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Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
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Journal Article
Adjuvanting a subunit COVID-19 vaccine to induce protective immunity
2021
Overview
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative
1
. Here we demonstrate the capacity of a subunit vaccine, comprising the SARS-CoV-2 spike protein receptor-binding domain displayed on an I53-50 protein nanoparticle scaffold (hereafter designated RBD–NP), to stimulate robust and durable neutralizing-antibody responses and protection against SARS-CoV-2 in rhesus macaques. We evaluated five adjuvants including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an α-tocopherol-containing oil-in-water emulsion; AS37, a Toll-like receptor 7 (TLR7) agonist adsorbed to alum; CpG1018-alum, a TLR9 agonist formulated in alum; and alum. RBD–NP immunization with AS03, CpG1018-alum, AS37 or alum induced substantial neutralizing-antibody and CD4 T cell responses, and conferred protection against SARS-CoV-2 infection in the pharynges, nares and bronchoalveolar lavage. The neutralizing-antibody response to live virus was maintained up to 180 days after vaccination with RBD–NP in AS03 (RBD–NP-AS03), and correlated with protection from infection. RBD–NP immunization cross-neutralized the B.1.1.7 SARS-CoV-2 variant efficiently but showed a reduced response against the B.1.351 variant. RBD–NP-AS03 produced a 4.5-fold reduction in neutralization of B.1.351 whereas the group immunized with RBD–NP-AS37 produced a 16-fold reduction in neutralization of B.1.351, suggesting differences in the breadth of the neutralizing-antibody response induced by these adjuvants. Furthermore, RBD–NP-AS03 was as immunogenic as a prefusion-stabilized spike immunogen (HexaPro) with AS03 adjuvant. These data highlight the efficacy of the adjuvanted RBD–NP vaccine in promoting protective immunity against SARS-CoV-2 and have led to phase I/II clinical trials of this vaccine (NCT04742738 and NCT04750343).
Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Agonists
/ Animals
/ Antibodies, Neutralizing - immunology
/ Antibodies, Viral - immunology
/ Antigens
/ Bronchus
/ CD4-Positive T-Lymphocytes - cytology
/ CD4-Positive T-Lymphocytes - immunology
/ Clinical Trials, Phase I as Topic
/ Clinical Trials, Phase II as Topic
/ COVID-19
/ COVID-19 - prevention & control
/ COVID-19 Vaccines - immunology
/ Humanities and Social Sciences
/ Immunity
/ Male
/ Proteins
/ Science
/ Severe acute respiratory syndrome coronavirus 2
/ Spike Glycoprotein, Coronavirus - chemistry
/ Spike Glycoprotein, Coronavirus - immunology
/ Squalene
/ Vaccines
