Abstract

BackgroundPre-existing antibodies to influenza virus neuraminidase may provide protection against infection influenza viruses containing novel hemagglutinin (HA). The aim of our study was to evaluate serum neuraminidase-inhibiting (NI) antibodies against А/California/07/2009(H1N1) [H1N1/2009pdm] and А/New Caledonia/20/1999(H1N1) [H1N1/1999] influenza viruses in relation with the age of participants and hemagglutination-inhibition (HI) antibody levels. Anti-H1N1/2009pdm neuraminidase and anti-H1N1/1999 neuraminidase antibody levels were measured in total 219 serum samples from Russian healthy peoples of various ages examined before and a year after pandemic strain appearance. We adjusted peroxidase-linked lectin micro-procedure to measure NI antibody titers using the reassortant A/H7N1 influenza viruses based on A/equine/Prague/1/56(H7N7). Also, HI antibody titers were estimated against H1N1/2009pdm, H1N1/1999 and a panel of seasonal A/H1N1 influenza viruses.ResultsIn sera samples collected during the fall of 2010, mean titers of specific HI and NI antibodies to H1N1/2009pdm were 2–2.1 times lower than antibody levels against H1N1/1999. Of the 163 individuals examined, 58 (35.6%) had NI anti-H1N1/2009pdm antibody titers > 1:20, compared to 93 (57.1%) who had NI anti-H1N1/1999 antibody titers > 1:20. There were low correlations between HI and NI antibody levels against either H1N1/1999 or H1N1/2009pdm in the same serum samples. The 24 adults born between 1957 and 1977 expressed very low levels of NI antibodies to A/H1N1 influenza viruses. Persons with low HI anti-H1N1/2009pdm titers but positive to seasonal A/H1N1 demonstrated significantly higher NI anti-A/H1N1 antibody titers than unexposed subjects. In 2005 cross-reactive NI anti-H1N1/2009pdm antibody titers > 1:20 were detected among 7.1% of young people.ConclusionsOur study confirmed that contact with seasonal influenza viruses may have contributed to generating the cross-reacting anti-H1N1/2009pdm NI antibodies which were detected in the sera of 18-20 years old people examined before the pandemic virus active circulation. The lowest levels of antibodies to the neuraminidase of N1 subtype were in the group of participants born during the circulation of influenza A/H2N2 or A/H3N2 viruses. The low correlation between HI and NI antibody titers suggests that NI antibody detection can be used as an additional test to evaluate the immune response after influenza infections or immunizations.

Highlights

  • Pre-existing antibodies to influenza virus neuraminidase may provide protection against infection influenza viruses containing novel hemagglutinin (HA)

  • Chi-square test’s p-value < 0.001 suggested a statistically significant relationship between HI and NI antibody levels against each A/H1N1 in the same serum samples, the correlation was rather low (Spearman rs = 0.32 [95% CI: 0.11–0.57], and rs = 0.29 [95% CI: 0.01– 0.54], in case of H1N1/1999 and H1N1/2009pdm respectively)

  • To determine a possible origin of NI antibodies against H1N1/2009pdm, we evaluated antibody titers ≥1:40 supposed to be protective in three groups separated on the basis of pre-existing HI antibody levels against H1N1/ 2009pdm and seasonal A/H1N1 viruses (n = 159, 4 sera were excluded from analysis because there was no HI data with all tested A/H1N1 antigens)

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Summary

Introduction

Pre-existing antibodies to influenza virus neuraminidase may provide protection against infection influenza viruses containing novel hemagglutinin (HA). Anti-H1N1/2009pdm neuraminidase and anti-H1N1/1999 neuraminidase antibody levels were measured in total 219 serum samples from Russian healthy peoples of various ages examined before and a year after pandemic strain appearance. Several animal studies, including a plasmid DNA vaccine model, suggest that NI antibodies could provide partial protection from lung infection and even from lethal challenge with highly pathogenic А/H5N1 influenza viruses [4,5,6,7]. It was shown that immunization with seasonal influenza strains induced cross-reactive serum antibody to the NA of antigenically distinct H1N1/2009pdm, mostly in elderly individuals [9,10]

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