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NIH Study: Candidate H7N9 Avian Flu Vaccine Works Better With Adjuvant
An experimental vaccine designed to protect people against H7N9 avian influenza prompted immune responses in 59% 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 II study enrolled 700 healthy adults 19 to 64 years of age at four NIAID-sponsored vaccine and treatment evaluation units in the U.S. The results were published in JAMA.
The first recognized human H7N9 avian influenza cases occurred in China in early 2013. Most of the people who became 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% 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, MD. “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. The adjuvant, MF59, is used widely in Europe but is not licensed in the U.S.
In the study, 700 study volunteers were divided into groups of approximately 100 each. All of the participants 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 the vaccine at doses of either 15 mcg or 45 mcg without adjuvant.
Without adjuvant, even those participants who received the higher dose of vaccine showed minimal immune responses. This was not unexpected, as an earlier clinical trial of an experimental non-adjuvanted vaccine based on the H7 avian influenza virus elicited little or no detectable antibody responses.
The remaining five groups of participants received two injections of the vaccine at one of three different doses (3.75 mcg, 7.5 mcg, or 15.0 mcg). Three of the groups received the MF59 adjuvant with both inoculations, whereas the final two groups received only one dose of adjuvant with their first or second vaccine injection.
No serious vaccine-related adverse events were reported in any of the treatment groups. Subjects who received adjuvant reported more mild pain and tenderness at the inoculation site than did those who received only vaccine. In general, the inoculations were well-tolerated, and side effects were mild.
The researchers used a standard 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 has 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% had HAI levels of 40 or more.
The most surprising finding, noted the researchers, came from the group that received 15-mcg doses of vaccine and just one dose of MF59 at the time of the first vaccine. In that group, the antibody responses were not significantly lower than those in subjects 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 particularly important 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.
Source: NIH; October 7, 2014.