Project Number: 3625-32000-108-11
Project Type: Reimbursable

Start Date: Feb 02, 2012
End Date: Jan 31, 2014

Objective:
1. Determine if antibodies elicited by an inactivated vaccine predispose pigs for enhanced disease when infected with the heterologous panH1N1 virus. The working hypothesis of this aim is that vaccination elicits IgG antibodies that do not neutralize the challenge virus but trigger greater inflammation of the infected lungs. 2. Determine if mismatch between viral surface antigens of vaccine and challenge strains is sufficient to cause enhanced disease following challenge. The working hypothesis is that disease enhancement primed by the heterologous vaccine stems from antigenic differences in the highly variable HA and/or NA envelope proteins.

Approach:
We will determine if antibodies induced by heterologous H1 virus vaccination are sufficient to predispose pigs for enhanced disease after panH1N1 infection. We will test our working hypothesis using an experimental approach of passively immunizing pigs followed by heterologous panH1N1 inoculation. The rationale for this aim is that completing it will reveal whether a systemic antibody response creates susceptibility to enhanced disease. The additional experimental approach is to generate two virus-like particle (VLP) vaccines that bear HA, NA, and M1 proteins of either MN08 or CA09. Adjuvanted vaccines will be formulated from the two VLP’s, with HA activity calibrated to match the corresponding inactivated whole-virus vaccines. We will analyze the cross-reactivity of antibodies and T cells induced by each VLP and whole-virus vaccine, and test the protective or enhancing effects on CA09 challenge. The rationale for this aim is that it will reveal whether viral envelope proteins in an inactivated H1 vaccine trigger the pathogenic immune response to heterologous panH1N1 infection. Findings from this work will aid future efforts to identify specific epitopes and immune mechanisms pivotal to the problem. Outcomes will provide insight into the safety and efficacy of VLP and other subunit forms of IAV vaccine, when vaccinates encounter antigenically divergent zoonotic strains. Animal studies will be conducted at the NADC; blood and tissue samples will be processed to access humoral and cell mediated immune response to vaccine. Post-challenge, samples will be processed at NADC for bacteriologic, virologic, and histologic studies to assess virus replication and pathology in various porcine tissues. Blood samples will also be given to our collaborators to perform the cell mediated immune assays.