PMID- 37731938 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230922 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 64 DP - 2023 Oct TI - Safety and immunogenicity of multivalent SARS-CoV-2 protein vaccines: a randomized phase 3 trial. PG - 102195 LID - 10.1016/j.eclinm.2023.102195 [doi] LID - 102195 AB - BACKGROUND: COVID-19 vaccines that offer broad-spectrum protection are needed. We aimed to evaluate the safety and immunogenicity of multivalent vaccines, SCTV01E and SCTV01C, and compare them with an inactivated vaccine. METHODS: In the phase 3 trial (ClinicalTrials.gov: NCT05323461), adult participants previously vaccinated with Sinopharm's inactivated SARS-CoV-2 vaccine (BBBIP-CorV) were assigned to receive one booster dose of BBBIP-CorV, 20 mug SCTV01C, or 30 mug SCTV01E. The primary endpoint was to evaluate the geometric mean titers (GMT) of neutralizing antibody (nAb) against the Delta and Omicron BA.1 variants on day 28 after injection. Additional endpoints included GMTs of nAb against Delta (B.1.617.2) and Omicron BA.1 variants on day 180, GMTs against BA.5 on day 28, as well as solicited adverse events (AEs) within seven days, unsolicited AEs within 28 days, and serious AEs, AEs of special interest within 180 days after vaccination. FINDINGS: Between May 30, 2022 and October 28, 2022, a total of 1351 participants were randomized to BBBIP-CorV, SCTV01C, or SCTV01E in a 1:1:1 ratio, with immunogenicity assessments performed on the first 300 participants. For BBBIP-CorV, SCTV01C, and SCTV01E groups, the day 28 GMTs of neutralizing antibody against Omicron BA.1 were a 2.38-, 19.37-, and 28.06-fold increase from baseline; the GMTs against Omicron BA.5 were 2.07-, 15.89- and 21.11-fold increases; the GMTs against Delta variants were 1.97-, 12.76-, and 15.88-fold increases, respectively. The day 28 geometric mean ratio (GMR) of SCTV01C/BBIBP-CorV for Omicron BA.1 was 6.49 (95% CI: 4.75, 8.88), while the GMR of SCTV01E/BBIBP-CorV was 9.56 (95% CI: 6.85, 13.33). For the Delta variant, the day 28 GMR of SCTV01C/BBIBP-CorV was 6.26 (95% CI: 4.78, 8.19), and the day 28 GMR of SCTV01E/BBIBP-CorV was 7.26 (95% CI: 5.51, 9.56). On Day 180, the GMTs against Omicron BA.1 were 2.80-, 9.51-, and 15.56-fold increase from baseline, while those against Delta were 1.58-, 5.49-, and 6.63-fold for BBBIP-CorV, SCTV01C, and SCTV01E groups, respectively. Subgroup analyses showed that SCTV01C and SCTV01E induced uniformly high GMTs against both BA.1 and BA.5, demonstrating its superiority over BBIBP-CorV, regardless of baseline GMT levels. Safety and reactogenicity were similar among the three vaccines. Most AEs were Grade 1 or 2. There were 15 >/=Grade 3 AEs: 6 in the BBIBP-CorV group, 4 in the SCTV01C group and 5 in the SCTV01E group. No SAE was reported and one grade 1 AESI (Bell's palsy) was observed in SCTV01C group. INTERPRETATION: A booster dose of the tetravalent vaccine SCTV01E consistently induced high neutralizing antibody responses against Omicron BA.1, BA.5, and Delta variants, demonstrating superiority over inactivated vaccine. There is evidence to suggest that SCTV01E may have GMT superiority over bivalent vaccine SCTV01C against Delta, BA.1 and BA.5 variants. FUNDING: This study was sponsored by Sinocelltech Ltd., and funded by the Beijing Science and Technology Planning Project [Z221100007922012] and the National Key Research and Development Program of China [2022YFC0870600]. CI - (c) 2023 The Authors. FAU - Hannawi, Suad AU - Hannawi S AD - Internal Medicine Department, Al Kuwait-Dubai (ALBaraha) Hospital, Dubai, United Arab Emirates. FAU - Yan, Lixin AU - Yan L AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. FAU - Saifeldin, Linda AU - Saifeldin L AD - General Surgery Department, Al Kuwait-Dubai (ALBaraha) Hospital, Dubai, United Arab Emirates. FAU - Abuquta, Alaa AU - Abuquta A AD - Internal Medicine Department, Al Kuwait-Dubai (ALBaraha) Hospital, Dubai, United Arab Emirates. FAU - Alamadi, Ahmad AU - Alamadi A AD - Ear, Nose and Throat Department (ENT), Al Kuwait-Dubai (ALBaraha) Hospital, Dubai, United Arab Emirates. FAU - Mahmoud, Sally A AU - Mahmoud SA AD - Biogenix Labs, G42 Healthcare, Dubai, United Arab Emirates. FAU - Hassan, Aala AU - Hassan A AD - Internal Medicine Department, Al Kuwait-Dubai (ALBaraha) Hospital, Dubai, United Arab Emirates. FAU - Zhang, Miaomiao AU - Zhang M AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. FAU - Gao, Cuige AU - Gao C AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. FAU - Chen, Yuanxin AU - Chen Y AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. FAU - Gai, Wenlin AU - Gai W AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. FAU - Xie, Liangzhi AU - Xie L AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. LA - eng SI - ClinicalTrials.gov/NCT05323461 PT - Journal Article DEP - 20230908 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC10507195 OTO - NOTNLM OT - Booster OT - Immunogenicity OT - SARS-CoV-2 OT - Safety OT - Tetravalent vaccine COIS- Lixin Yan, Cuige Gao, Miaomiao Zhang, Yuanxin Chen and Wenlin Gai are employees of Sinocelltech Ltd., and Liangzhi Xie has potential stock option interests in the company. All authors declare no other conflicts of interest. EDAT- 2023/09/21 06:42 MHDA- 2023/09/21 06:43 PMCR- 2023/09/08 CRDT- 2023/09/21 04:07 PHST- 2023/05/11 00:00 [received] PHST- 2023/08/11 00:00 [revised] PHST- 2023/08/16 00:00 [accepted] PHST- 2023/09/21 06:43 [medline] PHST- 2023/09/21 06:42 [pubmed] PHST- 2023/09/21 04:07 [entrez] PHST- 2023/09/08 00:00 [pmc-release] AID - S2589-5370(23)00372-3 [pii] AID - 102195 [pii] AID - 10.1016/j.eclinm.2023.102195 [doi] PST - epublish SO - EClinicalMedicine. 2023 Sep 8;64:102195. doi: 10.1016/j.eclinm.2023.102195. eCollection 2023 Oct.