Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals

Abstract

The main objective of the study was to evaluate neuraminidase inhibiting (NI) antibodies against A/H1N1pdm09 influenza viruses in the community as a whole and after infection. We evaluated NI serum antibodies against A/California/07/09(H1N1)pdm and A/South Africa/3626/2013(H1N1)pdm in 134 blood donors of different ages using enzyme-linked lectin assay and in 15 paired sera from convalescents with laboratory confirmed influenza. The neuraminidase (NA) proteins of both A/H1N1pdm09 viruses had minimal genetic divergence, but demonstrated different enzymatic and antigenic properties. 5.2% of individuals had NI antibody titers ≥1:20 against A/South Africa/3626/2013(H1N1)pdm compared to 53% of those who were positive to A/California/07/2009(H1N1)pdm NA. 2% of individuals had detectable NI titers against A/South Africa/3626/13(H1N1)pdm and 47.3% were positive to A/California/07/2009(H1N1)pdm NA among participants negative to hemagglutinin (HA) of A/H1N1pdm09 but positive to seasonal A/H1N1. The lowest NI antibody levels to both A/H1N1pdm09 viruses were detected in individuals born between 1956 and 1968. Our data suggest that NI antibodies against A/South Africa/3626/13 (H1N1)pdm found in the blood donors could have resulted from direct infection with a new antigenic A/H1N1pdm09 variant rather than from cross-reaction as a result of contact with previously circulating seasonal A/H1N1 variants. The immune responses against HA and NA were formed simultaneously right after natural infection with A/H1N1pdm09. NI antibodies correlated with virus-neutralizing antibodies when acquired shortly after influenza infection. A group of middle-aged patients with the lowest level of anti-NA antibodies against A/California/07/2009 (H1N1)pdm was identified, indicating the highest-priority vaccination against A/H1N1pdm09 viruses.

Exploitation of glycosylation in enveloped virus pathobiology

“…Current influenza vaccines poorly display NA epitopes and do not produce robust anti-NA antibodies [106], whilst during infection many NA-reactive B cells and antibodies are produced. The development of recombinant influenza vaccines, which improve the display of influenza NA, may provide a method of vaccine optimisation to improve targeting of NA for broader protection against divergent influenza strains circulating in human populations [[106], [107], [108]].…”

Study of Neuraminidase-Inhibiting Antibodies in Clinical Trials of Live Influenza Vaccines

“…Not surprisingly, the level of collective immunity to A/California/7/09(H1N1)pdm09 was, by 2016, significantly higher than that to A/South Africa/3626/13(H1N1)pdm09. It was shown that, in the 2015-2016 epidemic season, the levels of NI antibodies ≥1:40 to A/California/7/09(H1N1)pdm09 amounted to about 30% [23].…”

Study of Antibodies to Influenza Neuraminidase N2

“…Thus, in the same sera, NI antibody titers ≥1:20 to A/Victoria/361/2011(H3N2) and A/Hong Kong/4801/2014(H3N2) viruses occurred simultaneously in only 10% of cases. In our early studies, it was shown that changes in several amino acids affected the enzymatic activity and antigenic properties of N1 of A/California/07/2009(H1N1)pdm09 and A/South Africa/3626/13(H1N1)pdm09 [ 21 ]. Interestingly, the A/Victoria/361/2011(H3N2) virus has lysine (K) in position 258, and A/Hong Kong/4801/2014(H3N2) virus and other epidemic viruses have glutamic acid (E).…”