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

Naru Zhang,Shuofeng Yuan,Jiawei Yao,Kaiming Tang,Haotian Shang,Kangchen Li,Shibo Jiang,Zecan Shi,Sisi Li,Yubin Xie,Lu Lu,Qianting Ji,Jie Zhou,Zezhong Liu,Tianyu Zheng

doi:10.3390/v14030501

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.

Highlights

Coronavirus disease 2019 (COVID-19), which is caused by the pathogen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become increasingly serious as a result of the continuous emergence of variants of concern (VOC), including B.1.1.7 (Alpha) [1], B.1.351 (Beta) [2], P.1 (Gamma) [3], B.1.617.2 (Delta) [4] and B.1.1.529 (Omicron) [5]
We evaluated the effects of nanoparticle manganese, MF59 and alum adjuvants on the induction of host immune responses by using RBD-Fc, RBD and S-trimer of SARS-CoV-2 as antigens in BALB/c mice
Mice were intramuscularly vaccinated with RBD-Fc, RBD or S-trimer plus alum, MF59 or nanoparticle manganese adjuvant three times at two-week intervals

Summary

Introduction

Coronavirus disease 2019 (COVID-19), which is caused by the pathogen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become increasingly serious as a result of the continuous emergence of variants of concern (VOC), including B.1.1.7(Alpha) [1], B.1.351 (Beta) [2], P.1 (Gamma) [3], B.1.617.2 (Delta) [4] and B.1.1.529 (Omicron) [5]. Coronavirus disease 2019 (COVID-19), which is caused by the pathogen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become increasingly serious as a result of the continuous emergence of variants of concern (VOC), including B.1.1.7. Scientific consensus is growing that current vaccines show relatively low neutralizing immunogenicity, no broad-spectrum efficacy, and little lasting protective immunity [8]. To address this grim outlook, the development of more effective, long-lasting and broad-spectrum vaccines is essential. Multimeric display of antigens in combination with a powerful adjuvant could enhance the longevity and potency of induced immune responses in hosts. Adjuvanted vaccines could induce more effective, broad-spectrum and durable protective immunity against SARS-CoV-2 and its emerging variants

Methods

Results

Conclusion