Distinguishing features of current COVID-19 vaccines: knowns and unknowns of antigen presentation and modes of action

Abstract

COVID-19 vaccines were developed with an unprecedented pace since the beginning of the pandemic. Several of them have reached market authorization and mass production, leading to their global application on a large scale. This enormous progress was achieved with fundamentally different vaccine technologies used in parallel. mRNA, adenoviral vector as well as inactivated whole-virus vaccines are now in widespread use, and a subunit vaccine is in a final stage of authorization. They all rely on the native viral spike protein (S) of SARS-CoV-2 for inducing potently neutralizing antibodies, but the presentation of this key antigen to the immune system differs substantially between the different categories of vaccines. In this article, we review the relevance of structural modifications of S in different vaccines and the different modes of antigen expression after vaccination with genetic adenovirus-vector and mRNA vaccines. Distinguishing characteristics and unknown features are highlighted in the context of protective antibody responses and reactogenicity of vaccines.

Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine

“…However, relative immunogenicity of a third dose seemed to be diminished against all 3 variants (especially the Beta variant) versus wild-type virus. The latter finding is consistent with data in healthy immunocompetent populations and likely relates to the fact that mRNA vaccines are manufactured based on the wild-type virus spike protein sequence ( 19 ). Taken together, the current data provide further support for a third vaccine dose in immunocompromised patients, even when current VOCs, such as the Delta variant, are the dominant circulating SARS-CoV-2 strains in the community.…”

Ocular Manifestations after Receiving COVID-19 Vaccine: A Systematic Review

“…The COVID-19 vaccines included in these studies are mRNA vaccines and adenoviral vector vaccines, both of which do not contain the spike protein. Instead, these contain genetic information about the spike protein for its biosynthesis in body cells [41].…”

“…The mRNA vaccines, including BNT162b2 and mRNA-1273, contain codon-optimized sequences for spike protein synthesis and use the authentic signal sequence for its biosynthesis [41]. The mRNA is delivered in lipid nanoparticles and induce the production of proin-flammatory cytokines, such as interferon gamma (IFNγ), antigen-specific CD4+ and CD8+ T cell responses, and anti-spike neutralizing antibody.…”

“…However, evidence has shown that during transcription, alternative splice events might cause the formation of Cterminally truncated, which may lead to formation of soluble spike protein. These soluble spike variants may induce thrombotic events via an antibody-mediated mechanism when binding to ACE2-expressing endothelial cells in blood vessels [41,45]. Other possible causes of thrombosis include spike protein interactions with different C-type lectin receptors, heparan sulfate proteoglycans, and the CD147 receptor.…”

A recombinant SARS-CoV-2 RBD antigen expressed in insect cells elicits immunogenicity and confirms safety in animal models

“…In addition, it generates antibodies with enhanced neutralizing activity [22][23][24]. The greater accumulation of mutations in the S1 and S2 domains can destabilize the protein, hindering its production and the yields obtained as a purified protein [25,26]. On the other hand, RBD has demonstrated an easier production [27], and results in a more conserved antigen.…”