Immune correlates of clinical outcomes in maternal antibody-positive piglets vaccinated with attenuated or killed SIV and challenged with an antigenic variant

OBJECTIVES OF THE STUDY.
Current SIV vaccines, which contain whole inactivated virus (WIV), do not provide broad cross-protection against new variants, and maternal antibodies inhibit pigs’ immune response to vaccination. Intranasal vaccination of pigs with a live attenuated influenza virus (LAIV) is considered likely to induce more cross-reactive T cells and respiratory tract antibodies capable of providing broad protection. Objectives of the study were the following:
1. Compare the effects of maternally-derived antibodies on antibody and T cell responses to intranasal LAIV versus intramuscular WIV vaccines.
2. Test the efficacy of one LAIV dose versus the two-dose LAIV regimen tested previously.
3. Identify immune mechanisms that correlate with the cross-protective property of LAIV vaccine.
4. Identify immune mechanisms which correlate with vaccine-associated respiratory disease (VAERD).

RESULTS
Weaned piglets, with and without maternal antibodies, were immunized with LAIV or WIV. Neither vaccine induced high serum hemagglutination inhibition antibody titers. Pigs that received LAIV had greater T cell responses and higher levels of lung antibodies. Antibody responses were reduced in pigs with maternal antibodies, while T cell responses were not inhibited. Pigs were experimentally infected with an H3N2 virus mismatched to the vaccines. LAIV vaccine provided strong cross-protection, even in pigs that had maternal antibodies, in terms of lung lesions, virus replication, and clinical disease. Pigs that had received the WIV vaccine were not protected against challenge infection, but had enhanced clinical disease and lung lesions. The presence of maternal antibodies at vaccination did not significantly affect disease severity. Immune factors associated with protection included IgA antibodies in the respiratory tract and virus-specific T cells in lymphoid tissue. The results support LAIV as an influenza vaccine platform for the swine industry, since a single dose protected against the mismatched challenge strain even when administered to pigs with maternal antibodies.

* P.I. Contact Information: 2120 Vet Med, Ames, IA 50011. Telephone 515-294-8072. Email [email protected].