Abstract

BackgroundRecent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Therefore guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. To more fully characterize the model, antibody responses following either infection/re-infection with human influenza A/Wyoming/03/2003 H3N2 or immunization with its homologous recombinant hemagglutinin (HA) protein were studied.ResultsSerological samples were collected and tested for anti-HA immunoglobulin by ELISA, antiviral antibodies by hemagglutination inhibition (HI), and recognition of linear epitopes by peptide scanning (PepScan). Animals inoculated with infectious virus demonstrated pronounced viral replication and subsequent serological conversion. Animals either immunized with the homologous HA antigen or infected, showed a relatively rapid rise in antibody titers to the HA glycoprotein in ELISA assays. Antiviral antibodies, measured by HI assay, were detectable after the second inoculation. PepScan data identified both previously recognized and newly defined linear epitopes.ConclusionsInfection and/or recombinant HA immunization of guinea pigs with H3N2 Wyoming influenza virus resulted in a relatively rapid production of viral-specific antibody thus demonstrating the strong immunogenicity of the major viral structural proteins in this animal model for influenza infection. The sensitivity of the immune response supports the utility of the guinea pig as a useful animal model of influenza infection and immunization.

Highlights

  • Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses

  • Four groups of guinea pigs were chosen, (1) a negative control with no infection, (2) a positive control that received an infection only, (3) a group that was immunized with low dose of recombinant HA protein, and (4) another with high dose

  • Peak titers of progeny virus in this study occurred on day 3 and were in the range of 5 × 104 and 2 × 105 plaqueforming units/mL (pfu/mL) of nasal wash fluid (Long et al, in Immunization of Guinea Pigs The two immunized guinea pig groups (Groups 3 and 4) demonstrated similar patterns of increasing antibody titers over the course of the four recombinant HA protein inoculations

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Summary

Introduction

Recent and previous studies have shown that guinea pigs can be infected with, and transmit, human influenza viruses. Guinea pig may be a useful animal model for better understanding influenza infection and assessing vaccine strategies. Ferrets and macaques have increased tropisms to many primary influenza isolates but both are expensive to maintain and difficult to house Based largely on their recapitulation of human disease signs, ferrets have been used to derive serotyping reagents for assessing antigenic distance between isolates and potential vaccine strains. Guinea pigs are relatively inexpensive and easy to maintain for larger studies compared to ferrets and simians They are readily infected with primary isolates of human influenza strains, and have potential uses for virus evolutionary, prophylactic and therapeutic studies [3]. A recent study demonstrated acute viral replication and moderate virulence of the highly pathogenic 1918 pandemic and H5N1 viruses in addition to low-pathogenicity avian and human H1N1 viruses in guinea pigs [10]

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