SARS-CoV-2 subunit vaccine adjuvants and their signaling pathways

ABSTRACT

Introduction

Vaccines are the agreed upon weapon against the COVID-19 pandemic. This review discusses about COVID-19 subunit vaccines adjuvants and their signaling pathways, which could provide a glimpse into the selection of appropriate adjuvants for prospective vaccine development studies.

Areas covered

In the introduction, a brief background about the SARS-CoV-2 pandemic, the vaccine development race and classes of vaccine adjuvants were provided. . The antigen, trial stage, and types of adjuvants were extracted from the included articles and thun assimilated. Finally, the pattern recognition receptors (PRRs), their classes, cognate adjuvants, and potential signaling pathways were comprehended.

Expert opinion

Adjuvants are unsung heroes of subunit vaccines. The in silico studies are very vital in avoiding several costly trial errors and save much work times. The majority of the (pre)clinical studies are promising. It is encouraging that most of the selected adjuvants are novel. Much emphasis must be paid to the optimal paring of antigen-adjuvant-PRRs for obtaining the desired vaccine effect. A good subunit vaccine/adjuvant is one that has high efficacy, safety, dose sparing, and rapid seroconversion rate and broad spectrum of immune response. In the years to come, COVID-19 adjuvanted subunit vaccines are expected to have superior utility than any other vaccines for various reasons.

KEYWORDS:

• SARS-CoV-2
• subunit vaccine
• adjuvants
• pattern recognition receptors
• signaling pathways

Supplementary material

Supplemental data for this article can be accessed here.

Article highlights

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an etiological agent of coronavirus disease-2019 (COVID-19), is ravaging the human race regardless of political and geographic boundary.

• Physicochemical characteristics (charge, size, and nature of chemical), immunological correlate of protection (the titer, kinship, isotype, dose sparing and seroconversion rate, and profile of cellular immune components) and safety, reactogenecity, and toxicity are the three-dimensional evaluation criteria employed for qualifying vaccines/ adjuvants.

• Among the 52 articles identified and examined, 27 distinct types of adjuvants were identified.

• Defensin, alum, Matrix-M1, CpG, and MF59 are the top five adjuvants on this list. By the same taken, Spike and RBD shared 43.6% and 33.8% of the candidate vaccine antigens. Spike proteins are more immunogenic than RBD.

• Novel COVID-19 vaccine adjuvants ensure host resistance by activating endosomal (Toll-like receptor 3/7/8/9) and cytosolic (RLRs and cGAS-STING) receptor signaling pathways.

• Nanoparticulate adjuvants have several important advantages over large molecules including antigen/nucleic acid delivery, limiting bioavailability, and depot effect.

• The effectiveness of subunit vaccines relies on the art of designing a vaccine, which has optimal antigen–adjuvant–PRR synergy pairing.

• Both pre-clinical and clinical trials confirmed the induction of several orders of magnitude of higher titer of neutralizing antibody than the convalescent sera of recovered people.

• The majority of the second generation COVID-19 vaccines might be the subunit vaccine types having the power of protection against the SARS-CoV-2, including emerging variants of concern.

Acknowledgments

The authors would like to express their thankfulness to the staff of the First Affiliated Hospital of USTC and colleagues in the TJ Lab of USTC for their encouragement and support.

Reviewer comments

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

D Mekonnen set the outline and subtopics, collected literatures, reviewed evidences, and drafted the manuscript, HM Mengist reviewed the draft and edited the manuscript. T Jin conceived the review topic, supervised the review process, reviewed, investigated, and validated the final manuscript. All authors read and approved the final manuscript.

Data availability statement

All datasets presented in this study and its supplementary materials are included in the submission.

Additional information

Funding

This manuscript was funded by the Strategic Priority Research Program of the Chinese Academy of Sciences (grant no. XDB29030104), the National Natural Science Foundation of China (grant no. 31870731 and 31971129), the Fundamental Research Funds for the Central Universities, and the 100 Talents Program of the Chinese Academy of Sciences. Daniel Mekonnen is supported by the ANSO scholarship. Hylemariam Mihiretie Mengist is supported by the USTC scholarship program.