NIH study also provides proof of concept for universal influenza vaccine
The immune response to an H5N1 avian influenza vaccine was greatly enhanced in healthy adults if they were first primed with a DNA vaccine expressing a gene for a key H5N1 protein, researchers say. Their report describes results from two clinical studies conducted by researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
A majority of study volunteers who received the DNA vaccine 24 weeks before receiving a booster vaccine made from whole, inactivated H5N1 virus produced high levels of antibodies thought to be protective against the globular head region of a protein called hemagglutinin (HA). Traditional seasonal influenza vaccines are designed to elicit antibodies to the head region of HA, but it changes each year and so vaccines must be repeated annually to maintain immunity. In some volunteers, the prime-boost vaccine regimen also spurred production of broadly neutralizing antibodies aimed at the HA stem, a region that is relatively constant across many strains of influenza viruses.
"The results of these studies demonstrate an important proof of concept, in that it is possible to elicit broadly neutralizing influenza antibodies in humans through vaccination," said NIAID Director Anthony S. Fauci, M.D. "These findings mark an early but significant milestone on the pathway to a universal influenza vaccine that provides protection against multiple virus strains."
The findings from the Phase I clinical trials appear in an article online Oct. 4 in The Lancet Infectious Diseases. Gary J. Nabel, M.D., Ph.D., director of the NIAID Vaccine Research Center (VRC), and his colleagues developed the H5N1 influenza DNA vaccine. The other vaccine used in the study was made by Sanofi Pasteur, located in Swiftwater, Pa.
In 2010, VRC studies in mice, ferrets and monkeys showed that a DNA prime-boost influenza vaccine regimen can elicit broadly neutralizing antibodies directed against the HA stem. "Now we see that it is possible to elicit HA stem-directed antibodies in people as well," said Dr. Nabel. The VRC researchers are hoping to apply this approach to research on vaccines against other seasonal and pandemic influenza strains too.
Since 2003, there have been 564 confirmed cases of human H5N1 influenza infection and 330 associated deaths worldwide, according to the most recent figures from the World Health Organization. Developing an effective vaccine against H5N1 influenza has proved difficult, because vaccines containing the whole, inactivated virus often fail to generate high levels of protective antibodies in people. The VRC studies confirm that volunteers who received only two doses of an inactivated H5N1 virus vaccine spaced 24 weeks apart produced only modest levels of H5N1-directed antibodies.