COVID-19 vaccines: their effectiveness against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its emerging variants

Abstract

Background: The world has been suffering from the COVID-19 pandemic (officially declared by WHO in March 2020), caused by the severe acute respiratory β-coronavirus 2 (SARS-CoV-2) since the last week of December 2019. The disease was initially designated as a Public Health Emergency of International Concern on January 30, 2020. In order to protect the health of mass public, an array of research on drugs and vaccines against SARS-CoV-2 has been conducted globally. However, the emerging variants of SARS-CoV-2, i.e., Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) variants which evolved in late 2020 and the Omicron variant (B.1.1.529) which emerged in November 2021 along with its subvariant BA.2 which was first identified in India and South Africa in late December 2021, have raised the doubt about the efficiency of the currently used vaccines especially in terms of the consistent potential to produce neutralizing antibodies targeting the viral spike (S) protein.

Main body of the abstract: The present review discussed the functional details of major vaccines regarding their efficiency against such variants during the pandemic. Overall, the mRNA vaccines have shown around 94% effectiveness; the adenovector vaccine showed approximately 70% efficacy, whereas Sputnik V vaccines showed around 92% effectiveness; the inactivated whole-virus vaccine CoronaVac/PiCoVacc and BBIBP-CorV showed a varying effectiveness of 65-86% according to the geographic locations; the subunit vaccine NVX-CoV2373 has shown 60-89% effectiveness along with the global regions against the wild-type SARS-CoV-2 strain. However, reduced effectiveness of these vaccines against the SARS-CoV-2 variants was noticed which is suggestive for the further administration of booster dose.

Short conclusion: Maximum variants of SARS-CoV-2 emerged during the second wave of COVID-19; and extensive studies on the viral genomic sequences from all geographical locations around the world have been conducted by an array of groups to assess the possible occurrence of mutations(s) specially within the receptor binding domain of the viral spike (S) protein. Mutational similarities and the new or critical mutations within all variants have been clearly identified so far. The study of effectiveness of the currently used vaccines is also ongoing. The persistence of memory B cell action and the other immune components as well as the administration of booster dose is expected to mitigate the disease.

Keywords: COVID-19; Mutations; Neutralizing antibodies; SARS-CoV-2; Vaccine effectiveness; Vaccines; Variants.

Fig. 1

Life cycle of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the inset, the structure of SARS-CoV-2 is shown. The release of viral RNA takes place upon the viral entry, followed by the replication of viral RNA leading to the formation of subgenomic RNAs of which one category may encode the viral spike (S) protein (Drosten et al. ; Ksiazek et al. ; Noor and Maniha 2020). After translation within the ribosomes, the newly synthesized S protein migrates to the lumen of endoplasmic reticulum (ER); and new virus particles generate through budding into the lumen of the ER-Golgi intermediate compartment (ERGIC) (Kahn and McIntosh 2005). With the action of exocytosis, the virions get released; and subsequently the S protein is matured into SI and S2 subunits in the trans-Golgi network (TGN) instigated by the cellular protease, furin (Kahn and McIntosh 2005)

Fig. 2

SARS-CoV-2 spike (S) protein structure. A The binding mechanism of the host ACE-2 receptor by the SARS-CoV-2 spike (S) protein which has 1273 amino acid residues (180–200 kDa) has been shown. S protein trimers are the crown-like halo structures surrounding the viral particle. The S1 and S2 subunits form the bulbous head and stalk region (Noor and Maniha 2020). B Binding of the host ACE-2 receptor with the SARS-CoV-2 spike protein leading toward the viral fusion within the host has been shown. Indeed, different conformations of the spike (S) RBD domain in opened and closed states function in this mechanism which has been elaborately discussed by Huang et al. (2020) (not shown in this diagram). C Amino acid alignment within the SARS-CoV-2 Spike (S) protein. The S protein contains (1) the extracellular N-terminus domain (amino acids 1–13), (2) the S1 subunit (14–685 residues), and (3) the S2 subunit (686–1273 residues): the fusion peptide (FP) (788–806 residues) plus the heptapeptide repeat sequence 1 (HR1) (912–984 residues) and HR2 (1163–1213 residues); a transmembrane (TM) domain (1213–1237 residues) across the viral membrane, one region for receptor binding and one for membrane fusion; and finally, an intracellular C-terminal domain (CTD/ cytoplasm domain (1237–1273 residues) (Noor and Maniha 2020). As stated earlier, the RBD situated in the S1 subunit binds to the cell host ACE2 receptor (Kahn and McIntosh 2005). Besides, FP is actually a short segment of 15–20 conserved hydrophobic amino acid residues (mostly glycine alanine), which mediates the anchoring of the target membrane when the S protein adopts the conformation (Huang et al. 2020). Moreover, this is noteworthy that the targeting the heptad repeat (HR) has attracted the greatest interest in therapeutic drug discovery so far (Noor and Maniha 2020)

Fig. 3

SARS-CoV-2 variants of concern (VOC). The amino acid changes have been shown in all the VOC which have been compared with the genome sequence of the spike (S) protein of the original SARS-CoV-2 strain from Wuhan, China. NTD N-terminal domain, RBD receptor binding domain, FP fusion peptide domain, HR1 Heptad repeat 1, HR2 Heptad repeat 2, TM transmembrane domain, CTD C terminal domain