The bird flu (avian H5N1 influenza) has been circulating widely in cattle and other mammals. Many researchers note that there is a risk of a human pandemic. Some studies suggest that older humans are more resistant to H5N1 infections. The hypothesis is that the immunity is due to childhood imprinting with other group 1 viruses (H1N1 and H2N2). However, the underlying immunological mechanism is poorly understood.
Now, new work suggests that prior exposure to specific types of seasonal influenza viruses promotes cross-reactive immunity against the H5N1 avian influenza virus.
Older adults who were exposed to seasonal flu viruses that circulated prior to 1968 were found to be more likely to have antibodies that bind to the H5N1 avian flu virus. The findings suggest that younger adults and children would benefit more from H5N1 vaccines, even those not tailored specifically to the current strain circulating in birds and cattle.
This work is published in Nature Medicine in the paper, “Immune history shapes human antibody responses to H5N1 influenza viruses.”
“We know that early childhood influenza exposures can elicit immune responses that last a lifetime,” said Scott Hensley, PhD, professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania. “We found that antibody responses that were primed by H1N1 and H3N2 viruses decades ago can cross-react to H5N1 avian viruses circulating today. Most of these cross-reactive antibodies cannot prevent infections, but they will likely limit disease if we have an H5N1 pandemic.”
H5N1 viruses have circulated in birds for many years, but a new version—clade 2.3.4.4b H5N1 virus—emerged more recently and has since spread among cattle. This current H5N1 strain does not bind well to receptors in the human upper airway, but widespread circulation in mammals could lead to mutations that help the virus infect human airway cells and increase transmission. If this occurs, H5N1 could potentially start human-to-human transmission.
Researchers measured H5N1 antibody responses in sera from 157 individuals born between 1927 and 2016. They found that blood samples from older adults born prior to 1968 who were likely first exposed to H1N1 or H2N2 in childhood had higher levels of antibodies that could bind to the H5N1 virus. An individual’s birth year was closely linked to the amount of H5N1-fighting antibodies in their blood. Young children who were not exposed to seasonal flu viruses possessed low levels of antibodies that could fight H5N1.
Researchers also obtained blood samples from a separate group of individuals born between 1918 and 2003 before and after they were vaccinated with a 2004 H5N1 vaccine (A/Vietnam/1203/2004 H5N1 vaccine). Both younger and older humans produced H5-reactive antibodies to the A/Vietnam/1203/2004 vaccine strain and to a contemporary clade 2.3.4.4b strain. There were “higher seroconversion rates in young children who had lower levels of antibodies before vaccination,” noted the authors. These antibodies bound to both the 2004 H5N1 virus and to the clade 2.3.4.4b H5N1 virus that is circulating today.
“In the event of an H5N1 pandemic, all age groups will likely be highly susceptible, but it is possible that the highest disease burden will be in children,” said Hensley. “If this is the case, children should be prioritized for H5N1 vaccinations.”