SARS-CoV-2 vaccines: a triumph of science and collaboration

Abstract

Roughly 1 year after the first case of COVID-19 was identified and less than 1 year after the sequencing of SARS-CoV-2, multiple SARS-CoV-2 vaccines with demonstrated safety and efficacy in phase III clinical trials are available. The most promising vaccines have targeted the surface glycoprotein (S-protein) of SARS-CoV-2 and achieved an approximate 85%-95% reduction in the risk of symptomatic COVID-19, while retaining excellent safety profiles and modest side effects in the phase III clinical trials. The mRNA, replication-incompetent viral vector, and protein subunit vaccine technologies have all been successfully employed. Some novel SARS-CoV-2 variants evade but do not appear to fully overcome the potent immunity induced by these vaccines. Emerging real-world effectiveness data add evidence for protection from severe COVID-19. This is an impressive first demonstration of the effectiveness of the mRNA vaccine and vector vaccine platforms. The success of SARS-CoV-2 vaccine development should be credited to open science, industry partnerships, harmonization of clinical trials, and the altruism of study participants. The manufacturing and distribution of the emergency use-authorized SARS-CoV-2 vaccines are ongoing challenges. What remains now is to ensure broad and equitable global vaccination against COVID-19.

Figure 1. SARS-CoV-2 vaccine platforms.

A schematic representation of the major SARS-CoV-2 vaccine platforms under active development as of February 2021. Adenoviral vector vaccines refer to replication-incompetent adenoviral-based vectors. All candidate vaccines (aside from whole inactivated virus) target the binding domain of the SARS-CoV-2 spike (S) protein. Both mRNA and vector vaccines target muscle cells at the site of injection. The muscle cells produce (portions of the) SARS-CoV-2 spike protein, which is in turn presented via MHC class I to antigen-presenting cells and cytotoxic T cells. In contrast, protein subunit vaccines and inactivated viral vaccines are directly taken up by antigen-presenting cells. The antigen-presenting cells in turn present the spike protein antigen to T helper cells and B cells, resulting in an orchestrated humoral and cellular immune response against the spike protein of SARS-CoV-2, including the generation of memory T cells and B cells to respond to future exposures to SARS-CoV-2. Illustrated by Rachel Davidowitz.

Figure 2. Comparison of the efficacy of COVID-19 vaccines as presented in the interim analyses of phase III clinical trials.

All results are based on cases that occurred at least 2 weeks after the final vaccine dose. CIs are calculated using the Clopper and Pearson method (51) and are not adjusted for differences in the underlying study populations. The left panel shows the estimated efficacy against the FDA-harmonized case definition for symptomatic COVID-19 (any COVID-19 symptoms and a confirmation of SARS-CoV-2 infection via RT-PCR testing). The right panel shows the estimated efficacy against severe/critical COVID-19. The wide CIs for some of the vaccines are due to the small number of severe cases at the time of interim analysis. Illustrated by Rachel Davidowitz.

Figure 3. Frequency of common adverse events after vaccination, as reported in the interim analyses of the phase III trials.

All events are solicited adverse events, aside from chills and joint pain for Ad26.COV2.S, which were nonsolicited. APAP, acetaminophen. Illustrated by Rachel Davidowitz.