Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes Virus

Abstract

Andes virus (ANDV) is a highly pathogenic South American hantavirus that causes hantavirus pulmonary syndrome (HPS).A high case fatality rate, the potential for human-to-human transmission, the capacity to infect via aerosolization, and the absence of effective therapies make it imperative that a safe, fast-acting, and effective ANDV vaccine be developed. We generated and characterized a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV surface glycoprotein precursor (VSV⌬G/ANDVGPC) as a possible vaccine candidate and tested its efficacy in the only lethal-disease animal model of HPS. Syrian hamsters immunized with a single injection of VSV⌬G/ANDVGPC were fully protected against disease when challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ depending on when the immunization occurs. At 28 days postimmunization, a lack of detectable ANDV RNA in lung, liver, and blood tissue samples, as well as a lack of seroconversion to the ANDV nucleocapsidprotein in nearly all animals, suggested largely sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV G N /G C antibodies, which seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism. Overall, our data suggest the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/postexposure treatment against lethal hantavirus infections.

Antibodies are necessary for rVSV/ZEBOV-GP–mediated protection against lethal Ebola virus challenge in nonhuman primates

“…The difference in mechanisms of protection between rAd5 and rVSV could be mediated by differences in the type of vaccineinduced immune responses generated by these two vectors. Indeed, previous studies in a hamster model of Andes virus infection have shown that, whereas rAd5 engendered a robust cytotoxic T-cell response and a short-lived antibody response (32), the rVSV vaccine generated a potent neutralizing antibody response (33). Despite these differences, both vectors protected animals from lethal Andes virus challenge.…”

The vesicular stomatitis virus-based Ebola virus vaccine: From concept to clinical trials

“…27 , 49 , 50 In addition, a dual VSV-based vector expressing the GPs of viruses from two different virus families was shown to protect against both viruses in an animal model with similar short time to protection and post-exposure efficacy as VSV-EBOV. 18 , 51 Now that the safety, efficacy, and feasibility of the VSV platform have been proven, it is time to finally license this platform, as has been recently done in Russia. In addition, moving VSV-based vaccines for other pathogenic viruses with outbreak potential, such as MARV, LASV, and Nipah virus, forward to clinical trials should be a priority.…”

Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

“…Using synthetic biology, it would be possible to produce DNA vaccine plasmids against all of the known pathogenic strains of hantaviruses; however, from a vaccine development perspective, this would be expensive, impractical, and unnecessary. We and others have demonstrated that neutralizing antibodies are sufficient to protect against infection and/or disease (14,15,31,37,38). Thus, the production of cross-neutralizing antibodies is a reasonable predictor that the vaccine will be cross-protective.…”

“…When Syrian hamsters are exposed to ANDV, they develop a lethal disease that closely resembles HPS in humans (14,23,(31)(32)(33)(34)(35)(36). Recombinant adenovirus and vesicular stomatitis virus vectors encoding ANDV N or glycoproteins have been shown to protect against lethal HPS in the hamster model (34,37). In an earlier study, we found that the HTNV M gene-based DNA vaccine conferred partial but not statistically significant protection against an i.m.…”