV or any other novel virus threaten, we’ll be talking a good deal more about NPIs.

H5N1 Vaccine Research

BSL-3 – Credit CDC PHIL

 

# 6979

 

Seven years ago, when the H5N1 virus suddenly leapt out of a handful of southeast Asian countries to invade parts of Europe and the Middle East, pandemic concerns were understandably heightened.

 

As a result many countries hastened to create - or acquire - an emergency stockpile of experimental bird flu vaccine. 

 

 

In 2007, I wrote:

 

Switzerland has reportedly purchased 8 million doses of pre-pandemic vaccine, enough to inoculate their entire citizenry.  Denmark, it was widely reported last January, ordered in enough pre-pandemic vaccine for half of their population.  And in Australia, there has been talk of inoculating their entire nation.

 

New Zealand recently announced they had enough pre-pandemic vaccine on hand for 100,000 essential workers, and the UK is exploring the purchase of large quantities of vaccine.

While the WHO has never endorsed the idea, obviously there are a good many nations that view having a pre-pandemic vaccine as being a matter of national security.

 

Japan, Taiwan, the United States and others eventually acquired small to medium-sized quantities of H5N1 vaccine over the next couple of years.

 

With only a limited shelf life (usually around 3 years) - and based on an older clade of the virus - those early stockpiles have either already expired or will shortly.

 

While the feared bird flu pandemic has thus far failed to materialize, some countries have adopted a `use it or lose it’ strategy, offering the aging H5N1 jab to health care workers, veterinarians, and other high risk groups (see Hong Kong: H5N1 Vaccine Recommended For Certain Lab Workers).

 

Countries opting to `store’ their vaccine stockpile in the arms of healthcare and public safety workers have included Japan (see Japan Begins Pre-Pandemic Inoculation Of Health Care Workers) and Taiwan (see Taiwan Offers Public Bird Flu Vaccinations.)

 

Over the weekend, after the spate of H5N1 cases reported in Cambodia since the New Year, Taiwan once again announced plans to provide their H5N1 vaccine to certain high risk individuals.

 

Certain groups entitled to free avian flu vaccinations

2013/03/02 15:24:22

Taipei, March 2 (CNA) Taiwan has begun to provide free vaccinations against avian influenza H5N1 to people at high risk of contracting the deadly virus, such as laboratory staff, a senior health official said Saturday.

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Just as with the seasonal flu,  the H5N1 virus evolves into new clades, meaning that updated vaccines must be created and tested. The following chart from the World Health Organization shows just how much diversity the virus has acquired.

 

(click to load larger image)

 

While not garnering the sort of headlines that we saw in 2006-2007, researchers continue to work on creating and testing the next generation of bird flu vaccines.

 

Which brings us to a press release, sent to me by a reader, regarding a recent call (January, 2013) for volunteers to take part in an H5N1 vaccine clinical trial being conducted by the Wesley Research Institute in Queensland, Australia.

 

Wesley Research Institute conducts new bird flu vaccine study

 

Posted on January 14, 2013

The Wesley Research Institute Clinical Trials Centre is seeking volunteers aged 65 and over to participate in a new avian influenza (bird flu) vaccine study that may prevent the spread of infection and death.

 

H5N1 type influenza virus is a specific strain that resulted in rapid spread of influenza in birds and poultry (bird flu) across Asia, Europe and Africa. This strain has been associated with over 550 human cases (spread from animals) and about 320 deaths.

 

The number of Australians travelling overseas has grown at an unprecedented rate over recent years. 70% of Australians 60 years old and over, taking a holiday overseas in the last 12 months visited or at least stopped over at the Pacific Asia region where in 1997 the first outbreak of bird flu occurred.

 

The symptoms of bird flu are similar to those of other types of flu and the onset is sudden. The time from infection to the start of symptoms is usually three to five days, although in some cases it can be up to seven days. Symptoms usually last for up to a week. In many cases, bird flu can cause rapid deterioration, pneumonia (inflammation of the tissue of one or both lungs) and multiple organ failure, all of which can be fatal.

 

Travel safe, keep bird flu away!

