Use of B7 costimulatory molecules as adjuvants in a prime-boost vaccination against Visna/Maedi ovine lentivirus

Abstract

RNA transcripts of the B7 family molecule (CD80) are diminished in blood leukocytes from animals clinically affected with Visna/Maedi virus (VMV) infection. This work investigates whether the use of B7 genes enhances immune responses and protection in immunization--challenge approaches. Sheep were primed by particle--mediated epidermal bombardment with VMV gag and env gene recombinant plasmids together with plasmids encoding both CD80 and CD86 or CD80 alone, boosted with gag and env gene recombinant modified vaccinia Ankara virus and challenged intratracheally with VMV. Immunization in the presence of one or both of the B7 genes resulted in CD4+ T cell activation and antibody production (before and after challenge, respectively), but only immunization with CD80 and CD86 genes together, and not CD80 alone, resulted in a reduced number of infected animals and increased early transient cytotoxic T lymphocytes (CTL) responses. Post--mortem analysis showed an immune activation of lymphoid tissue in challenge--target organs in those animals that had received B7 genes compared to unvaccinated animals. Thus, the inclusion of B7 genes helped to enhance early cellular responses and protection (diminished proportion of infected animals) against VMV infection.

Technologies for enhanced efficacy of DNA vaccines

“…In another study, co-delivery of CD80 with HSV increased the T-cell response and protection from HSV challenge when injected intradermally but not intramuscularly, suggesting the route of immunization is important [148]. Co-delivery of CD80 ± CD86 in a prime-boost approach targeting Visna/Maevi virus resulted in CD4 + T-cell activation and reduced infection [150]. CD86 was successfully used as an adjuvant for a therapeutic vaccine against rheumatoid arthritis [151].…”

Immunization against Small Ruminant Lentiviruses

“…Immune responses were similar in potency and quality in gag plus env -immunized groups, but inclusion of both B7 molecules (CD80 and CD86) empowered antibody production and anticipated CTL responses. Most importantly, the challenge virus was only detectable by sensitive PCR in half of the immunized animals that received both B7 molecules, it being the first study showing infection clearance [55]. However, as highlighted before in plasmid immunization and, also, in vaccination studies with attenuated viruses, the pathology score was, again, increased in the most reactive groups, even those showing no detectable virus.…”

Etiology, Epizootiology and Control of Maedi-Visna in Dairy Sheep: A Review

“…There is neither a treatment nor an effective vaccine against MV. In the past, there have been attempts for the development of attenuated and subunit vaccines but none of them proved to be effective in preventing viral infections [83][84][85][86][87][88][89]. The major obstacles for the development of an effective MV vaccine include the necessity for the induction of high antibody titers against the virus, the wide genetic variation of viral strains and its continuous mutations, the increased post-infection immunological reaction, the post-vaccination challenge on the immune system and the evidence that the production of SRLV-specific neutralizing antibodies, following vaccination with whole virus-, protein-, and live attenuated-vaccines, is not always protective and in some cases may favor persistent infection [3,54].…”