Comparative efficacy of two next-generation Rift Valley fever vaccines
Kortekaas, J.A. ; Oreshkova, N. ; Keulen, L.J.M. van; Kant, J. ; Bosch, B.J. ; Bouloy, M. ; Moulin, V. ; Goovaerts, D. ; Moormann, R.J.M. - \ 2014
Vaccine 32 (2014). - ISSN 0264-410X - p. 4901 - 4908.
nss protein - down-regulation - mp-12 vaccine - virus-vaccine - safety - transcription - sheep - immunogenicity - attenuation - rna
Rift Valley fever virus (RVFV) is a re-emerging zoonotic bunyavirus of the genus Phlebovirus. A natural isolate containing a large attenuating deletion in the small (S) genome segment previously yielded a highly effective vaccine virus, named Clone 13. The deletion in the S segment abrogates expression of the NSs protein, which is the major virulence factor of the virus. To develop a vaccine of even higher safety, a virus named R566 was created by natural laboratory reassortment. The R566 virus combines the S segment of the Clone 13 virus with additional attenuating mutations on the other two genome segments M and L, derived from the previously created MP-12 vaccine virus. To achieve the same objective, a nonspreading RVFV (NSR-Gn) was created by reverse-genetics, which not only lacks the NSs gene but also the complete M genome segment. We have now compared the vaccine efficacies of these two next-generation vaccines and included the Clone 13 vaccine as a control for optimal efficacy. Groups of eight lambs were vaccinated once and challenged three weeks later. All mock-vaccinated lambs developed high fever and viremia and three lambs did not survive the infection. As expected, lambs vaccinated with Clone 13 were protected from viremia and clinical signs. Two lambs vaccinated with R566 developed mild fever after challenge infection, which was associated with low levels of viral RNA in the blood, whereas vaccination with the NSR-Gn vaccine completely prevented viremia and clinical signs.
One health approach to Rift Valley fever vaccine development
Kortekaas, J.A. - \ 2014
Antiviral Research 106 (2014)24. - ISSN 0166-3542 - p. 24 - 32.
lethal virus challenge - saudi-arabia - immune-responses - rhesus macaques - mp-12 vaccine - south-africa - enzootic hepatitis - northeastern kenya - ifnar(-/-) mice - rvfv infection
Since its discovery in the 1930s, Rift Valley fever virus (RVFV) spread across the African continent and invaded the Arabian Peninsula and several islands off the coast of Southeast Africa. The virus causes recurrent outbreaks in these regions, and its continued spread is of global concern. Next-generation veterinary vaccines of improved efficacy and safety are being developed that can soon be used for the widespread vaccination of livestock. However, due to regulatory and economic challenges, vaccine manufacturers have been reluctant to develop a human vaccine. Recent innovations in veterinary vaccinology, animal models and licensing strategies can now be used to overcome these hurdles. This paper reviews the historical impact of RVFV on human health and proposes strategies to develop and license a next-generation vaccine for both animals and humans
A Single Vaccination with an Improved Nonspreading Rift Valley Fever Virus Vaccine Provides Sterile Immunity in Lambs
Oreshkova, N.D. ; Keulen, L.J.M. van; Kant, J. ; Moormann, R.J.M. ; Kortekaas, J.A. - \ 2013
PLoS ONE 8 (2013)10. - ISSN 1932-6203 - 10 p.
nss protein - mp-12 vaccine - sheep - safety - efficacy - cattle - immunogenicity - expression - protection - challenge
Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 106.3 TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine.