POINT MUTATIONS ON THE HEMAGGLUTININ OF THE 2015-2016 H1N1 LIVE ATTENUATED INFLUENZA VACCINE STRAIN AND THEIR EFFECT ON VIRAL REPLICATION
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Date
2022-05-04
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Johns Hopkins University
Abstract
The H1N1 component of the FluMist quadrivalent live attenuated influenza vaccine (QLAIV) for the 2015-2016 flu season had a lower replicative fitness in comparison to the other components in the formulation. This contributed to the low vaccine effectiveness of the 2015–16 A/H1N1pdm09 component, leading to the loss of the Advisory Committee on Immunization Practices recommendation for use. For the 2019-2020 flu season, A/Slovenia/2903/15 (A/Slov-15) was used as a replacement and showed higher vaccine effectiveness than the original A/Bolivia/559/2013 (A/Bol-13). The two vaccine strains are different in only 4 amino acids on their Hemagglutinin (HA) proteins. We investigated the impact of these 4 residues on virus replication by generating recombinant A/Bol-13 viruses that have individually changed these 4 amino acid positions to the ones present in A/Slov-15. On MDCK cells, at both 33 and 37 degrees Celsius, the reproduction rate & plaque-forming ability of the S84N and S162N mutant strains closely resemble A/Slov-15 while the I216T and P271Q mutants remain similar to A/Bol-13. S84N, S162N, and I216T exhibit a similar trend on hNEC cell; however, we failed to come to a conclusion on the phenotype of P271Q. Our data indicate that two of the four amino acid differences between the A/Slov-15 and A/Bol-13 HA proteins may have adverse effects on virus replication.
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Keywords
Influenza, LAIV, Vaccine, Flu, H1N1, FluMist