You may be suitable to participate if:

• Generally healthy
• Aged 65 years old and over
• Able to attend visits at The Wesley Hospital in Auchenflower

Study volunteers will be compensated for their time and travel.

DOWNLOAD FLYER

 

 

While the H5N1 virus remains a major concern, there are other avian and swine influenza viruses that are being watched closely for signs of pandemic potential as well. Accordingly, the World Health Organization regularly updates their list of candidate flu strains for vaccine research and development.

 

Antigenic and genetic characteristics of A(H5N1), A(H7N3), A(H9N2) and variant influenza viruses and candidate vaccine viruses developed for potential use in human vaccines

February 2013

This summary provides a review on the A(H5N1), A(H7N3), A(H9N2) and variant influenza virus activity and virus characterization, and describes the current status of the development of candidate vaccine viruses for pandemic preparedness purposes. It is meant to provide guidance for national authorities and vaccine companies on the selection of candidate viruses for use in vaccine development.

GSK Pledges To Release All Drug Trial Data

 

# 6909

 

It’s genuinely big news this afternoon that GSK (Glaxo-Smith-Kline) has pledged that they will publish all results of clinical study reports (CSRs) and clinical trials, not only going forward, but also going back on all approved medications developed since the year 2000.

 

It is estimated that roughly half of all clinical trials never see the light of day, and in 2010 an NHS Health Technology Assessment concluded that:

 

Studies with significant or positive results were more likely to be published than those with non-significant or negative results . . .

 

I’ve written in the past on the reluctance of Roche to release all of their clinical trial data on Tamiflu, and in RCTs: All That’s Gold Standard Doesn’t Glitter, we looked at a Johns Hopkins Study on pediatric clinical trials that found:

 

Overall, 41 percent of the 146 trials in the review had improper or poorly described randomization techniques. Industry-funded trials were six times more likely to have high risk for biased randomization than government-funded trials or those funded by nonprofit organizations.

 

While public concerns over industry reporting bias and secrecy have grown over the years, the charge has really been led by All Trials Registered, All Results Reported.

 

An initiative of Sense About Science, Bad Science, BMJ, James Lind Initiative, the Centre for Evidence-based Medicine and others, their grassroots campaign has put considerable pressure on pharmaceutical companies to release their data.

 

Today, in what can only be described as a major victory for the AllTrials campaign, GSK posted the following announcement on their corporate website, pledging to publish detailed drug trial data.

 

GSK announces support for AllTrials campaign for clinical data transparency

Issued: Tuesday 5 February 2013, London UK

GSK today further demonstrated its commitment to clinical trial transparency by announcing its support for the AllTrials campaign. The campaign is calling for registration of clinical trials and the disclosure of clinical trial results and clinical study reports (CSRs) to help drive further scientific understanding.

 

GSK already publicly discloses a significant amount of information about its clinical trials. The company registers and posts summary information about each trial it begins and shares the results of all its clinical trials – whether positive or negative – on a website accessible to all. Today this website includes almost 5,000 clinical trial result summaries and receives an average of almost 11,000 visitors each month. The company has also previously committed to seek publication of the results of all of its clinical trials that evaluate its medicines to peer-reviewed scientific journals.

 

Expanding on this, GSK is committing to make CSRs publicly available through its clinical trials register. CSRs are formal study reports that provide more details on the design, methods and results of clinical trials and form the basis of submissions to the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and other regulatory agencies. From now, GSK will publish CSRs for all of its medicines once they have been approved or discontinued from development and the results have been published. This is to allow for the data to be first reviewed by regulators and the scientific community. Patient data in the CSRs and their appendices will be removed to ensure patient confidentiality is maintained.

 

In addition, while there are practical challenges, the company also intends to publish CSRs for clinical outcomes trials for all approved medicines dating back to the formation of GSK. This will require retrieval and examination of each historic CSR to remove confidential patient information. Given the significant volume of studies involved, the company will put in place a dedicated team to conduct this work which it expects to complete over a number of years. Posting will take place in a step-wise manner, with priority given to CSRs for its most commonly prescribed medicines.

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Hopefully this will be the first of many such industry announcements.

