Abstract
Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, effective vaccines are essential to control the current coronavirus disease 2019 (COVID-19) pandemic. Plant-derived virus-like particle (VLP) vaccine candidates have previously demonstrated immunogenicity and efficacy against influenza. Here, we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein (CoVLP) vaccine candidate formulated with or without Adjuvant System 03 (AS03) or cytidine-phospho-guanosine (CpG) 1018. Although a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses, booster immunization (at 28 days after priming) and adjuvant administration significantly improved both responses, with higher immunogenicity and protection provided by the AS03-adjuvanted CoVLP. Fifteen micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2 (IL-2)-driven response and IL-4 expression in CD4 T cells. Animals were challenged by multiple routes (i.e., intratracheal, intranasal, and ocular) with a total viral dose of 106 plaque-forming units of SARS-CoV-2. Lower viral replication in nasal swabs and bronchoalveolar lavage fluid (BALF) as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with AS03. No clinical, pathologic, or virologic evidence of vaccine-associated enhanced disease was observed in vaccinated animals. The CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.
Highlights
INTRODUCTION InDecember 2019, a series of severe atypical respiratory disease cases occurred in Wuhan, China, and a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was rapidly identified as the causative agent of coronavirus disease 2019 (COVID-19)
The evidence of transient inflammation and mobilization of neutrophils in the blood of animals that received coronavirus-like particles (CoVLPs)+Adjuvant System 03 (AS03) are consistent with the inflammatory response observed upon vaccination with AS03adjuvanted vaccines [12,13,14]
The benefits of CpG 1018 or AS03 for the antibody response induced by COVID-19 vaccine candidates have been reported in nonhuman primate (NHP) and humans [19, 29, 30]
Summary
December 2019, a series of severe atypical respiratory disease cases occurred in Wuhan, China, and a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was rapidly identified as the causative agent of coronavirus disease 2019 (COVID-19). SARS-CoV-2 virions consist of a helical nucleocapsid formed by the association of nucleocapsid (N) phosphoproteins with viral genomic RNA that is surrounded by a lipid bilayer and three structural proteins, the spike (S), the membrane (M), and the envelope (E) proteins, are inserted into the nucleocapsid. The new coronavirus rapidly spread around the globe, resulting in the World Health Organization’s declaration of a pandemic on March 11, 2020. As of December 21, 2021, SARS-CoV-2 had caused over 275 million infections and more than 5.3 million deaths worldwide Therapeutics including monoclonal antibodies and antivirals have shown some therapeutic efficacy in limiting the burden of COVID-19, effective
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
