A neuraminidase activity-based microneutralization assay for evaluating antibody responses to influenza H5 and H7 vaccines

Hui Zhao; Kangwei Xu; Zheng Jiang; Ming Shao; Shuzhen Liu; Xuguang Li; Junzhi Wang; Changgui Li

doi:10.1371/journal.pone.0207431

A neuraminidase activity-based microneutralization assay for evaluating antibody responses to influenza H5 and H7 vaccines

PLoS One. 2018 Nov 15;13(11):e0207431. doi: 10.1371/journal.pone.0207431. eCollection 2018.

Authors

Hui Zhao¹, Kangwei Xu¹, Zheng Jiang¹, Ming Shao¹, Shuzhen Liu¹, Xuguang Li^{2

3}, Junzhi Wang¹, Changgui Li¹

Affiliations

¹ Division of Viral Vaccine III, National Institutes for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, P.R. China.
² Center for Biologics Evaluation, Ottawa, Biologics and Genetic Therapies Directorate, Health Canada and WHO Collaborating Center for Standardization and Evaluation, Ottawa, Canada.
³ Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.

Abstract

Outbreaks of the highly pathogenic avian influenza H5N1 and H7N9 viruses have spurred an unprecedented research effort to develop antivirals and vaccines against influenza. Standardized methods for vaccine evaluation are critical for facilitating vaccine development. Compared with hemagglutination inhibition assays, mounting evidence suggest that microneutralization tests (MNTs) is a better choice for the evaluation of candidate pandemic influenza vaccines because they measure neutralizing antibody activity in cell cultures and are more sensitive in detecting H5 and H7. Here, we report a MNT measuring neuraminidase activity as the read-out (NA-MNT) for quantitative analysis of neutralizing antibodies against avian influenza viruses. Compared to the conventional microneutralization assay (ELISA-MNT), the NA-MNT is faster with lower intra- and inter-assay variations, while no difference in geometric mean titers was found between these two assays for the evaluation of H5N1 and H7N9 vaccines. These results suggest that NA-MNT is a reliable and high throughput method which could facilitate the development of candidate pandemic influenza vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / genetics
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
Antibody Formation / immunology
Birds / virology
Hemagglutinin Glycoproteins, Influenza Virus
Humans
Influenza A Virus, H5N1 Subtype / immunology*
Influenza A Virus, H5N1 Subtype / pathogenicity
Influenza A Virus, H7N9 Subtype / immunology*
Influenza A Virus, H7N9 Subtype / pathogenicity
Influenza Vaccines / immunology*
Influenza in Birds / immunology
Influenza in Birds / virology
Influenza, Human / genetics
Influenza, Human / immunology*
Influenza, Human / virology
Neuraminidase / genetics
Neuraminidase / immunology
Pandemics
Vaccines, Inactivated / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Hemagglutinin Glycoproteins, Influenza Virus
Influenza Vaccines
Vaccines, Inactivated
Neuraminidase

Grants and funding

This work was supported by Beijing Municipal Natural Science Foundation (CN) (grant no 7173277) and the National Science and Technology Major Projects (grant no 2012ZX10002006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.