Robust induction of functional humoral response by a plant-derived Coronavirus-like particle vaccine candidate for COVID-19

Abstract

Despite the success of existing COVID-19 vaccine platforms, the persistent limitations in global deployment of vaccines and waning immunity exhibited by many of the currently deployed vaccine platforms have led to perpetual outbreaks of SARS-CoV-2 variants of concern. Thus, there is an urgent need to develop new durable vaccine candidates, to expand the global vaccine pipeline, and provide safe and effective solutions for every country worldwide. Here we deeply profiled the functional humoral response induced by two doses of AS03-adjuvanted and non-adjuvanted plant-derived Coronavirus-like particle (CoVLP) vaccine candidate from the phase 1 clinical trial, at peak immunogenicity and six months post-vaccination. AS03-adjuvanted CoVLP induced robust and durable SARS-CoV-2 specific humoral immunity, marked by strong IgG1antibody responses, potent FcγR binding, and antibody effector function. Contrary to a decline in neutralizing antibody titers, the FcγR2A-receptor binding capacity and antibody-mediated effector functions, such as opsonophagocytosis, remained readily detectable for at least six months.

Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations

“…This may be highly advantageous for the design of precision vaccines tailored to the unique requirements of distinct immunologically vulnerable populations. Most notably, emulsion adjuvants, such as MF59 and AS03, as well as toll-like receptor (TLR) agonist adjuvants, particularly when used in combination, have been advantageous for generating polyfunctional antibodies and further boosting Fc functional capacity of nanoparticle-based vaccines ( 467 , 482 , 483 ). Nevertheless, comprehensive studies that systematically compare the impact of a spectrum of adjuvants upon Fc functions are lacking.…”

To be remembered: B cell memory response against SARS‐CoV‐2 and its variants in vaccinated and unvaccinated individuals

“…A study about the immunogenicity of AS03-adjuvanted VLP-based vaccine suggests that the Th2-type response triggered by VLPs could contribute to high levels of neutralizing antibodies and enduring memory B cell responses. 97,98 Besides significant development in the field of VLPbased vaccine platforms, most of the other vaccines developed against SARS-CoV-2 were studied in animal models. [99][100][101] There is only limited scientific knowledge available regarding their memory B cell response in humans as of now.…”

“…These VLPs offer a distinct presentation of functional antigens, resembling natural infections and possibly stimulating highly effective B cell immune reactions. A study about the immunogenicity of AS03‐adjuvanted VLP‐based vaccine suggests that the Th2‐type response triggered by VLPs could contribute to high levels of neutralizing antibodies and enduring memory B cell responses 97,98 . Besides significant development in the field of VLP‐based vaccine platforms, most of the other vaccines developed against SARS‐CoV‐2 were studied in animal models 99–101 .…”