Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

Eric A Lefevre,Munir Iqbal,Ruth A Elderfield,Mick Bailey,Fanny Garcon,Sharon M Brookes,B Veronica Carr,Bryan Charleston,Ian H Brown,Wendy S Barclay,Charlotte F Inman,Helen Prentice,Simon Gubbins,Michelle L Hill,Yi Guan

doi:10.1371/journal.pone.0032400

Abstract

Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4−CD8+ (cytotoxic) and CD4+CD8+ (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.

Highlights

In June 2009, the World Health Organization (WHO) declared an H1N1 influenza pandemic in response to the emergence and global spread of a novel H1N1 influenza A virus - A(H1N1)pdm/ 09, which contained a unique combination of gene segments derived from multiple viruses that have been circulating in pigs for decades [1]
In the UK, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain (Cal07) were used for the national immunisation programme: (i) Pandemrix (GlaxoSmithKline Biologicals S.A., GSK), an AS03b-adjuvanted split virion vaccine derived from embryonated chicken eggs, administered once in healthy adults, and (ii) Celvapan (Baxter AG), a nonadjuvanted whole virion vaccine derived from Vero cell culture, administered twice with a minimum of 3 weeks between injections
Pigs vaccinated with the adjuvanted split vaccine produced significantly more specific IgG1 antibodies after one vaccination, compared to those vaccinated with the nonadjuvanted whole vaccine (20.6160.14LogEU versus 22.3360.09LogEU at day 21pv, respectively, P,0.05, n = 3)

Summary

Introduction

In June 2009, the World Health Organization (WHO) declared an H1N1 influenza pandemic in response to the emergence and global spread of a novel H1N1 influenza A virus - A(H1N1)pdm/ 09 (http://www.who.int/mediacentre/news/statements/2009/ h1n1_pandemic_phase6_20090611/en/index.html), which contained a unique combination of gene segments derived from multiple viruses that have been circulating in pigs for decades [1]. In the UK, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain (Cal07) were used for the national immunisation programme: (i) Pandemrix (GlaxoSmithKline Biologicals S.A., GSK), an AS03b-adjuvanted split virion vaccine derived from embryonated chicken eggs, administered once in healthy adults, and (ii) Celvapan (Baxter AG), a nonadjuvanted whole virion vaccine derived from Vero cell culture, administered twice with a minimum of 3 weeks between injections These A(H1N1)pdm/09 vaccines were authorized under ‘‘Exceptional Circumstances’’ on the basis of limited to very limited safety and immunogenicity data obtained with these A(H1N1)pdm/09 influenza vaccines and utilised more complete safety and immunogenicity data obtained with H5N1 ‘‘mock-up’’ vaccines e.g. similar versions of the A(H1N1)pdm/09 vaccines that contain the whole H5N1 A/Vietnam/1203/2004 influenza virus for the non-adjuvanted whole vaccine or the viral surface protein haemagglutinin (HA) derived from H5N1 A/Vietnam/1194/ 2004 for the adjuvanted split vaccine Since these A(H1N1)pdm/09 vaccines were made available, several authors have reported that both were strongly immunogenic in adults and/or children [4,5]

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