A Rift Valley fever virus Gn ectodomain-based DNA vaccine induces a partial protection not improved by APC targeting

Rift Valley fever virus, a phlebovirus endemic in Africa, causes serious diseases in ruminants and humans. Due to the high probability of new outbreaks and spread to other continents where competent vectors are present, vaccine development is an urgent priority as no licensed vaccines are available outside areas of endemicity. In this study, we evaluated in sheep the protective immunity induced by DNA vaccines encoding the extracellular portion of the Gn antigen which was either or not targeted to antigen-presenting cells. The DNA encoding untargeted antigen was the most potent at inducing IgG responses, although not neutralizing, and conferred a significant clinical and virological protection upon infectious challenge, superior to DNA vaccines encoding the targeted antigen. A statistical analysis of the challenge parameters supported that the anti-eGn IgG, rather than the T-cell response, was instrumental in protection. Altogether, this work shows that a DNA vaccine encoding the extracellular portion of the Gn antigen confers substantial- although incomplete -protective immunity in sheep, a natural host with high preclinical relevance, and provides some insights into key immune correlates useful for further vaccine improvements against the Rift Valley fever virus. A vaccine made from the genome of Rift Valley fever virus (RVFV) offers partial protection, but pieces of the puzzle are missing, say scientists. French and Spanish researchers, led by the French National Institute for Agricultural Research's Isabelle Schwartz-Cornil, tested in sheep three slightly-differing vaccine candidates using RVFV genes. Such DNA vaccines are designed to generate proteins which a host's immune system can use to arm itself against a genuine viral infection. Two of the candidates, designed to target cells that would present the viral proteins to the host's immune system, provided some benefit to the vaccinated sheep. However, the third untargeted candidate, was the most efficient at protecting sheep, although not completely, and at boosting antibody levels despite not neutralizing the virus. These results provide hope for DNA vaccines against RVFV, and offer direction for future research effort