Effect of Different Adjuvants on Immune Responses Elicited by Protein-Based Subunit Vaccines against SARS-CoV-2 and Its Delta Variant

Abstract

The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become more serious because of the continuous emergence of variants of concern (VOC), thus calling for the development of broad-spectrum vaccines with greater efficacy. Adjuvants play important roles in enhancing the immunogenicity of protein-based subunit vaccines. In this study, we compared the effect of three adjuvants, including aluminum, nanoparticle manganese and MF59, on the immunogenicity of three protein-based COVID-19 vaccine candidates, including RBD-Fc, RBD and S-trimer. We found that the nanoparticle manganese adjuvant elicited the highest titers of SARS-CoV-2 RBD-specific IgG, IgG1 and IgG2a, as well as neutralizing antibodies against infection by pseudotyped SARS-CoV-2 and its Delta variant. What is more, the nanoparticle manganese adjuvant effectively reduced the viral load of the authentic SARS-CoV-2 and Delta variant in the cell culture supernatants. These results suggest that nanoparticle manganese, known to facilitate cGAS-STING activation, is an optimal adjuvant for protein-based COVID-19 subunit vaccines.

A six-month study of anti-SARS-CoV-2 BNT162b2 mRNA vaccination: A comparative analysis of essential trace elements and anti-RBD IgG sera levels

“…No significant changes in serum Cu levels were recorded before and after vaccination. As Cu and Zn are antagonists during the absorption process in the gastrointestinal tract (GIT), higher Cu levels in the GIT could be expected to reduce Zn levels [9] . However, the opposite is also true, as zinc intake in high doses (> 150 mg/day) can result in Cu deficiency in healthy individuals [30] .…”

“…Following a SARS-CoV-2 infection, most patients develop detectable specific IgG antibodies to the receptor-binding domain (RBD) of the viral spike glycoprotein and associated neutralizing activities [1] , [3] , [5] , [8] , [9] . In addition, most infected persons develop detectable IgG levels to structural SARS-CoV-2 antigens that can persist for more than six months post-acute infection [10] , [11] , [12] , [13] .…”

The Occluded Epitope Residing in Spike Receptor-Binding Motif Is Essential for Cross-Neutralization of SARS-CoV-2 Delta Variant

“…The RBD vaccination strategy demonstrated a significant impact on eliciting elevated cross-neutralizing antibody titers, with subsequent protection against viral variants and the potential to limit community transmission [45]. Zhang et al (2022) investigated the effect of adjuvants on the immunogenicity of three COVID-19 vaccine candidates, based on proteins, including RBD-Fc, RBD, and S-trimer [46]. The feasibility of inducing protective immunity against Omicron and future emerging sarbecoviruses relying on RBD was recently reported by Lui et al (2022) [47].…”

Development of variant‐proof severe acute respiratory syndrome coronavirus 2, pan‐sarbecovirus, and pan‐β‐coronavirus vaccines

“…Compared with RBD and S‐trimer, we found that RBD‐Fc homodimer effectively elicited more potent RBD‐specific IgG and neutralizing antibodies against SARS‐CoV‐2 and its Delta variant in mice. 61 Moreover, a COVID‐19 RBD‐dimer‐based protein subunit vaccine candidate, ZF2001, 62 exhibited high protective efficacy (more than 80%) in preventing symptomatic COVID‐19 in phase 3 clinical trials. 63 Recent studies have demonstrated that it could induce increased titers of nAbs against Omicron after administration of multiple booster doses.…”