scispace - formally typeset
Open AccessJournal ArticleDOI

Adjuvanting a subunit COVID-19 vaccine to induce protective immunity.

TLDR
In this article, the authors 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.
Abstract
The development of a portfolio of COVID-19 vaccines to vaccinate the global population remains an urgent public health imperative1. 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).

read more

Content maybe subject to copyright    Report

Citations
More filters
Posted ContentDOI

A booster dose of mRNA-based COVID-19 vaccines fosters the development of an immune response in immunosuppressed fragile patients.

TL;DR: It is found that fragile patients, depending on the type of treatment, poorly respond to SARS-CoV-2 mRNA vaccines, however, an additional booster dose of vaccine induced a good immune response in almost all of the patients except those receiving anti-CD20 antibody.
Posted ContentDOI

Broad and Durable Humoral Responses Following Single Hydrogel Immunization of SARS-CoV-2 Subunit Vaccine

TL;DR: In this paper , a single immunization SARS-CoV-2 subunit vaccine that could rapidly generate potent, broad, and durable humoral immunity was developed, which leveraged injectable polymer-nanoparticle (PNP) hydrogels as a depot technology for the sustained delivery of a nanoparticle COVID antigen displaying multiple copies of the RBD-NP.
Journal ArticleDOI

Single-cell sequencing of PBMC characterizes the altered transcriptomic landscape of classical monocytes in BNT162b2-induced myocarditis

TL;DR: The importance of classical monocytes in the pathogenesis of myocarditis following BNT162b2 vaccination is provided for the first time and the possibility that vaccination affects monocytes, further inducing their differentiation and infiltration into the heart is presented.
Journal ArticleDOI

Systems serology-based comparison of antibody effector functions induced by adjuvanted vaccines to guide vaccine design

TL;DR: In this article , the role of adjuvants in shaping the maturation of antibody effector functions remains under investigated, using systems serology, using adjvants in licensed vaccines (AS01 B /AS01 E /AS03/AS04/Alum) combined with a model antigen.
References
More filters
Journal ArticleDOI

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.

TL;DR: It is demonstrating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination, and it is shown that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of Sars- coV- 2 S and SARS S bind with similar affinities to human ACE2, correlating with the efficient spread of SATS among humans.
Journal ArticleDOI

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

Merryn Voysey, +81 more
- 09 Jan 2021 - 
TL;DR: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.
Journal ArticleDOI

The Architecture of SARS-CoV-2 Transcriptome.

TL;DR: Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to the understanding of the life cycle and pathogenicity of SARS-CoV-2.
Related Papers (5)