For the week ending 10/25/25, flu activity in Philadelphia remains low but we are starting to detect some cases. Activity might start rising soon. 2/2

This was a collaborative project involving my lab, Boyd lab, Wilson lab, Ward lab, Le Sage lab, Martin lab, Monto lab, and Lakadawala lab supported by
@ceirrnetwork.bsky.social
Penn-CEIRR. Special thanks to
@cambupenn.bsky.social
student Grace Li for leading the effort. Such a cool story! 6/

Remarkably, we found that H1N1 viruses are now currently evolving within the human population to abrogate the binding of these antibodies. So, this antibody response was primed in the 1990s by H3, boosted recently with H1, and now H1N1 viruses are evolving to escape the response. Remarkable. 5/

We also found these H1/H3 cross-reactive antibodies in polyclonal sera, but only in samples from individuals born in the 1990s. Ferrets sequentially exposed to an H3N2 virus from the 1990s and a contemporary seasonal influenza vaccine produced the same type of H1/H3 cross-reactive antibodies. 4/

Even more surprising, we found that these cross-subtype antibodies targeted an HA head epitope that was partially conserved between H3N2 viruses from the 1990s and contemporary H1N1 viruses. 3/

We found that a large proportion of monoclonal antibodies isolated from individuals immunized with the 2021-22 seasonal influenza vaccine bound to an epitope on the HA head of both the H1N1 vaccine strain and H3N2 strains from the mid-1990s. 2/

Taken together, it is becoming clear that different influenza virus exposures in childhood elicit varying levels of long-lived cross-reactive HA and NA antibodies against newly emerging pandemic viruses. These data will be useful for risk assessment of new viral strains with pandemic potential. 5/5

These new NA studies complement our recent publication that demonstrates that immune imprinting (in that case, H1 or H2 infection) primes cross-reactive H5N1 HA antibody responses. 4/
www.nature.com/articles/s41...

While young children rarely possessed cross-reactive NA antibodies, we found that childhood infections with contemporary H1N1, but not H3N2, viruses can elicit them. 3/

We measured anti-NA antibodies in sera from 155 individuals born between 1927 and 2016 and found that those predicted to be 'imprinted' (i.e., initially infected) in childhood with H1N1 had higher levels of cross-reactive H5N1 NA antibodies compared to those imprinted with H2N2 or H3N2. 2/