Virus-neutralizing antibody response of mice to consecutive infection with human and avian influenza A viruses

Abstract

Summary. -In this work we simulated in a mouse model a naturally occurring situation of humans, who overcame an infection with epidemic strains of influenza A, and were subsequently exposed to avian influenza A viruses (IAV). The antibody response to avian IAV in mice previously infected with human IAV was analyzed. We used two avian IAV (A/Duck/Czechoslovakia/1956 (H4N6) and the attenuated virus rA/Viet Nam/1203-2004 (H5N1)) as well as two human IAV isolates (virus A/Mississippi/1/1985 (H3N2) of medium virulence and A/Puerto Rico/8/1934 (H1N1) of high virulence). Two repeated doses of IAV of H4 or of H5 virus elicited virus-specific neutralizing antibodies in mice. Exposure of animals previously infected with human IAV (of H3 or H1 subtype) to IAV of H4 subtype led to the production of antibodies neutralizing H4 virus in a level comparable with the level of antibodies against the human IAV used for primary infection. In contrast, no measurable levels of virus-neutralizing (VN) antibodies specific to H5 virus were detected in mice infected with H5 virus following a previous infection with human IAV. In both cases the secondary infection with avian IAV led to a significant increase of the titer of VN antibodies specific to the corresponding human virus used for primary infection. Moreover, cross-reactive HA2-specific antibodies were also induced by sequential infection. By virtue of these results we suggest that the differences in the ability of avian IAV to induce specific antibodies inhibiting virus replication after previous infection of mice with human viruses can have an impact on the interspecies transmission and spread of avian IAV in the human population.Keywords: avian influenza A viruses; sequential influenza A infection; antibody response; virus-neutralizing antibodies; HA2-specific antibodies; original antigenic sin * Corresponding author. E-mail: viruevar@savba.sk; phone: +421-2-59302427. Abbreviations: HA = hemagglutinin; IAV = influenza A virus; MAb = monoclonal antibody; OAS = original antigenic sin; VN = virus-neutralizing

Immune response of mice to non-adapted avian influenza A virus

“…Avian infl uenza virusA/Duck/Czechoslovakia/1956 (H4N6) (A/Duck) isolated from wild ducks in Czechoslovakia and human virus A/Mississippi/1/85 (H3N2) (A/Miss) originated from the collection of viruses at the Institute of Virology, Slovak Academy of Sciences, Bratislava, Slovak Republic. Viruses were propagated in embryonated chicken eggs as usually (Janulíková et al, 2015).…”

“…Th e VN ability of specifi c antibodies present in sera of mice exposed to A/Duck virus was evaluated by modifi ed rapid culture assay (RCA) according to the protocol described before (Janulíková et al, 2015), using 8 TCID 50 of A/Duck virus and horseradish peroxidase conjugate of monoclonal antibody specifi c to NP of IAV (107L-Px) (Tkáčová and Varečková, 1996).…”

“…Human virus A/Miss was adapted to mice as described before ). Avian infl uenza virus A/Duck could not be adapted to mice (Janulíková et al, 2015). A non-mouse-adapted A/Duck virus was therefore used in all experiments.…”