Location: Virus and Prion ResearchTitle: Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies Author
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 3/14/2013
Publication Date: N/A
Citation: N/A Interpretive Summary:
Technical Abstract: Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs given whole-inactivated virus (WIV) influenza vaccine upon infection with an antigenically divergent virus. VAERD was first characterized with H1 viruses, and later described in pigs vaccinated with H3N2 WIV and challenged with heterologous H3N2, whereas live-attenuated virus vaccine (LAIV) was protective. An additional factor predisposing to H3N2 VAERD was maternally-derived antibodies (MDA) present at immunization. The present study was aimed at identifying immune correlates of VAERD and cross-protection. Piglets that acquired H3N2-specific MDA from immunized dams, along with seronegative controls, were vaccinated with WIV or LAIV (1 or 2 doses) and challenged with heterologous H3N2. Virus-binding IgG was detected in serum after WIV vaccination, but hemagglutination inhibition antibody titers remained very low. WIV induced low IgA and moderate IgG levels in lungs, but both responses were inhibited by MDA. Peripheral cellular responses following WIV were detected at modest levels, with evidence of MDA inhibition. LAIV elicited cross-reactive mucosal antibodies and T cells. While the presence of MDA at LAIV vaccination inhibited antibody production, it did not interfere with T cell priming. Piglets given 1 or 2 LAIV doses were protected against heterologous challenge. Lesions and clinical disease were more pronounced in WIV-vaccinated than control groups, and in contrast to previous studies, MDA did not accentuate H3N2 VAERD. High levels of mucosal antibodies were associated with protection, but LAIV was also protective in MDA-positive LAIV vaccinees that had reduced mucosal antibody responses. Since T cell responses were not inhibited by MDA, cellular immunity may have had a significant role in LAIV-mediated cross-protection. These data support LAIV as an influenza vaccine platform for the swine industry, as a single dose protected against heterologous challenge, even when administered to MDA-positive piglets.