Neuraminidase Antibody Response to Homologous and Drift Influenza a Viruses After Immunization with Seasonal Influenza Vaccines

Neuraminidase (NA)-based immunity could reduce the severity of infection caused by the new antigenic variants of influenza viruses. Detection of NA-inhibiting (NI) antibodies simultaneously with antibodies to hemagglutinin (HA) may enhance research of antibody response to influenza vaccines. Methods. The study examined 64 pairs of sera from patients vaccinated in 2018 with seasonal inactivated trivalent influenza vaccines (IIVs) with the formula recommended by WHO for the 2018-2019 influenza season. Antibodies to drift influenza viruses A/Guangdong-Maonan/SWL1536/2019(H1N1)pdm09 and A A/Brisbane/34/2018(H3N2) were studied before vaccination and 21 days after vaccination. To assess NI antibodies, we used the enzyme-linked lectin assay (ELLA) with pairs of reassortant viruses A/H6N1 and A/H6N2, and anti-HA antibodies were detected in hemagglutination inhibition (HI) test. The microneutralization (MN) test was performed in the MDCK cell line with A/H6N1 and A/H6N2 viruses. Results. Seasonal IIVs induce a substantial immune response of NI antibodies to influenza A/H1N1pdm09 and A/H3N2 viruses. A significantly reduced ‘herd’ immunity to drift influenza viruses A/H1N1pdm09 and A/H3N2 was shown, compared to previously circulating strains, but most of all to N2. Seasonal IIVs caused increases in antibodies to homologous and drift viruses, but to drift viruses more often among older patients. The level of NI antibodies to later A/H1N1pdm09 virus in response to IIVs was statistically significantly lower among younger people. After IIV vaccination, the total proportions of individuals with HI antibody levels ≥1:40 and NI antibodies ≥ 1:20 were 32.8% to drift A/H1N1pdm09 virus and 17.2% to drift A/H3N2 virus. Antisera containing HI and NI antibodies exhibit neutralizing properties in vitro against viruses with unrelated HA of H6 subtype. Conclusions. Drift A/H1N1pdm09 and A/H3N2 viruses demonstrated significantly lower reactivity with NI and NI antibodies to early influenza viruses. In response to seasonal IIVs, the level of seroprotection increased, including to drift viruses A, but to a greater extent to A/H1N1pdm09. Based on the data obtained, it can be hypothesized that in the case of a mismatched HA, it will most likely be necessary to vaccinate against the N1-containing influenza virus those who under 60 years of age, and the entire population against virus possessing N2.