A protective bivalent vaccine against Rift Valley fever and bluetongue

Abstract

Rift Valley fever (RVF) and bluetongue (BT) are two important ruminant diseases transmitted by arthropods. Both viruses have shown important geographic spread leading to endemicity of BT virus (BTV) in Africa and Europe. In this work, we report a dual vaccine that simultaneously induces protective immune responses against BTV and RVFV based on modified vaccinia Ankara virus (MVA) expressing BTV proteins VP2, NS1, or a truncated form of NS1 (NS1-Nt), and RVFV Gn and Gc glycoproteins. IFNAR (−/−) mice immunized with two doses of MVA-GnGc-VP2 developed a significant neutralizing antibody response against BTV-4 and RVFV. Furthermore, the homologous prime-boost immunization with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt triggered neutralizing antibodies against RVFV and NS1-specific cytotoxic CD8+ T cells in mice. Moreover, all mice immunized with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt remained healthy after lethal challenge with RVFV or BTV-4. The homologous prime-boost vaccination with MVA-GnGc-NS1, which was the best immunization strategy observed in mice, was assayed in sheep. Clinical signs and viremia were absent or highly reduced in vaccinated sheep after challenge with BTV-4 or RVFV. These results indicate that MVA-GnGc-NS1 vaccination elicits immune protection against RVFV and BTV in sheep.

Transboundary Animal Diseases, an Overview of 17 Diseases with Potential for Global Spread and Serious Consequences

“…Formalin inactivated vaccines have also been produced but are either not as efficacious or requires boosters to maintain protection [548,549]. Further vaccine strategies have been developed, including vaccines designed to protect against other diseases as well [550], but also include drawbacks, thus necessitating continued work and continued vigilance [541]. Research is ongoing into effective antivirals, especially given the burden of human morbidity and mortality in large outbreaks [547].…”

Vaccination as a Strategy to Prevent Bluetongue Virus Vertical Transmission

“…Several platforms have been employed to induce immunity to BTV in the natural host. These include, among others, poxviruses [128][129][130], adenoviruses [130][131][132], Rift Valley fever virus (RVFV) [133,134], or herpesviruses [135,136]. These recombinant constructs were able to induce immunity to BTV in murine models and/or in the natural host, and protection was also demonstrated in some studies in the natural host [129][130][131]133,134].…”

“…These include, among others, poxviruses [128][129][130], adenoviruses [130][131][132], Rift Valley fever virus (RVFV) [133,134], or herpesviruses [135,136]. These recombinant constructs were able to induce immunity to BTV in murine models and/or in the natural host, and protection was also demonstrated in some studies in the natural host [129][130][131]133,134]. It should be noted that most protection studies with viral vectors in ruminants only detected partial protection, as in most cases, in spite of the absence of clinical signs, some level of viral replication could be detected by PCR.…”

Viral Vector Vaccines against Bluetongue Virus

“…Dual MVAs were generated in this study, cloning the GnGc gene of RVFV and the segments that encode VP2, NS1, and NS1-Nt from BTV in the F13L and TK loci, respectively, and under the control of VV early/late promoters. After a BTV challenge, all the immunized groups of IFNAR(−/−) mice showed protection, especially those immunized with NS1 and NS1-Nt, where 100% sterile protection was observed [ 44 ].…”

“…The dual MVA-GnGc-NS1 previously mentioned was tested against BTV-4 in sheep, using two doses of 10 8 PFU per animal and observing very similar results in terms of rectal temperature and viremia. Additionally, vaccinated sheep were aviremic for an RVFV challenge (except one animal at day 3 postinfection), maintaining stable biochemical parameters (aspartate transaminase, gamma-glutamyltransferase, lactate dehydrogenase, and albumin), and had mild histological lesions compared with the nonvaccinated group, which indicated the bivalent character of the designed vaccine [ 44 ]. A similar trend was observed when MVA-NS1 was used as a booster of ChAdOx1-NS1 in a heterologous prime-boost immunization, as immunized sheep showed reduced levels of viremia and lower temperatures than the control group [ 43 ].…”