دورية أكاديمية
أعرض في EDS

Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants.

التفاصيل البيبلوغرافية
العنوان: Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants.
المؤلفون: Mittal N; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru, 560012, India., Kumar S; Virology Unit, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Chandigarh, 160036, India., Rajmani RS; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru, 560012, India., Singh R; Mynvax Private Limited; 3rd Floor, Brigade MLR Centre, No.50, Vani Vilas Road, Basavanagudi, Bengaluru, 560004, India., Lemoine C; Vaccine Formulation Institute; Rue du Champ-Blanchod 4, 1228, Plan-les-Ouates, Switzerland., Jakob V; Vaccine Formulation Institute; Rue du Champ-Blanchod 4, 1228, Plan-les-Ouates, Switzerland., Bj S; Mynvax Private Limited; 3rd Floor, Brigade MLR Centre, No.50, Vani Vilas Road, Basavanagudi, Bengaluru, 560004, India., Jagannath N; Mynvax Private Limited; 3rd Floor, Brigade MLR Centre, No.50, Vani Vilas Road, Basavanagudi, Bengaluru, 560004, India., Bhat M; Mynvax Private Limited; 3rd Floor, Brigade MLR Centre, No.50, Vani Vilas Road, Basavanagudi, Bengaluru, 560004, India., Chakraborty D; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru, 560012, India., Pandey S; Mynvax Private Limited; 3rd Floor, Brigade MLR Centre, No.50, Vani Vilas Road, Basavanagudi, Bengaluru, 560004, India., Jory A; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, 560065, India., Sa SS; National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, 560065, India., Kleanthous H; Bill and Melinda Gates Foundation, Seattle, WA, 98109, USA., Dubois P; Vaccine Formulation Institute; Rue du Champ-Blanchod 4, 1228, Plan-les-Ouates, Switzerland., Ringe RP; Virology Unit, Institute of Microbial Technology, Council of Scientific and Industrial Research (CSIR), Chandigarh, 160036, India. rajeshringe@imtech.res.in., Varadarajan R; Molecular Biophysics Unit (MBU), Indian Institute of Science, Bengaluru, 560012, India. varadar@iisc.ac.in.
المصدر: NPJ vaccines [NPJ Vaccines] 2023 Oct 25; Vol. 8 (1), pp. 161. Date of Electronic Publication: 2023 Oct 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Springer Nature in partnership with the Sealy Center for Vaccine Development Country of Publication: England NLM ID: 101699863 Publication Model: Electronic Cited Medium: Internet ISSN: 2059-0105 (Electronic) Linking ISSN: 20590105 NLM ISO Abbreviation: NPJ Vaccines Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [London] : Springer Nature in partnership with the Sealy Center for Vaccine Development, [2016]-
مستخلص: With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly reactive immune responses that could improve protection. However, the contribution of the S2 subunit in improving the overall efficacy of vaccines remains unclear. Therefore, we designed, and evaluated the immunogenicity and protective potential of a stabilized SARS-CoV-2 Receptor Binding Domain (RBD) fused to a stabilized S2. Immunogens were expressed as soluble proteins with approximately fivefold higher purified yield than the Spike ectodomain and formulated along with Squalene-in-water emulsion (SWE) adjuvant. Immunization with S2 alone failed to elicit a neutralizing immune response, but significantly reduced lung viral titers in mice challenged with the heterologous Beta variant. In hamsters, SWE-formulated RS2 (a genetic fusion of stabilized RBD with S2) showed enhanced immunogenicity and efficacy relative to corresponding RBD and Spike formulations. Despite being based on the ancestral Wuhan strain of SARS-CoV-2, RS2 elicited broad neutralization, including against Omicron variants (BA.1, BA.5 and BF.7), and the clade 1a WIV-1 and SARS-CoV-1 strains. RS2 elicited sera showed enhanced competition with both S2 directed and RBD Class 4 directed broadly neutralizing antibodies, relative to RBD and Spike elicited sera. When lyophilized, RS2 retained antigenicity and immunogenicity even after incubation at 37 °C for a month. The data collectively suggest that the RS2 immunogen is a promising modality to combat SARS-CoV-2 variants.
(© 2023. Springer Nature Limited.)
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معلومات مُعتمدة: INV-005948 United States GATES Bill & Melinda Gates Foundation
تواريخ الأحداث: Date Created: 20231025 Latest Revision: 20240923
رمز التحديث: 20240923
مُعرف محوري في PubMed: PMC10600342
DOI: 10.1038/s41541-023-00755-2
PMID: 37880298
قاعدة البيانات: MEDLINE
الوصف
تدمد:2059-0105
DOI:10.1038/s41541-023-00755-2