Recombinant vesicular stomatitis virus vector vaccines for WHO blueprint priority pathogens

Fathi, Anahita; Dahlke, Christine; Addo, Marylyn M.

th SARS-CoV and conferred protection as measured by low or undetectable SARS-CoV viral loads in the respiratory tract, even when challenged 4 months p. v. Using antisera from VSV-S vaccinated mice in naïve mice, it could further be shown that the protective effect was mediated by antibodies. 117 This vaccine candidate was then attenuated by replacing VSV G with SARS-CoV S, resulting in VSVΔG-S. Immunogenicity of the replication-defective vector was surprisingly greater than the immunogenicity of VSV-S when applied i.m., an effect the authors argued that could be due to a higher expression of SARS-CoV S protein in VSVΔG-S, among others. In an analogous manner, VSVΔG was later used to create a MERS-CoV vaccine by expressing the MERS-CoV spike protein (S), and VSVΔG-MERS displayed immunogenicity in rhesus monkeys. 118 To date, no human clinical trials have been reported for VSV-based CoV vaccines and the WHO roadmap for MERS-CoV research and product development does not currently include rVSV-vectored vaccines in the port-folio of vectored vaccines. 119 Zika virus rVSV vectors have also been employed in designing vaccine candidates against Zika virus (ZIKV), a flavivirus closely related to Dengue, West-Nile, Japanese encephalitis and Yellow Fever viruses, which has been associated with severe neurological disorders such as microcephaly in newborns and Guillan-Barré Syndrome. In 2015-2017, the spread of ZIKV infections received attention when it rapidly disseminated from Brazil throughout the Americas, where no autochthonous case of ZIKV infection had been described before 2015. 120, 121 rVSV vaccine vector expressing diverse ZIKV antigens have been described in proof-of-concept studies. In 2017, an rVSV vectors that entails a mutated M protein as an attenuation factor (VSVm) and expresses either Zika envelope (ZENV) alone or ZENV containing the precursor to membrane (prM) proteins (ZprME) was described. The constructs remained replication competent. In mice, vaccination did not trigger any overt pathology and VSVm-ZprME vaccination did induce neutralizing antibody titers. 122 As ZIKV infection does not lead to disease in adult mice, challenge studies were performed in offspring of vaccinated mothers and, therefore, statements about the efficacy of the vaccine were limited.