Cross-reactive immunity to porcine reproductive and respiratory syndrome virus and its contribution to protection

Due to the vast geographical distribution and significant economic losses generated, porcine reproductive and respiratory syndrome virus (PRRSV) can be considered the most important swine pathogen of contemporary times. Current control and eradication strategies against PRRSV have difficulty succeeding because of their complex nature and the absence of an effective vaccine. A major obstacle for PRRSV vaccine development is the broad heterogeneity of the virus, both at the genetic and antigenic level, its rapid evolution, and an incomplete knowledge of the immune responses responsible for clearing the virus from the host. Specifically, how known correlates of protection against PRRSV—neutralizing antibodies and T cells—cross-react with heterologous isolates and mediate cross-protection is inadequately understood. The objectives of this dissertation were (i) to determine the extent of cross-reactivity of immune responses against PRRSV, and (ii) to ascertain how cross-reactive immune responses mediate protection against heterologous isolates. T cell responses were found to be cross-reactive among PRRSV-2 isolates, but extremely variable among individual animals, while the neutralizing antibody response induced by a single infection with PRRSV was deemed to be solely self-neutralizing. Sequential exposure to heterologous PRRSV-2 isolates elicited neutralizing antibodies to the isolates used for infection and challenge, as well as other heterologous PRRSV-2 isolates. Furthermore, prior exposure to PRRSV afforded cross-protection against heterologous challenge, with reduction in viremia, tissue viral load and the extent of microscopic lung lesions; however, protection was still suboptimal. T cell cross-reactivity between PRRSV-1 and PRRSV-2 was evaluated at the structural protein level and was deemed to be feeble or absent. Prior exposure to PRRSV-1 did not prime the T cell response against the PRRSV-2 structural proteins after PRRSV-2 challenge. Collectively, the results in this dissertation contribute to furthering the understanding of immune responses against PRRSV and may be used in the development of a better vaccine. Advisor: Fernando A. Osorio