Vaccination of pigs with a DNA construct expressing an influenza virus M2-nucleoprotein fusion protein exacerbates disease after challenge with influenza A virus.
In mice, vaccines inducing antibodies to the extracellular domain of the M2 protein (M2e) can confer protection to influenza A virus infection. Unlike the surface glycoproteins, haemagglutinin and neuraminidase, this domain of M2 is highly conserved and is therefore a potential broad-spectrum immunogen. In this study, the protection conferred by vaccines inducing antibodies to M2e was evaluated in a challenge model for swine influenza in pigs. A protein resulting from the fusion between M2e and the hepatitis B virus core protein (M2eHBc), with or without adjuvant, was evaluated. In addition, a DNA construct expressing a fusion protein between M2e and influenza virus nucleoprotein (M2eNP) was evaluated to see if the broad-spectrum protection conferred by antibodies could be further enhanced by T helper cells and cytotoxic T cells. All vaccines induced an antibody response against M2e, and the M2eNP DNA vaccine additionally induced an influenza virus-specific lymphoproliferation response. However, after challenge with a swine influenza virus (H1N1), no protection was observed in the vaccinated groups compared with the non-vaccinated control group. On the contrary, vaccinated pigs showed more severe clinical signs than the control pigs. The M2eNP DNA-vaccinated pigs showed the most severe clinical signs and three out of six pigs died on days 1 and 2 post-challenge. These results indicate that antibodies to M2e, especially in combination with cell-mediated immune responses, exacerbate disease. Thus, clinical signs after infection should be observed closely in further studies using M2e as an immunogen and caution should be exercised in using M2e in humans.
Heinen
Paul P
PP
Division of Mammalian Virology, Institute for Animal Science and Health (ID-Lelystad), PO Box 65, 8200 AB Lelystad, The Netherlands1.
Rijsewijk
Frans A
FA
Division of Mammalian Virology, Institute for Animal Science and Health (ID-Lelystad), PO Box 65, 8200 AB Lelystad, The Netherlands1.
de Boer-Luijtze
Els A
EA
Division of Mammalian Virology, Institute for Animal Science and Health (ID-Lelystad), PO Box 65, 8200 AB Lelystad, The Netherlands1.
Bianchi
André T J
ATJ
Division of Mammalian Virology, Institute for Animal Science and Health (ID-Lelystad), PO Box 65, 8200 AB Lelystad, The Netherlands1.
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000503:physiopathology / Q000517:prevention & control / Q000662:veterinary*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000503:physiopathology / Q000517:prevention & control* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000662:veterinary; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000086082:Viroporin Proteins
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D009698:Nucleoproteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; C031540:M-protein, influenza virus; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins