Safety and immunogenicity of four-segmented Rift Valley fever virus in the common marmoset.

Autor: Wichgers Schreur PJ; Department of Virology and Molecular Biology, Wageningen Bioveterinary Research, Wageningen University & Research, Lelystad, The Netherlands. paul.wichgersschreur@wur.nl.; BunyaVax B.V., Lelystad, The Netherlands. paul.wichgersschreur@wur.nl., Mooij P; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Koopman G; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Verstrepen BE; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Fagrouch Z; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Mortier D; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., van Driel N; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Kant J; Department of Virology and Molecular Biology, Wageningen Bioveterinary Research, Wageningen University & Research, Lelystad, The Netherlands., van de Water S; Department of Virology and Molecular Biology, Wageningen Bioveterinary Research, Wageningen University & Research, Lelystad, The Netherlands., Bogers WM; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Punt C; BunyaVax B.V., Lelystad, The Netherlands., van Keulen L; Department of Virology and Molecular Biology, Wageningen Bioveterinary Research, Wageningen University & Research, Lelystad, The Netherlands., Verschoor EJ; Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands., Kortekaas J; Department of Virology and Molecular Biology, Wageningen Bioveterinary Research, Wageningen University & Research, Lelystad, The Netherlands.; Laboratory of Virology, Wageningen University & Research, Wageningen, The Netherlands.
Jazyk: angličtina
Zdroj: NPJ vaccines [NPJ Vaccines] 2022 May 18; Vol. 7 (1), pp. 54. Date of Electronic Publication: 2022 May 18.
DOI: 10.1038/s41541-022-00476-y
Abstrakt: Rift Valley fever virus (RVFV) is an emerging mosquito-borne bunyavirus that is highly pathogenic to wild and domesticated ruminants, camelids, and humans. While animals are exclusively infected via mosquito bites, humans can also be infected via contact with contaminated tissues or blood. No human vaccine is available and commercialized veterinary vaccines do not optimally combine efficacy with safety. We previously reported the development of two novel live-attenuated RVF vaccines, created by splitting the M genome segment and deleting the major virulence determinant NSs. The vaccine candidates, referred to as the veterinary vaccine vRVFV-4s and the human vaccine hRVFV-4s, were shown to induce protective immunity in multiple species after a single vaccination. Anticipating accidental exposure of humans to the veterinary vaccine and the application of hRVFV-4s to humans, the safety of each vaccine was evaluated in the most susceptible nonhuman primate model, the common marmoset (Callithrix jacchus). Marmosets were inoculated with high doses of each vaccine and were monitored for clinical signs as well as for vaccine virus dissemination, shedding, and spreading to the environment. To accurately assess the attenuation of both vaccine viruses, separate groups of marmosets were inoculated with the parent wild-type RVFV strains. Both wild-type strains induced high viremia and disseminated to primary target organs, associated with mild-to-severe morbidity. In contrast, both vaccines were well tolerated with no evidence of dissemination and shedding while inducing potent neutralizing antibody responses. The results of the studies support the unprecedented safety profile of both vaccines for animals and humans.
(© 2022. The Author(s).)
Databáze: MEDLINE
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