NIH: Any Combo Of Prime-Boost Flu Vaccine Protects Toddlers

 

 

# 5759

 

 

Children 6 months of age or older, who have never received a flu vaccine before, are recommended to receive a priming vaccine and a booster – one month apart – the first time.

 

For children over the age of 6 months, the TIV flu shot may be used, and for healthy children 24 months or older, the LAIV nasal spray may be substituted.

 

Until now, a lack of clinical studies have left some doubts as to whether a combination of the TIV flu shot and LAIV nasal vaccine would perform equally as well.

 

From the NIH today, we’ve a report on clinical trials conducted at Saint Louis University, along with investigators at Vanderbilt University in Nashville, and the Cincinnati Children's Hospital – funded by NIAID -that looks at the immune responses in toddlers who received one of four different flu shot combinations:

 

• two injections of a TIV vaccine
• two LAIV nasal spray vaccines
• A LAIV nasal spray followed by a TIV shot
• a TIV shot followed by the LAIV nasal spray

 

The good news . . . particularly for children at least 2 years of age with an aversion to needles . . . is that two sprays of the LAIV vaccine appear to produce the same level of antibody response as two flu shots.

 

And when a child receives at least one of their vaccines via the LAIV nasal spray, they produced a wider array of immune T cells, which may help protect against other flu strains.

 

This from NIH News.

 

 

Any Prime-Boost Mix of Injected or Spray Flu Vaccine Shields Toddlers

Broadest Immune Response from Nasal Spray Vaccine, NIH-Funded Study Finds

Children younger than 3 years old receive the same protective antibody response from the recommended two doses of licensed seasonal influenza vaccines regardless of whether the two doses are injected by needle, inhaled through a nasal spray or provided through one dose of each in any order, according to researchers funded by the National Institutes of Health. Doctors usually give young children two matching vaccines, and one goal of the study was to determine whether giving two different types of vaccines works just as well.

Daniel Hoft, M.D., Ph.D., conducted a trial of influenza vaccines in young children.
Credit: Saint Louis University

 

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The researchers found that all four dosing patterns were safe and induced similar levels of protective antibodies. However, when the investigators looked at responses from the T-cell arm of the immune system, a striking difference emerged. They could not detect influenza-specific T cells in children who received only TIV, according to Dr. Hoft. But, he added, “The kids who received at least one dose of LAIV nasal spray vaccine produced significant amounts of three important T-cell subtypes that are likely to confer additional protection beyond that afforded by antibodies alone.”

 

Previous studies have demonstrated that children are better protected against influenza infection and disease by LAIV than by TIV, Dr. Hoft noted. However, few studies have examined the T-cell responses elicited by LAIV when given to very young children who have little prior natural exposure to seasonal influenza viruses. Distinguishing T-cell responses due to vaccination from those arising after natural exposure to influenza virus becomes more difficult as a child ages, he explained. Because the children in the trial were all younger than 3 years old, the researchers could be confident that spikes in levels of the three T-cell subtypes they detected were likely due to the vaccinations.

 

Children who received only one dose of LAIV had T-cell responses similar to those who received two, and the order of vaccine types did not make a significant difference in the size of the T-cell response. However, because LAIV has sometimes been associated with increased incidence of wheezing in the youngest recipients, the results of this trial suggest that the best regimen for kids younger than 24 months may be TIV followed by LAIV, Dr. Hoft said. Larger clinical trials are required to confirm the safety and efficacy of such an approach, he added. 

 

(Continue . . . )

 

The results are published today in the Journal of Infectious Diseases, and the abstract may be read at:

 

Live and Inactivated Influenza Vaccines Induce Similar Humoral Responses, but Only Live Vaccines Induce Diverse T-Cell Responses in Young Children

Daniel F. Hoft, Elizabeth Babusis, Shewangizaw Worku, Charles T. Spencer, Kathleen Lottenbach, Steven M. Truscott, Getahun Abate, Isaac G. Sakala, Kathryn M. Edwards, C. Buddy Creech, Michael A. Gerber, David I. Bernstein, Frances Newman, Irene Graham, Edwin L. Anderson and Robert B. Belshe