Abstract
BackgroundRift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.MethodsHere, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.ResultsA single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.ConclusionsTogether the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.
Highlights
Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have occurred in the Arabian Peninsula
Induction of RVF virus neutralizing antibodies and efficacy against RVF virus challenge We first compared RVF virus neutralizing antibody titers between vaccination regimens, measured in sera sampled eight weeks post-vaccination. Both vaccines elicited RVF virus neutralizing antibodies, though, in the absence of adjuvants, mice receiving human adenovirus type 5 (HAdV5)-GnGc mounted higher virus neutralizing titers than those vaccinated with ChAdOx1-GnGc (Mann–Whitney U test p = 0.004; Figure 1). This difference in immunogenicity was no longer evident when comparisons were made between the HAdV5-GnGc group and the groups receiving ChAdOx1-GnGc in co-administration with either MatrixMTM or AddaVaxTM adjuvant (Kruskal-Wallis test p = 0.6)
Both Matrix-MTM and AddaVaxTM adjuvant significantly enhanced the RVF virus neutralizing response induced by ChAdOx1-GnGc, but the slight increase in HAdV5-GnGc immunogenicity by either adjuvant did not reach statistical significance (Figure 1)
Summary
Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have occurred in the Arabian Peninsula. Rift valley fever (RVF) is one of numerous zoonotic diseases affecting human and livestock health in Africa, and has previously spread to the Arabian Peninsula [1,2]. Humans and animals recovering from infection with RVF virus develop long-lasting immunity that is attributable to the acquisition of virus-neutralizing antibodies [3,5,6,7,8]. Development of Gn and Gc-based vaccines utilizing vectors with an established human safety profile could be a promising strategy for a future human RVF vaccine
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