Serum anti-neuraminidase antibody responses in human influenza A(H1N1)pdm09 virus infections

Herath M T K Karunarathna,Ranawaka A P M Perera,Vicky J Fang,Hui-Ling Yen,Benjamin John Cowling,Malik Peiris

doi:10.1080/22221751.2019.1572433

Herath M T K Karunarathna, Ranawaka A P M Perera + Show 4 more

Open Access

https://doi.org/10.1080/22221751.2019.1572433

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Abstract

ABSTRACT Haemagglutination inhibition (HAI) antibody titres are a correlate of protection for influenza virus infection, but several studies have also demonstrated the protective role of anti-neuraminidase (anti-NA) antibodies. However, there is limited data on anti-NA antibody responses in naturally occurring human influenza. We investigated anti-NA antibody responses to pandemic N1 and seasonal N1 in 18 RT–PCR-confirmed patients with naturally acquired pandemic influenza A (H1N1) 2009 disease detected as part of a prospective community study of influenza. There were increases in neuraminidase inhibition (NAI) antibody titres to both pandemic and seasonal N1 antigens, with greater fold increases in those who had low levels of anti-pandemic N1 titres in acute sera. Of 18 patients with pandemic H1N1 infection, fourfold increases in antibody were observed by HAI in 11 (61%) patients, by anti-pandemic N1 inhibition in 13 (72%) or either in 15 of them (83%). Prior seasonal H1N1 virus infections had elicited cross-reactive anti-pandemic N1 antibody titres in some people prior to the emergence of the 2009 pandemic H1N1 virus. Antibody responses to the anti-N1 pandemic 2009 virus and cross-reactive responses to anti-seasonal N1 antibody were seen in influenza A pandemic 2009 infections. NAI antibodies can complement HAI antibody in sero-diagnosis and sero-epidemiology.

Highlights

Influenza viruses pose global epidemic and pandemic threats [1]
Haemagglutination inhibition (HAI) antibody titres are a correlate of protection for influenza virus infection, but several studies have demonstrated the protective role of anti-neuraminidase antibodies
The effectiveness of the human influenza vaccine is primarily assessed by measuring serum anti-haemagglutinin (HA) antibody levels using the haemagglutination inhibition (HAI) assay and influenza vaccines are standardized by the amount of HA protein present in the vaccine formulation [6]

Summary

Introduction

Influenza viruses pose global epidemic and pandemic threats [1]. Influenza A virus epidemics lead to infection of millions of humans worldwide every year [2], while pandemics, which occur at unpredictable intervals, cause millions of human deaths [3,4]. The effectiveness of the human influenza vaccine is primarily assessed by measuring serum anti-haemagglutinin (HA) antibody levels using the haemagglutination inhibition (HAI) assay and influenza vaccines are standardized by the amount of HA protein present in the vaccine formulation [6]. Both the United States Food and Drug Administration and the European Medicines Agency Committee for Medicinal Products for Human Use define HAI titres of ≥40 as the 50% “protective” titre for influenza virus infection [7]. Recent data on seasonal influenza vaccination effectiveness have suggested that in some years vaccine protection was suboptimal, even though the vaccines met current seasonal vaccine standards and immunogenicity [11,12]

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