SARS-CoV-2 protein subunit vaccination of mice and rhesus macaques elicits potent and durable neutralizing antibody responses

Marco Mandolesi,Daniel J Sheward,Leo Hanke,Junjie Ma,Pradeepa Pushparaj,Laura Perez Vidakovics,Changil Kim,Monika Àdori,Klara Lenart,Karin Loré,Xaquin Castro Dopico,Jonathan M Coquet,Gerald M Mcinerney,Gunilla B Karlsson Hedestam,Ben Murrell

doi:10.1016/j.xcrm.2021.100252

Marco Mandolesi, Daniel J Sheward + Show 13 more

Open Access

https://doi.org/10.1016/j.xcrm.2021.100252

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Abstract

SummaryThe outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. The spike glycoprotein of SARS-CoV-2 mediates entry into host cells, and thus is the target of neutralizing antibodies. Here, we show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines.

Highlights

As of February 2021, over 109 million cases of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection have been confirmed, with more than 2.4 million coronavirus disease 2019 (COVID-19)-related deaths recorded.[1]
While the receptor-binding domain (RBD) is a major target for neutralizing antibodies,[9,10,11] antibodies specific for spike epitopes outside the RBD are capable of neutralization.[12,13]
We examined the neutralizing antibody responses elicited in immunized macaques against the D614G variant and observed neutralizing titers that were comparable those observed against the wild-type strain (Figure S1I)

Summary

SUMMARY

The outbreak and spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) is a current global health emergency, and effective prophylactic vaccines are needed urgently. We show that adjuvanted protein immunization with soluble SARS-CoV-2 spike trimers, stabilized in prefusion conformation, results in potent antibody responses in mice and rhesus macaques, with neutralizing antibody titers exceeding those typically measured in SARS-CoV-2 seropositive humans by more than one order of magnitude. Neutralizing antibody responses were observed after a single dose, with exceptionally high titers achieved after boosting. A follow-up to monitor the waning of the neutralizing antibody responses in rhesus macaques demonstrated durable responses that were maintained at high and stable levels at least 4 months after boosting. These data support the development of adjuvanted SARS-CoV-2 prefusion-stabilized spike protein subunit vaccines

INTRODUCTION

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Findings

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