Paul Thomas was merely trying to develop a more reliable test for exposure to avian influenza viruses when he made a fairly startling finding: Seasonal flu vaccines may protect individuals not only against the strains of flu they contain but also against many additional types.
An immunologist who works with T cell biology, Thomas hypothesized that T cell responses would provide greater specificity than antibody-based tests in terms of determining if an individual had been infected, because for a T cell response to be made, the virus has to have invaded the body. While this hypothesis turned out to be incorrect, his team did find among a group of bird scientists studied that those who reported receiving flu vaccines had a strong immune response not only against the seasonal H3N2 flu strain from 2010, when blood samples were collected for analysis, but also against flu subtypes never included in any vaccine formulation.
The results, published this week in mBio, are exciting “because it suggests that the seasonal flu vaccine boosts antibody responses and may provide some measure of protection against a new pandemic strain that could emerge from the avian population,” said Thomas, an Associate Member in the Department of Immunology at St. Jude Children’s Research Hospital in Memphis, Tenn. “There might be a broader extent of reactions than we expected in the normal human population to some of these rare viral variants.”
Because avian influenza viruses have an important role in emerging infections, Thomas and colleagues tested whether exposure to different types of birds can elicit immune responses to avian influenza viruses in humans. They studied blood samples from 95 attendees of the 2010 annual meeting of the American Ornithologist Union. They exposed plasma from the samples to purified proteins of avian influenza virus H3, H4, H5, H6, H7, H8 and H12 subtypes using ELISA and hemagglutination inhibition (HAI) to see how many different viruses participants reacted to, and how strongly.
In the ELISA tests, 77 percent of participants had detectable antibodies against avian influenza proteins. Most individuals had a strong antibody response to the seasonal H3N2 human virus-derived H3 subtype, part of the 2009-2010 vaccine. However, many also had strong measurable antibody responses to group 1 HA (avian H5, H6, H8, H12) and group 2 HA (avian H4, human H7) subtypes. Sixty-six percent of participants had some level of detectable antibodies against four or more HA proteins that sit on viral surfaces, and a few had responses to all subtypes tested, most of which have not previously been detected in humans.
The team also found that participants who had significant antibody responses did not necessarily also have significant T cell responses to avian viruses, indicating that these two immunity arms can be independently boosted after vaccination or infection; that individuals who reported receiving seasonal influenza vaccination had significantly higher antibodies to the avian H4, H5, H6, and H8 subtypes; and that participants with exposure to poultry had significantly higher antibody responses to the H7 subtype, but to no other subtypes. Exposure to other types of birds did not play a role in immunity.
A person’s immune response on the ELISA test did not necessarily predict response on the HAI test, and vice versa. As HAI antibodies only target the “head” of the HA while ELISA antibodies can be against the head or the relatively conserved “stalk” domain, this result indicated that some individuals were more likely to target the conserved stalk region (i.e. show greater reactivity in ELISA than in HAI).
The work has opened up a lot of questions in figuring out why people mount different types of responses, and potentially how the seasonal vaccine may play a role in boosting these responses, Thomas said. He has started additional studies in other groups of people with varied vaccination and infection histories to tease apart what exposures boost immunity against avian influenza viruses.