COVID-19 Variants and Vaccine Development

Abstract

Coronavirus disease 2019 (COVID-19), the global pandemic caused by severe acute respiratory syndrome 2 virus (SARS-CoV-2) infection, has caused millions of infections and fatalities worldwide. Extensive SARS-CoV-2 research has been conducted to develop therapeutic drugs and prophylactic vaccines, and even though some drugs have been approved to treat SARS-CoV-2 infection, treatment efficacy remains limited. Therefore, preventive vaccination has been implemented on a global scale and represents the primary approach to combat the COVID-19 pandemic. Approved vaccines vary in composition, although vaccine design has been based on either the key viral structural (spike) protein or viral components carrying this protein. Therefore, mutations of the virus, particularly mutations in the S protein, severely compromise the effectiveness of current vaccines and the ability to control COVID-19 infection. This review begins by describing the SARS-CoV-2 viral composition, the mechanism of infection, the role of angiotensin-converting enzyme 2, the host defence responses against infection and the most common vaccine designs. Next, this review summarizes the common mutations of SARS-CoV-2 and how these mutations change viral properties, confer immune escape and influence vaccine efficacy. Finally, this review discusses global strategies that have been employed to mitigate the decreases in vaccine efficacy encountered against new variants.

Keywords: COVID-19; SARS-CoV-2; mutations; vaccination; vaccine effectiveness; variants.

Figure 1

Genomic map of SARS-CoV-2. The number of base pairs indicates the position of various essential genomes that encode functional proteins.

Figure 2

Structure of SARS-CoV-2.

Figure 3

Mechanism of SARS-CoV-2 infection in the host cells. The SARS-CoV-2 S protein binds to the ACE2 receptor on the surface of host cells, the S1/S2 subunits are cleaved by the proprotein convertase furin. The S2’ cleavage site is exposed and further cleaved by the host cell protease transmembrane serine protease 2. Then, the viral cell entry via membrane fusion or endocytosis occurs, and RNA is released to the cytoplasm. Then, ribosomes from host cells are employed for the translation of RNA-dependent RNA polymerase before the viral RNA replication. RNA genome coding structural proteins are obtained. The structural proteins are translated into the host endoplasmic reticulum. Together with the new viral RNA and N proteins, the new virions are assembled in the ER-Golgi intermediate compartment (ERGIC) of host cells; finally, the new SARS-CoV-2 viruses are released outside the host cells through exocytosis.

Figure 4

The simplified schematic representation of antiviral immunity.

Figure 5

The impact of VOCs on the vaccine effectiveness. The summary of vaccine effectiveness is based on the Meta-analysis, the analysis (20 cohort studies with 52,782,321 participants, and 26 case–control studies with 2,584,732 cases) involves 11 vaccines (8 WHO-certified vaccines: Moderna, Pfizer, AstraZeneca, Johnson, Novavax, Sinopharm, Sinovac, Covaxin; 3 vaccines in development: SCB-2019, CVnCoV and HB02).

Figure 6

Pfizer, Moderna and AstraZeneca vaccine effectiveness against Delta (green bars) and Omicron (blue bars) variants. Short-term vaccine efficacy is marked in green/blue colour, while long-term efficacy in light green/blue colour.