Inactivated rabies virus vectored SARS-CoV-2 vaccine prevents disease in a Syrian hamster model

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from weight loss and viral replication in the lungs and nasal turbinates three days after challenge with SARS-CoV-2. CORAVAX also prevented lung disease, as indicated by the significant reduction in lung pathology. This study highlights CORAVAX as a safe, immunogenic, and efficacious vaccine that warrants further assessment in human trials.

Cellular tropism of SARS-CoV-2 in the respiratory tract of Syrian hamsters and B6.Cg-Tg(K18-ACE2)2Prlmn/J transgenic mice

“…Infected hamsters had a high viral load in the upper respiratory tract but also developed more lower respiratory disease than standard laboratory mice, and they support efficient transmission of SARS-CoV-2, are easier to handle than ferrets (which do not develop moderate respiratory disease and less susceptible in transmission studies), and are considerably less expensive with fewer ethical concerns than nonhuman primates. 9 , 10 , 13 , 14 , 17 , 20 , 28 , 33 , 40 , 43 , 53 Recent publications used hamster models for SARS-CoV-2 vaccine development, and these have included the use of a number of backbones or vectors, including rabies, 22 measles, 25 Newcastle disease, 48 yellow fever, 42 monoclonal antibodies, 2 , 23 , 24 , 44 and nanobodies. 29 , 51 The hamster model has also been used to study new therapeutic agents for the prevention and treatment of infection including favipiravir, 21 hydroxychloroquine, 41 methylprednisone, 52 plant extracts, 34 interferon, 16 remdesivir, 52 anti-leprosy medications, 54 and ranitidiine bismuth citrate.…”

Inactivated Rabies Virus Vectored MERS-Coronavirus Vaccine Induces Protective Immunity in Mice, Camels, and Alpacas

“…In recent years, the rabies virus has been successfully used as a vaccine vector for many zoonotic diseases, including Ebola virus (EBOV) disease and COVID-19. Compared with another viral vector, the rabies vaccine vector has an excellent safety profile and impressive immunogenicity profiles in animals and humans (24)(25)(26)(27)(28). Previous studies by us and other research groups have demonstrated that the rabies vector could be desirable for the development of the MERS vaccine.…”

“…When rescuing recombinant virus based on RABV vector, the length and form of foreign antigen expression frame as well as its location in the RABV genome would be considered, as these factors have an effect on the expression of target antigen protein and the efficiency of rescued recombinant virus and its virus titer (34). Several studies have demonstrated that the length of inserted exogenous expression frame within 2,000 bp would be ideal (24)(25)(26)(27)(28)(29). Besides, of the two subunits of MERS-CoV spike protein, S1 is the one that contains the RBD and the N-terminal, which are the regions against which more neutralizing antibodies are generated (52).…”

“…Rabies virus has been proven to be a favorable vaccine vector and has been widely used to develop recombinant bivalent vaccines. Compared with live viral vectorbased vaccines, inactivated recombinant rabies virus-vectored vaccines lessen the concerns of safety and production scalability (23)(24)(25)(26)(27)(28)(29). Based on our previous study, the S1 subunit of MERS-CoV spike protein is an effective target able to elicit antigenspecific humoral and cellular immune responses (30).…”

COVID-19 Animal Models and Vaccines: Current Landscape and Future Prospects

“…Vaccinated hamsters showed a reduced or disappeared infectious virus in the lungs and less body weight loss, as well as less histopathological changes of pneumonia. They produced a level of NAbs against SARS-CoV-2 [24][25][26][27]. In short, golden hamsters reflect certain clinical manifestations and immune responses after the administration of COVID-19 vaccines.…”