A universal flu vaccine?

Finally, some good news on the infectious disease front: In the near future, it may not be necessary to develop the flu vaccine every year. A study that saw the collaboration of groups of scientists from some of the main US research centers paves the way for the production of a potentially universal vaccine.

The study, published in the journal natures, describes a class of broad-spectrum neutralizing antibodies (broadly neutralizing antibodies, bnAbs) which recognizes an epitope in the region that anchors hemagglutinin (HA) to the membrane. HA is a critical target in the protection against influenza virus infections, but antibodies that recognize HA variable epitopes are only active against similar strains. Vaccines that preferentially elicit antibodies against conserved epitopes have therefore been studied for some time. The study in question fits exactly into this line of research.

American scientists have isolated more than 350 monoclonal antibodies from memory B lymphocytes (MBC) of subjects vaccinated or naturally infected with the H1 influenza virus. Molecular analysis allowed to identify some antibodies that bound an epitope located in the stem region (stalk) of the HA, near the anchor point to the membrane (anchor). Presumably this epitope is partially covered by the lipid membrane and could only be exposed when HA glycoprotein flexes. Tested in vitro the antibodies were extensively reactive and neutralizing against H1N1 and H1N2 viruses and showed cross-reactivity against H2 and H5 viruses. Additionally, the anti-anchor antibodies also neutralized viral mutants. In experiments live, anti-Anchor antibodies have been shown to be protective against lethal doses of H1 virus in mice. The researchers then went on to study how much anti-anchor antibodies were represented in the memory B lymphocyte repertoire of 20 subjects vaccinated with a vaccine targeting HA stalk. The antibodies of interest represented a substantial percentage, approximately 6%, of the entire pool. In the trial participants, the administration of an adjuvanted chimeric vaccine (cHA) was able to stimulate the production of antibodies against the anchor epitope.

"Our study highlights a broadly protective epitope of HA stalk and shows that humans have prior immunity against the anchor epitope of influenza virus and that vaccination can stimulate again the memory B lymphocytes to secrete antibodies against this epitope”. In addition to choosing the right target, however, attention must be paid to the wording. “The addition of the oil-in-water AS03 adjuvant was critical for activating MBC cells against the anchor epitope. Overall, our study shows that new vaccination strategies, such as the cHA vaccine with the AS03 adjuvant, have the ability to robustly induce antibodies against the unrecognized anchor epitope and may provide broad protection against H1 viruses.