Detection of anti-NS1 antibodies after pandemic influenza exposure: Evaluation of a serological method for distinguishing H1N1pdm09 infected from vaccinated cases

Anna Hayman Robertson; Milada Mahic; Miloje Savic; Gro Tunheim; Olav Hungnes; Lill Trogstad; Walter Ian Lipkin; Siri Mjaaland

doi:10.1111/irv.12712

Detection of anti-NS1 antibodies after pandemic influenza exposure: Evaluation of a serological method for distinguishing H1N1pdm09 infected from vaccinated cases

Influenza Other Respir Viruses. 2020 May;14(3):294-301. doi: 10.1111/irv.12712. Epub 2020 Jan 19.

Authors

Anna Hayman Robertson¹, Milada Mahic^{1

2}, Miloje Savic¹, Gro Tunheim^{1

3}, Olav Hungnes^{1

4}, Lill Trogstad¹, Walter Ian Lipkin², Siri Mjaaland^{1

2

3}

Affiliations

¹ Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
² Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, NY, USA.
³ KG Jebsen Center for Influenza Vaccine Research, Oslo, Norway.
⁴ WHO National Influenza Centre, Oslo, Norway.

Abstract

Background: Reliable exposure information is crucial for assessing health outcomes of influenza infection and vaccination. Current serological methods are unable to distinguish between anti-hemagglutinin (HA) antibodies induced by infection or vaccination.

Objectives: We aimed to explore an alternative method for differentiating influenza infection and vaccination.

Methods: Sera from animals inoculated with influenza viruses or purified H1N1pdm09 HA were obtained. Human samples were selected from a pregnancy cohort established during the 2009 H1N1 pandemic. Unvaccinated, laboratory-confirmed cases (N = 18), vaccinated cases without influenza-like-illness (N = 18) and uninfected, unvaccinated controls (N = 18) were identified based on exposure data from questionnaires, national registries and maternal hemagglutination inhibition (HI) titres at delivery. Animal and human samples were tested for antibodies against the non-structural protein 1 (NS1) and HA from H1N1pdm09, using a Luciferase Immunoprecipitation System (LIPS).

Results: Anti-NS1 H1N1pdm09 antibodies were detected in sera from experimentally infected, but not from vaccinated, animals. Anti-HA H1N1pdm09 antibodies were detectable after either of these exposures. In human samples, 28% of individuals with laboratory-confirmed influenza were seropositive for H1N1pdm09 NS1, whereas vaccinated cases and controls were seronegative. There was a trend for H1N1pdm09 NS1 seropositive cases reporting more severe and longer duration of symptomatic illness than seronegative cases. Anti-HA H1N1pdm09 antibodies were detected in all cases and in 61% of controls.

Conclusions: The LIPS method could differentiate between sera from experimentally infected and vaccinated animals. However, in human samples obtained more than 6 months after the pandemic, LIPS was specific, but not sufficiently sensitive for ascertaining cases by exposure.

Keywords: H1N1pdm09; NS1; influenza; pandemic; serology; vaccination.

Publication types

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

MeSH terms

Animals
Antibodies, Viral / blood*
Cohort Studies
Ferrets
Humans
Influenza A Virus, H1N1 Subtype / immunology*
Influenza A Virus, H1N1 Subtype / physiology
Influenza Vaccines / administration & dosage
Influenza Vaccines / adverse effects*
Influenza Vaccines / immunology
Influenza, Human / blood*
Influenza, Human / etiology*
Serologic Tests / methods*
Vaccination
Viral Nonstructural Proteins / immunology*

Substances

Antibodies, Viral
INS1 protein, influenza virus
Influenza Vaccines
Viral Nonstructural Proteins