PMID- 36470077 OWN - NLM STAT- MEDLINE DCOM- 20230123 LR - 20231213 IS - 2352-3964 (Electronic) IS - 2352-3964 (Linking) VI - 87 DP - 2023 Jan TI - Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C, in adults previously vaccinated with mRNA vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial. PG - 104386 LID - S2352-3964(22)00568-0 [pii] LID - 10.1016/j.ebiom.2022.104386 [doi] LID - 104386 AB - BACKGROUND: Booster vaccination is an efficient way to address the waning protection of vaccines and immune escape of SARS-CoV-2 variants. We aimed to assess the safety and immunogenicity of SCTV01C, a novel bivalent protein vaccine as a booster for people who previously received two doses of mRNA vaccine. METHODS: In this randomized, phase 1/2 trial, adults fully vaccinated with mRNA vaccines 3-24 month earlier were enrolled. Participants received SCTV01C at 20 mug, 40 mug or placebo. The primary endpoints were adverse reactions within 7 days and immunogenicity on Day 28 after vaccination. This trial was registered with ClinicalTrials.gov (NCT05043311). FINDINGS: Between January 27 and April 28, 2022, 234 adults were randomly assigned to receive SCTV01C or placebo. The most common solicited adverse events (AEs) were Grade 1 injection-site pain (10.7%) and pyrexia (6.3%). There were no reports of Grade 3 or above solicited AE, serious AEs or AEs of special interests. On Day 28 post the booster, the geometric mean concentrations (GMCs) of the specific binding IgG antibodies to spike protein for placebo, 20 mug and 40 mug SCTV01C were 1649, 4153 and 5354 BAU/mL, with fold of increase from baseline of 1.0, 2.8 and 3.4-fold, respectively. GMTs of neutralizing antibodies against live Delta variant were 1280, 3542, and 4112, with fold of increase of 1.1, 3.9 and 4.1-fold, respectively; GMTs of neutralizing antibodies against live Omicron variant were 218, 640, and 1083, with fold of increase of 1.1, 4.4 and 5.1-fold, respectively. Participants with low neutralizing antibody titers at baseline (below the lower limit of quantitation) had 64.0 and 49.4-fold of increase in GMTs for Delta and Omicron, respectively. INTERPRETATION: The heterologous booster of SCTV01C was safe, and induced uniformly high cross-neutralization antibody responses against Delta and Omicron variants. FUNDING: Beijing Science and Technology Plan Project (Z221100007922012) and the National Key Research and Development Program of China (2022YFC0870600) supported this study. CI - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved. FAU - Hannawi, Suad AU - Hannawi S AD - Internal Medicine Department, Al Kuwait-Dubai (ALBaraha) Hospital, Dubai, United Arab Emirates. 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 - Liu, Dongfang AU - Liu D AD - Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing, China. FAU - Yan, Lixin AU - Yan L 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; Cell Culture Engineering Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: LX@sinocelltech.com. LA - eng SI - ClinicalTrials.gov/NCT05043311 PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial DEP - 20221205 PL - Netherlands TA - EBioMedicine JT - EBioMedicine JID - 101647039 RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (mRNA Vaccines) RN - 0 (SCTV01C vaccine) RN - 0 (Vaccines, Combined) RN - 0 (COVID-19 Vaccines) RN - SARS-CoV-2 variants SB - IM MH - Adult MH - Humans MH - Antibodies, Neutralizing MH - Antibodies, Viral MH - *COVID-19/prevention & control MH - Double-Blind Method MH - mRNA Vaccines MH - SARS-CoV-2 MH - Vaccines, Combined MH - *COVID-19 Vaccines/adverse effects PMC - PMC9720098 OTO - NOTNLM OT - Bivalent protein vaccine OT - Booster OT - Immunogenicity OT - SARS-CoV-2 OT - SCTV01C OT - Safety COIS- Declaration of interests Dr. Liangzhi Xie, Dr. Dongfang Liu, and Lixin Yan are employees of Sinocelltech Ltd. and have ownership or potential stock option interests in the company. All authors declare no other conflicts of interest. EDAT- 2022/12/06 06:00 MHDA- 2023/01/21 06:00 PMCR- 2022/12/05 CRDT- 2022/12/05 18:21 PHST- 2022/09/23 00:00 [received] PHST- 2022/11/01 00:00 [revised] PHST- 2022/11/16 00:00 [accepted] PHST- 2022/12/06 06:00 [pubmed] PHST- 2023/01/21 06:00 [medline] PHST- 2022/12/05 18:21 [entrez] PHST- 2022/12/05 00:00 [pmc-release] AID - S2352-3964(22)00568-0 [pii] AID - 104386 [pii] AID - 10.1016/j.ebiom.2022.104386 [doi] PST - ppublish SO - EBioMedicine. 2023 Jan;87:104386. doi: 10.1016/j.ebiom.2022.104386. Epub 2022 Dec 5.