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Evaluation of candidate vaccine approaches for MERS-CoV.

ABSTRACT: The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

SUBMITTER: Wang L

PROVIDER: S-EPMC4525294 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Evaluation of candidate vaccine approaches for MERS-CoV.

Wang Lingshu L Shi Wei W Joyce M Gordon MG Modjarrad Kayvon K Zhang Yi Y Leung Kwanyee K Lees Christopher R CR Zhou Tongqing T Yassine Hadi M HM Kanekiyo Masaru M Yang Zhi-yong ZY Chen Xuejun X Becker Michelle M MM Freeman Megan M Vogel Leatrice L Johnson Joshua C JC Olinger Gene G Todd John P JP Bagci Ulas U Solomon Jeffrey J Mollura Daniel J DJ Hensley Lisa L Jahrling Peter P Denison Mark R MR Rao Srinivas S SS Subbarao Kanta K Kwong Peter D PD Mascola John R JR Kong Wing-Pui WP Graham Barney S BS

Nature communications 20150728

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serum-neutralizing activity against several MERS-CoV strains in mice ...[more]

PMID: 26218507

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Project description:COVID-19 caused by SARS-CoV-2 was declared a global pandemic by WHO (World Health Organization) in March, 2020. Within 6 months, nearly 750,000 deaths are claimed by COVID-19 across the globe. This called for immediate social, scientific, technological, public and community interventions. Considering the severity of infection and the associated mortalities, global efforts are underway to develop preventive measures against SARS-CoV-2. Among the SARS-CoV-2 target proteins, Spike (S) glycoprotein (a.k.a S Protein) is the most studied target known to trigger strong host immune response. A detailed analysis of S protein-based epitopes enabled us to design a novel B-cell-derived T-cell Multi-epitope-based peptide (MEBP) vaccine candidate. This involved a systematic and comprehensive computational protocol consisting of prediction of dual-purpose epitopes and designing an MEBP vaccine construct. This was followed by 3D structure validation, MEBP complex interaction studies, in silico cloning and vaccine dose-based immune response simulation to evaluate the immunogenic potency of the vaccine construct. The dual-purpose epitope prediction protocol was designed such that the same epitope elicits both humoral and cellular immune response unlike the earlier designs. Further, the epitopes predicted were screened against stringent criteria to ensure selection of a potent candidate with maximum antigen coverage and best immune response. The vaccine dose-based immune response simulation studies revealed a rapid antigen clearance through antibody generation and elevated levels of cell-mediated immunity during repeated exposure of the vaccine. The favourable results of the analysis strongly indicate that the vaccine construct is indeed a potent vaccine candidate and ready to proceed to the next steps of experimental validation and efficacy studies.Supplementary informationThe online version contains supplementary material available at 10.1007/s13205-020-02574-x.

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Evaluation of candidate vaccine approaches for MERS-CoV.

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Evaluation of candidate vaccine approaches for MERS-CoV.

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