Prevention of heterologous Porcine Reproductive and Respiratory Syndrome Virus (PRRSv) infection using an antibody-virus complex vaccine

Hemnani, Khushboo
Major Professor
Jessie D. Trujillo
Committee Member
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Biomedical Sciences
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Biomedical Sciences

Porcine Reproductive and Respiratory Syndrome virus (PRRSv) continues to cause critical issues for the swine industry worldwide, with an estimated loss of $1billion annually in the United States. PRRSv is a genetically diverse RNA Arterivirus with up to 20% variability. Available vaccines, mainly modified-live and autogenous, provide limited protection against divergent strains. Additionally, PRRSv immune dysregulation, and immune evasion strategies pose huge challenges in the successful development of cross-protective vaccines. A vital immune evasion strategy utilized is termed deceptive imprinting. Many pathogens contain highly immunodominant, commonly variable, non-protective or partially protective antigenic determinants termed "decoys". Decoys subvert host immune responses away from conserved, cross protective and critical viral determinants leading to poor vaccine performance. In attempt to subvert immunodominance of decoys, by masking decoys with PRRSv specific antibodies, we hypothesize virus-antibody complex vaccine can improve vaccine performance.

We present efficacy of preliminary and primary vaccine trials utilizing antibody-virus complex (Ab-virus) vaccines in prevention of homologous and heterologous PRRSv infection through assessment of viral loads as determined by real-time polymerase chain reaction and PRRSv associated pathology in the lung. Additionally, we determined the safety and immunogenicity of the Ab-virus complex. Antibody-virus complex vaccines were compared to autogenous and commercially available PRRSv vaccines. An initial study utilizing Ab-virus complex vaccine and heterologous challenge, Ab-virus vaccinees developed Nab towards the vaccine and challenge strains earlier than controls and had reduced pulmonary pathology.

The primary vaccine trial demonstrated that a single Ab-virus complex vaccination was effective in preventing heterologous infection in thirty-three percent of vaccinees compared to only ten percent of pigs receiving autogenous vaccine. Vaccines did not make pigs ill. Ab-virus complex vaccinees not protected from infection following heterologous challenge, had marked reduction in viremia as compared to autogenous and unvaccinated controls. Vaccinees that became infected, had significant reduction in pulmonary viral loads which was reflective of reduced pulmonary pathology. Future studies building on this research involve determination of the breadth of cross-protection afforded with these novel vaccines and the mechanism of immune refocusing.