Canaday LM, Resnick JD, Liu H, Powell H, McCoy AM,. HA and M2 sequences alter the replication of 2013-16 H1 live attenuated influenza vaccine infection in human nasal epithelial cell cultures. Vaccine. 2022 Jun 16:S0264-410X(22)00733-2
From 2013 to 2016, the H1N1 component of live, attenuated influenza vaccine (LAIV) performed very poorly in contrast to the inactivated influenza vaccine. We utilized a primary, differentiated human nasal epithelial cell (hNEC) culture system to assess the replication differences between isogenic LAIVs containing the HA segment from either A/Bolivia/559/2013 (rBol), which showed poor vaccine efficacy, and A/Slovenia/2903/2015 (rSlov), which had reasonable vaccine efficacy. There were minimal differences in infectious virus production in Madin-Darby Canine Kidney (MDCK) cells, but the rSlov LAIV showed markedly improved replication in hNEC cultures at both 32 °C and 37 °C, demonstrating that the HA segment alone could impact LAIV replication in physiologically relevant systems. The rSlov-infected hNEC cultures showed stronger production of interferon and proinflammatory chemokines which might also be contributing to the increased overall vaccine effectiveness through enhanced recruitment and activation of immune cells. An M2-S86A mutation had no positive effects on H1 LAIV replication in hNEC cultures, in contrast to the increased infectious virus production seen in an H3 LAIV. No obvious defects in viral RNA packaging were detected, suggesting that HA function, rather than defective particle production, may be driving the differential infectious virus production in hNEC cultures. Overall, we have shown that not all H1 HA segments can be successfully used in LAIV, and this phenotype cannot be fully explained by segment incompatibilities. Physiologically relevant temperatures and primary cell cultures should be used to demonstrate that candidate LAIVs can replicate efficiently, which is a necessary property for effective vaccines.
See Also:
Latest articles in those days:
- The bat-borne influenza A virus H9N2 exhibits a set of unexpected pre-pandemic features 15 hours ago
- Neutralizing and protective murine monoclonal antibodies to the hemagglutinin of influenza H5 clades 2.3.2.1 and 2.3.4.4 15 hours ago
- Phylogenetic analysis of HA and NA genes of influenza A viruses in immunosuppressed inpatients in Beijing during the 2018-2020 influenza seasons 24 hours ago
- The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection 24 hours ago
- Engineering an Optimal Y280-Lineage H9N2 Vaccine Strain by Tuning PB2 Activity 24 hours ago
[Go Top] [Close Window]