Scalable live-attenuated SARS-CoV-2 vaccine candidate demonstrates preclinical safety and efficacy

Abstract

Successfully combating the COVID-19 pandemic depends on mass vaccination with suitable vaccines to achieve herd immunity. Here, we describe COVI-VAC, the only live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine currently in clinical development. COVI-VAC was developed by recoding a segment of the viral spike protein with synonymous suboptimal codon pairs (codon-pair deoptimization), thereby introducing 283 silent (point) mutations. In addition, the furin cleavage site within the spike protein was deleted from the viral genome for added safety of the vaccine strain. Except for the furin cleavage site deletion, the COVI-VAC and parental SARS-CoV-2 amino acid sequences are identical, ensuring that all viral proteins can engage with the host immune system of vaccine recipients. COVI-VAC was temperature sensitive in vitro yet grew robustly (>107 plaque forming units/mL) at the permissive temperature. Tissue viral loads were consistently lower, lung pathology milder, and weight loss reduced in Syrian golden hamsters (Mesocricetus auratus) vaccinated intranasally with COVI-VAC compared to those inoculated with wild-type (WT) virus. COVI-VAC inoculation generated spike IgG antibody levels and plaque reduction neutralization titers similar to those in hamsters inoculated with WT virus. Upon challenge with WT virus, COVI-VAC vaccination reduced lung challenge viral titers, resulted in undetectable virus in the brain, and protected hamsters from almost all SARS-CoV-2–associated weight loss. Highly attenuated COVI-VAC is protective at a single intranasal dose in a relevant in vivo model. This, coupled with its large-scale manufacturing potential, supports its potential use in mass vaccination programs.

Natural and Experimental SARS-CoV-2 Infection in Domestic and Wild Animals

“…Hamsters, particularly Syrian golden hamsters, are the most promising pre-clinical model of SARS-CoV-2 due to their consistent clinical signs and ability to transmit the virus to other hamsters, combined with their relative ease of housing and handling in biocontainment facilities. Syrian golden hamsters have already been used extensively to gain insights into the basic science of SARS-CoV-2 pathogenesis [ 156 , 157 , 158 , 159 , 160 , 161 ] and to test therapeutic interventions [ 162 , 163 , 164 , 165 , 166 , 167 ] and vaccines [ 168 , 169 , 170 , 171 , 172 ]. Moreover, there is clear evidence that older Syrian golden hamsters and Roborovski hamsters develop respiratory disease and lung pathology that recapitulates the severe disease found in older COVID-19 patients, and therefore could be highly informative models [ 77 , 81 ].…”

Should the world collaborate imminently to develop neglected live‐attenuated vaccines for COVID‐19?

“…9 ). 14 History has demonstrated that all types of vaccines can be safe or dangerous and that strict animal experiments and clinical trials can differentiate between safe vaccines and dangerous vaccines. 9 For example, clinical trials revealed the severe ADE effect of the inactivated vaccine FI-RSV for respiratory syncytial virus and the adenovirus vector vaccine for human immunodeficiency virus.…”

Can the Nasal Cavity Help Tackle COVID-19?

“…Furthermore, immunosorbent assay (ELISA) was carried out to measure IgG titers against SARS-CoV-2 spike S1 in hamsters inoculated with WT WA1 or COVI-VAC. A strong anti-spike S1 antibody response was induced, and high levels of neutralizing antibodies were determined in COVI-VAC-inoculated hamsters [67]. In December 2020 a Phase I clinical trial of COVI-VAC was commenced by Codagenix and the Serum Institute of India.…”