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Article | Open Access

Safety, immunogenicity, and preliminary efficacy of a randomized clinical trial of omicron XBB.1.5-containing bivalent mRNA vaccine

Xuanjing Yu1,2,#, Wei Yang1,#, Wei Li3,4,#, Na Wan1,2, Guanghong Yan5, Zumi Zhou6, Xiao Zhu6, Wei Su6, Yani Li5, Chenyu Xing5, Sifan Duan5, Houze Yu1,2, Xinshuai Zhao1, Chunmei Li1, Taicheng Zhou7( ), Dingyun You5( ), Jia Wei7( ), Zijie Zhang1,2,4( )
State Key Laboratory for Conservation and Utilization of Bio-Resource and School of Life Sciences, Yunnan University, Yunnan, China
Southwest United Graduate School, Yunnan, China
State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China
Yunnan Vaccine Laboratory, Yunnan, China
School of Public Health, Kunming Medical University, Yunnan, China
Yunnan Genvoo Biotech Ltd., Yunnan, China
Central Lab and Liver Disease Research Center, The Affiliated Hospital of Yunnan University, Yunnan University, Yunnan, China

#These authors contributed equally to this work

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Highlights

● XBB.1.5-containing bivalent generated superior immunogenicity against XBB lineages compared to BA.2/BA.5-containing bivalent.

● The efficacy of booster dose against XBB lineages waned after 2-3 months.

● Newer variant-matched vaccine elicits an enhanced immune response against newly emerged variants.

Graphical Abstract

Abstract

Periodically updating coronavirus disease 19 (COVID-19) vaccines that offer broad-spectrum protection is needed given the strong immune evasion by the circulating omicron sublineages. The effectiveness of prototype and BA.4/5-containing bivalent mRNA vaccines is reduced when XBB subvariants predominate. We initiated an observer-blinded, three-arms study in 376 patients in Chinese individuals aged from 18 to 55 years old who had previously received three doses COVID-19 vaccine. Immunogenicity in terms of neutralizing antibodies elicited by a 30-μg dose of XBB.1.5-containing bivalent vaccine (RQ3027), a 30-μg dose of BA.2/BA.5-Alpha/Beta bivalent vaccine (RQ3025) and their precedent 30-μg Alpha/Beta (combined mutations) monovalent mRNA vaccine (RQ3013) and safety are primary and secondary endpoints, respectively. We recorded prescribed COVID-19 cases to explore the preliminary efficacy of three vaccines. RQ3027 and RQ3025 boosters elicited superior neutralizing antibodies (NAbs) against XBB.1.5, XBB.1.16, XBB.1.9.1, and JN.1 compared to RQ3013 at day 14 in participants without SARS-CoV-2 infection. All study vaccines were well-tolerated without serious adverse reactions identified. The incidence rates per 1000 person-years of COVID-19 cases during the 2nd-19th week after randomization were lowest in RQ3027. Overall, our data show that XBB.1.5-containing bivalent booster generated superior immunogenicity and better protection against newer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants compared to BA.2/BA.5-containing bivalent and Alpha/Beta monovalent with no new safety concerns.

Keywords

severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)randomized clinical trialJN.1XBB lineagescoronavirus disease 19 (COVID-19) vaccinemRNA bivalent vaccine

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hLife
Volume 2 Issue 3,
March 2024
Pages 113-125
DOI: 10.1016/j.hlife.2024.01.005
Cite this article:
Yu X, Yang W, Li W, et al. Safety, immunogenicity, and preliminary efficacy of a randomized clinical trial of omicron XBB.1.5-containing bivalent mRNA vaccine. hLife, 2024, 2(3): 113-125. https://doi.org/10.1016/j.hlife.2024.01.005

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Received: 16 December 2023
Revised: 26 January 2024
Accepted: 26 January 2024
Published: 01 February 2024
© 2024 The Author(s).

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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