A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 Omicron subvariants and other variants

Abstract

Multivalent vaccines combining crucial mutations from phylogenetically divergent variants could be an effective approach to defend against existing and future SARS-CoV-2 variants. In this study, we developed a tetravalent COVID-19 vaccine SCTV01E, based on the trimeric Spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1, with a squalene-based oil-in-water adjuvant SCT-VA02B. In the immunogenicity studies in naïve BALB/c and C57BL/6J mice, SCTV01E exhibited the most favorable immunogenic characteristics to induce balanced and broad-spectrum neutralizing potencies against pre-Omicron variants (D614G, Alpha, Beta, and Delta) and newly emerging Omicron subvariants (BA.1, BA.1.1, BA.2, BA.3, and BA.4/5). Booster studies in C57BL/6J mice previously immunized with D614G monovalent vaccine demonstrated superior neutralizing capacities of SCTV01E against Omicron subvariants, compared with the D614G booster regimen. Furthermore, SCTV01E vaccination elicited naïve and central memory T cell responses to SARS-CoV-2 ancestral strain and Omicron spike peptides. Together, our comprehensive immunogenicity evaluation results indicate that SCTV01E could become an important COVID-19 vaccine platform to combat surging infections caused by the highly immune evasive BA.4/5 variants. SCTV01E is currently being studied in a head-to-head immunogenicity comparison phase 3 clinical study with inactivated and mRNA vaccines (NCT05323461). Supporting Information The supporting information is available online at 10.1007/s11427-022-2207-7. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

Evaluation of the cross reactivity of neutralising antibody response in vaccinated human and convalescent hamster sera against SARS-CoV-2 variants up to and including JN.1 using an authentic virus neutralisation assay

“…All variants tested (CH.1.1, BQ.1.22, XBB.1.1, XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1.1, BA.2.86) displayed increased resistance to neutralisation to this four-dose panel relative to both ancestral and BA.4, with similar GM titres for all. This aligns with results presented by other groups using both pseudovirus (PSV) and authentic virus assays against panels of vaccinated (three- and four-dose) with additional break-through infection in a globally diverse population [53-60]. It is also of interest that the GM titres are comparable despite the genetic diversity in the variants tested against our four-dose panels.…”

COVID‐19 infection in patients with haematological malignancies: A single‐centre survey in the latest Omicron wave in China

“…Later in November 2021, the Omicron variant with enhanced immune escape was first reported from Botswana and thereafter from South Africa with an increased infection 1,2 . The SARS‐CoV‐2 Omicron BF.7 (BA.5.2.1.7), a subvariant of BA.5, has been responsible for the ongoing resurgence of cases since late September 2022 in China 3,4 . The mutations in the BF.7 variant spike glycoprotein, particularly those in the receptor‐binding domain have been associated with an increased immune escape capability to neutralize antibodies generated by vaccines or previous infection 5,6 .…”

“…1,2 The SARS-CoV-2 Omicron BF.7 (BA.5.2.1.7), a subvariant of BA.5, has been responsible for the ongoing resurgence of cases since late September 2022 in China. 3,4 The mutations in the BF.7 variant spike glycoprotein, particularly those in the receptor-binding domain have been associated with an increased immune escape capability to neutralize antibodies generated by vaccines or previous infection. 5,6 As a result, COVID-19 infection with BF.7 variant may cause a serious illness in populations with weaker immune systems such as the elderly and those suffering from concomitant comorbidities.…”

Enhanced neutralization of SARS-CoV-2 XBB sub-lineages and BA.2.86 by a tetravalent COVID-19 vaccine booster

“…China has initiated the rollout of its first quadrivalent COVID-19 vaccine, SCTV01E developed by Sinocelltech, aiming to tackle a resurging wave of infections driven by multiple SARS-CoV-2 variants. It is an Alpha/Beta/Delta/Omicron variants S-trimer vaccine 17 . Multiple clinical trials, conducted in China and the United Arab Emirates, have assessed its safety, tolerability, immunogenicity, and protective efficacy.…”