CTLA4 mediated targeting enhances immunogenicity against PRRSV in a DNA prime/killed virus boost strategy

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of porcine reproductive and respiratory syndrome (PRRS), causing heavy economic losses to the swine industry all over the world. As current vaccination strategies could only confer limited and incomplete protection against PRRSV infection, a safe and efficient PRRSV vaccine is urgently needed. Vaccination with cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) and antigen fusion expression plasmid which could target antigens to antigen presenting cells (APCs) has shown promising improvement of immunogenicity to antigens. In the present study, a fusion expression plasmid of CTLA4 and PRRSV GP5 was constructed. PRRSV-specific antibodies, neutralizing antibodies (NAs), cytokines of IFNγ and IL4, and the lymphocyte proliferation activity were analyzed in mice immunized with the constructed plasmids. Immunization of mice with the CTLA4 targeted plasmid leads to a significant enhancement of humoral and cellular immune responses. Moreover, this effect could be further augmented when the mice were boosted with a killed PRRSV vaccine after DNA vaccine priming. Our data imply that both the APC-target and heterologous prime-boost strategies could be used to improve the immune efficacy of vaccines against PRRSV in pigs in the future.