Safety and immunogenicity of boosting with a severe acute respiratory syndrome coronavirus 2 omicron variant mRNA vaccine in healthy adults: An open-label, and single-arm Phase 1 study.
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ABSTRACT:
SUBMITTER: Hannawi S
PROVIDER: S-EPMC10447877 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Safety and immunogenicity of boosting with a severe acute respiratory syndrome coronavirus 2 omicron variant mRNA vaccine in healthy adults: An open-label, and single-arm Phase 1 study.
Hannawi Suad S Zhang Rong-Rong RR Abuquta Alaa A Safeldin Linda L Hassan Aala A Alamadi Ahmad A Hossain Tasmiah T Mostafa Mohamed M Ghoneim Yasser Y Solo Jennifer J Zheng Hong-Xia HX Wu Ding-Feng DF Yu Dan-Dan DD Yuan Jia-Cheng JC Zhao Di D Lin Rui R Ying Bo B Qin Cheng-Feng CF
Clinical and translational medicine 20230801 8
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Project description:ObjectiveTo evaluate the efficacy and safety of leflunomide for the treatment of acute, symptomatic COVID-19.MethodsA single-center, open-label, randomized controlled trial was performed during an outbreak of SARS-CoV-2 Omicron variant in December 2022. Symptomatic patients within 5 days of COVID-19 onset were randomly allocated to receive 5 days of either symptomatic treatment with leflunomide or symptomatic treatment alone. The primary endpoint was time to sustained clinical recovery.ResultsFifty-seven participants were randomized into two groups: 27 received leflunomide plus symptomatic treatment and 30 were assigned to symptomatic treatment alone. Participants treated with leflunomide had a shorter fever duration [3.0 interquartile range (IQR, 2.0-4.0) days and 4.0 (IQR, 3.0-6.0) days, respectively (p = 0.027)] and reduced viral shedding [7 (IQR, 6-9.5) days and 9.0 (IQR, 7.5-12.0) days, respectively (p = 0.044)] compared with individuals treated with symptomatic treatment alone. However, there were no significant differences in time to sustained clinical recovery between the two groups [hazard ratio, 1.329 (95% confidence interval, 0.878-2.529); p = 0.207].ConclusionIn acute adult COVID-19 patients presenting within 5 days of symptom onset, leflunomide combined with symptomatic treatment reduced fever duration and viral shedding time.Clinical trial registrationhttps://www.chictr.org.cn/about.html, ChiCTR2100051684.
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Project description:The newly emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains more than 30 mutations on the spike protein, 15 of which are located within the receptor binding domain (RBD). Consequently, Omicron is able to extensively escape existing neutralizing antibodies and may therefore compromise the efficacy of current vaccines based on the original strain, highlighting the importance and urgency of developing effective vaccines against Omicron. Here we report the rapid generation and evaluation of an mRNA vaccine candidate specific to Omicron, and explore the feasibility of heterologous immunization with WT and Omicron RBD vaccines. This mRNA vaccine encodes the RBD of Omicron (designated as RBD-O) and is formulated with lipid nanoparticle. Two doses of the RBD-O mRNA vaccine efficiently induce neutralizing antibodies in mice; however, the antisera are effective only on the Omicron variant but not on the wildtype and Delta strains, indicating a narrow neutralization spectrum. It is noted that the neutralization profile of the RBD-O mRNA vaccine is opposite to that observed for the mRNA vaccine expressing the wildtype RBD (RBD-WT). Importantly, booster with RBD-O mRNA vaccine after two doses of RBD-WT mRNA vaccine can significantly increase neutralization titers against Omicron. Additionally, an obvious increase in IFN-γ, IL-2, and TNF-α-expressing RBD-specific CD4+ T cell responses was observed after immunization with the RBD-WT and/or RBD-O mRNA vaccine. Together, our work demonstrates the feasibility and potency of an RBD-based mRNA vaccine specific to Omicron, providing important information for further development of heterologous immunization program or bivalent/multivalent SARS-CoV-2 vaccines with broad-spectrum efficacy.
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