Enhanced pneumonia and disease in pigs vaccinated with an inactivated human-like (δ-cluster) H1N2 vaccine and challenged with pandemic 2009 H1N1 influenza virus

Abstract

Influenza is an economically important respiratory disease affecting swine world-wide with potential zoonotic implications. Genetic reassortment and drift has resulted in genetically and antigenically distinct swine influenza viruses (SIVs). Consequently, prevention of SIV infection is challenging due to the increased rate of genetic change and a potential lack of cross-protection between vaccine strains and circulating novel isolates. This report describes a vaccine-heterologous challenge model in which pigs were administered an inactivated H1N2 vaccine with a human-like (δ-cluster) H1 six and three weeks before challenge with H1 homosubtypic, heterologous 2009 pandemic H1N1. At necropsy, macroscopic and microscopic pneumonia scores were significantly higher in the vaccinated and challenged (Vx/Ch) group compared to non-vaccinated and challenged (NVx/Ch) pigs. The Vx/Ch group also demonstrated enhanced clinical disease and a significantly elevated pro-inflammatory cytokine profile in bronchoalveolar lavage fluid compared to the NVx/Ch group. In contrast, viral shedding and replication were significantly higher in NVx/Ch pigs although all challenged pigs, including Vx/Ch pigs, were shedding virus in nasal secretions. Hemagglutination inhibition (HI) and serum neutralizing (SN) antibodies were detected to the priming antigen in the Vx/Ch pigs but no measurable cross-reacting HI or SN antibodies were detected to pandemic H1N1 (pH1N1). Overall, these results suggest that inactivated SIV vaccines may potentiate clinical signs, inflammation and pneumonia following challenge with divergent homosubtypic viruses that do not share cross-reacting HI or SN antibodies.

Live Attenuated Influenza Vaccine Provides Superior Protection from Heterologous Infection in Pigs with Maternal Antibodies without Inducing Vaccine-Associated Enhanced Respiratory Disease

“…Strikingly, macroscopic lung lesions were exacerbated ( Fig. 4B and 5C) in a manner similar to that in another VAERD model (4,5,25). Composite microscopic lung and tracheal lesions ( Fig.…”

“…A concern with inactivated adjuvanted IAV vaccines is the phenomenon of vaccine-associated enhanced respiratory disease (VAERD) (4,5,8,25). This phenomenon is associated with the use of vaccines containing a virus of the same hemagglutinin subtype as the subsequent challenge strain, but with substantial antigenic drift.…”

“…This phenomenon is associated with the use of vaccines containing a virus of the same hemagglutinin subtype as the subsequent challenge strain, but with substantial antigenic drift. Our group recently described VAERD in association with the use of a vaccine containing a human-like delta cluster H1N2 antigen followed by challenge with the 2009 pandemic H1N1 virus (5). A consistent predisposing factor for VAERD is the presence of IgG antibodies that cross-react with the heterologous virus but lack the ability to neutralize infectivity.…”

Influenza A Virus Infections in Swine

“…The researchers speculate that the potential may exist for similar vaccineassociated disease enhancement in humans. 33 …”

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“…The negative role of the cross-reactive neutralizing antibodies to the HA stem region in vivo was shown during the repeated infection by the antigenically heterologous influenza virus. The enhancement of the respiratory tract infection was recorded after the vaccination of animals and humans with the inactivated vaccine and consequent infection by the heterological influenza strain [57][58][59][60]. Thus after the double immunization of pigs by whole virion inactivated vaccine against H1N1 virus with adjuvant, the enhancement of the lung pathology was recorded in case of a consequent infection by H1N1pdm09 virus.…”