A SARS-CoV-2 recombinant spike protein vaccine (S-268019-b) for COVID-19 prevention during the Omicron-dominant period: A phase 3, randomised, placebo-controlled clinical trial.

Clinical trials of new vaccines based on existing variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are often impacted by the emergence of new virus variants. We evaluated the efficacy, immunogenicity, and safety of S-268019-b, a recombinant spike protein subunit vaccine based on the ancestral strain, for preventing symptomatic coronavirus disease 2019 (COVID-19) during the Omicron (BA.2)-dominant period in Vietnam. In this multicentre, phase 3, randomised (2:1), observer-blind, placebo-controlled crossover study, participants received 2 intramuscular doses (28 days apart) of either 10 µg of S-268019-b (Recombinant S-protein vaccine) or placebo. The primary endpoint was incidence of laboratory-confirmed symptomatic COVID-19 before crossover, with onset within 14 days following the second dose, in participants who were seronegative and reverse transcription polymerase chain reaction (RT-PCR)-negative at baseline. The secondary endpoints included immunogenicity and safety. In total, 8,594 participants were randomised (S-268019-b [n = 5,727]; placebo [n = 2,867]). Vaccine efficacy versus placebo was 39·1 % (95 % confidence interval [CI]:26·6-49·5; one-sided P = 0·0723). The incidence rate (95 % CI) of symptomatic COVID-19 was 776·41/1,000 person-years (682·04-880·19) in the S-268019-b group and 1272·87/1,000 person-years (1101·32-1463·57) in the placebo group. The geometric mean titres (95 % CI) of the SARS-CoV-2 neutralising antibody increased on Day 57 versus baseline with S-268019-b (34·66 [27·04-44·41] versus 2·50 (non-estimable) but not with placebo. There were no safety concerns regarding S-268019-b. S-268019-b did not demonstrate the targeted efficacy threshold against symptomatic COVID-19; however, findings were comparable with other prophylactic vaccines based on ancestor strain during the Omicron-dominant period. S-268019-b demonstrated immunogenicity and was well-tolerated. ClinicalTrials.gov identifier: NCT05212948.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vu Dinh Thiem reports financial support was provided by Shionogi & Co., Ltd. Andrew J Pollard reports financial support was provided by Gates Foundation, Wellcome Trust, Cepi, MRC, NIHR, Serum Institute of India, Astra Zeneca, and EC. Andrew J. Pollard reports financial support was provided by Shionogi and Co Ltd. Akari Kamitani reports a relationship with Shionogi and Co Ltd that includes: employment. Yukio Tada reports a relationship with Shionogi and Co Ltd that includes: employment and equity or stocks. Hidenori Fukuyama reports a relationship with Shionogi and Co Ltd that includes: employment. Yuka Iwasaki reports a relationship with Shionogi and Co Ltd that includes: employment. Mari Ariyasu reports a relationship with Shionogi and Co Ltd that includes: employment. Takuhiro Sonoyama reports a relationship with Shionogi and Co Ltd that includes: employment and equity or stocks. Andrew J Pollard is a contributor to intellectual property licensed by Oxford University Innovation to AstraZeneca and was honorary Chair of DHSC’s Joint Committee on Vaccination and Immunisation and member of WHO’s SAGE until 2022. Pham Thi Van Anh, Chu Van Men, and Do Thai Hung have no conflicts to declare. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.