COVID-19 vaccine update: vaccine effectiveness, SARS-CoV-2 variants, boosters, adverse effects, and immune correlates of protection

Abstract

Coronavirus Disease 2019 (COVID-19) has been the most severe public health challenge in this century. Two years after its emergence, the rapid development and deployment of effective COVID-19 vaccines have successfully controlled this pandemic and greatly reduced the risk of severe illness and death associated with COVID-19. However, due to its ability to rapidly evolve, the SARS-CoV-2 virus may never be eradicated, and there are many important new topics to work on if we need to live with this virus for a long time. To this end, we hope to provide essential knowledge for researchers who work on the improvement of future COVID-19 vaccines. In this review, we provided an up-to-date summary for current COVID-19 vaccines, discussed the biological basis and clinical impact of SARS-CoV-2 variants and subvariants, and analyzed the effectiveness of various vaccine booster regimens against different SARS-CoV-2 strains. Additionally, we reviewed potential mechanisms of vaccine-induced severe adverse events, summarized current studies regarding immune correlates of protection, and finally, discussed the development of next-generation vaccines.

Keywords: COVID-19; Immunity; SARS-CoV-2; Vaccine; Variant.

Fig. 1

Components of Vaccines with WHO EUL. Covid-19 vaccines with WHO EUL are grouped into four main categories based on the component of individual vaccines: RNA, inactivated virus, non-replicating viral vector and protein subunit. (Created with BioRender.com)

Fig. 2

Viral variant and mutations. Amino acid alterations to the spike protein in SARS-CoV-2 VoCs. Domain composition of SARS-CoV-2 spike protein is shown in the bottom [118, 291]. Circles indicate point mutations or insertions; crosses indicate deletions

Fig. 3

The cartoon depiction of the SARS-CoV-2 spike protein trimer and the mutating amino acids. The 3D structure of SARS-CoV-2 spike protein trimer in the closed prefusion configuration (modified from PDB 6VXX) is shown in top (left panel) and side views (right panel). a One of the spike protein monomers is shown in the ribbon diagram with the NTD, the RBD, and the S2 domain of the spike protein are colored in blue, green and gray, respectively. Whereas the other two spike monomers are shown as surface and colored in cyan and yellow, respectively. b–f The mutating amino acid residues in each variant are highlighted as red spheres. The NTD, RBD, and the S2 domain of the spike protein are colored in blue, green and grey in the ribbon diagram, respectively

Fig. 4

Potential mechanism of VITT. After vaccination, the viral proteins in the vaccine components might bind with PF4, thereby forming epitopes that can be recognized by the immune system and inducing the generation of anti-PF4 antibodies. Anti-PF4 antibodies form immune complexes with PF4 and bind with the Fc receptor on the surface of the platelet, leading to platelet activation and aggregation, and finally VITT 5 to 20 days after vaccination. (Created with BioRender.com)