Abstract

Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Given the concerns these findings raised, and the close contact between humans and cats, we aimed to develop a vaccine candidate that could reduce SARS-CoV-2 infection and in addition to prevent spread among cats. Here we report that a Replicon Particle (RP) vaccine based on Venezuelan equine encephalitis virus, known to be safe and efficacious in a variety of animal species, could induce neutralizing antibody responses in guinea pigs and cats. The design of the SARS-CoV-2 spike immunogen was critical in developing a strong neutralizing antibody response. Vaccination of cats was able to induce high neutralizing antibody responses, effective also against the SARS-CoV-2 B.1.1.7 variant. Interestingly, in contrast to control animals, the infectious virus could not be detected in oropharyngeal or nasal swabs of vaccinated cats after SARS-CoV-2 challenge. Correspondingly, the challenged control cats spread the virus to in-contact cats whereas the vaccinated cats did not transmit the virus. The results show that the RP vaccine induces protective immunity preventing SARS-CoV-2 infection and transmission. These data suggest that this RP vaccine could be a multi-species vaccine useful to prevent infection and spread to and between animals should that approach be required.

Highlights

  • SARS-CoV-2 is an extremely contagious respiratory coronavirus that emerged in China in late 2019 and has since spread globally causing the on-going coronavirus disease 2019 (COVID-19) pandemic

  • Animals were immunized with 1 × 107 Venezuelan equine encephalitis virus (VEEV) replicon particles (RP) via the intramuscular route at day 0, 21, and 42 of the study, and serum for analysis was collected at day 56

  • Relative to wild type-S antigen, a trend towards higher neutralization titers were observed for sera of animals immunized with the VEEV RP vaccine producing the S antigens containing a mutated furin cleavage site (FCS), replacement of the TM/cytoplasmic tail domain (CTD) for that of vesicular stomatitis virus G protein (VSV)-G in combination with the 2P

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Summary

Introduction

SARS-CoV-2 is an extremely contagious respiratory coronavirus that emerged in China in late 2019 and has since spread globally causing the on-going coronavirus disease 2019 (COVID-19) pandemic. As ACE2 orthologs that are highly similar to the human ACE2 receptor are present on the cells of a number of other animals it is important to understand whether those potential hosts can play any role in disease spread. Since the first human infections, it has been shown that cats, dogs, ferrets, hamsters, and mink can be readily infected either in laboratory studies or via natural transmission[1,2,3,4,5] The role these susceptible animals play in the human epidemiology is unclear, though two-way transmission between mink and humans has been demonstrated leading to the culling of all animals in mink farms from Denmark and the Netherlands[3]. It is of utmost importance to understand the role of animals in the spread of this virus, especially with regard to their potential to act as a viral reservoir and to develop important viral variants which thereby influence the overall epidemiology

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