Lead SARS-CoV-2 Candidate Vaccines: Expectations from Phase III Trials and Recommendations Post-Vaccine Approval

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily through respiratory droplets/aerosols and it causes COVID-19. The virus infects epithelial cells by using the spike protein on its surface to bind to angiotensin-converting enzyme 2 receptor on the cells. Thus, candidate vaccines targeting the spike protein are currently being developed to prevent against infections. Approximately 44 SARS-CoV-2 candidate vaccines are in clinical trials (phase I-III) and an additional 164 candidates are in preclinical stages. The efficacy data from phase I/II trials of lead candidate vaccines look very promising with virus-neutralizing geometric mean antibody titers in the range of 16.6-3906. Most recently, two SARS-CoV-2 candidate vaccines, BNT162b2 and mRNA-1273, have been granted the first emergency use authorization (EUA) in the U.S.; BNT162b2 has also been granted an EUA in the United Kingdom, Canada, and in the European Union. This review assesses whether SARS-CoV-2 candidate vaccines (with approved EUA or in phase III trials) meet the criteria for an ideal SARS-CoV-2 vaccine. The review concludes with expectations from phase III trials and recommendations for phase IV studies (post-vaccine approval).

Keywords: COVID-19; SARS-CoV-2; SARS-CoV-2 vaccines; clinical trials.

Figure 1

NGMATs of SARS-CoV-2 candidate vaccines in phase III trials. (A) NGMATs of CoronaVac, inactivated SARS-CoV-2, Ad5 nCoV, Sputnik V, ChAdOx1 nCoV-19, Ad26.COV2.S, mRNA-1273, and BNT162b2. (B) NGMATs of NVX-CoV2373. Neutralization assays were performed using wild-type virus except with the BNT162b2 vaccine (* a reporter SARS-CoV-2 virus expressing mNeonGreen was used). Tissue culture infectious dose (TCID).