The effect of SARS-CoV-2 variants on the efficacy of COVID-19 vaccines
The effect of SARS-CoV-2 variants on the efficacy of COVID-19 vaccines
Mohammad Shayestehpour,1,*Mehrdad Mohammadi,2
1. Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, I.R. Iran 2. Department of Microbiology and Immunology, Faculty of Medicine, Kashan University of Medical Sciences, Kashan, I.R. Iran
Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a novel viral agent that can cause a life-threatening respiratory disorder named coronavirus disease 2019 (COVID‑19). Several protein subunit COVID-19 vaccines have been proposed for use in humans. The major concern is the efficacy of subunit vaccines and elicited antibodies to neutralize the different SARS-CoV-2 variants. This review is focused on the impact of spike mutated variants of SARS-CoV-2 (B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma), B.1.617 (Delta) and C.37 (Lambda) on the efficacy of subunit recombinant vaccines.
Methods: Independent searches in PubMed, Web of Science, Scopus, and Global Index Medicus were conducted by two researchers. The search strategy consisted of a word combination covering the following areas (COVID-19 OR SARS-CoV-2) AND Vaccine AND B.1.1.7 Variant OR B.1.351 variant OR B.1.1.28.1 Variant OR B.1.617.2 OR C.37 variant. The search had no geographic or language restrictions and included all studies reporting on efficacy of SARS-CoV-2 vaccines against variants Alpha, Beta, Gamma, Delta, and Lambda.
Results: Xiu et al. revealed that UK and Brazil variants have no significantly decreased effect on vaccine impact and neutralization by sera from vaccinated individuals after two doses of BNT162b2 (Pfizer). SARS-CoV-2 vaccine NVX-CoV2373, produced by Novavax is based on S protein derived from the SARS-CoV-2 Wuhan reference strain, has shown 85.6% efficacy against the B.1.1.7 variant (95.6% against the original strain). However, in a study in South Africa Callaway et al. reported a 49.4% efficacy against B.1.351 variant in the overall population. These interim data evidence a significant decrease in vaccine efficacy influenced by variants such as B.1.351. In a study, B.1.1.7 remained sensitive to neutralization, albeit at moderately reduced levels, by serum samples from convalescent individuals and recipients of an mRNA vaccine (Moderna) and a protein nanoparticle vaccine (NVXCoV2373, Novavax). Wu et al. found no considerable impact in the neutralizing potency of sera from people who received the Moderna vaccine against the B.1.1.7 variant. Nevertheless, Wang et al. reported that B.1.351 variant was particularly more resistant to neutralization in people immunized with Pfizer or Moderna vaccines. Wilfredo et al. analyzed neutralization potency in individuals who received one or two doses of either BNT162b2 or mRNA-1273 vaccines, suggesting that a relatively small number of mutations, like B.1.351 can mediate potent escape from vaccine responses. Shinde et al. reported on a comprehensive analysis of the NVX-CoV2373 vaccine in 4387 participants. They revealed that efficacy against B.1.351 was 51.0%. Mlcochova et al. showed evasion of the Delta variant from neutralizing antibodies present in convalescent patients, as well as in vaccinated individuals with two different vaccines in the UK (adenovirus vector (ChAdOx-1), and the other mRNA 19 (BNT162b2)). They demonstrated a reduced susceptibility of Delta to vaccine-elicited neutralization. In their data, the variant showed approximately 8 to 20-fold reduced sensitivity to vaccine-elicited antibodies. In another report by Davis et al., reductions in the neutralization of B.1.617.1 and B.1.617.2 were 4.31- and 5.11-fold, respectively. In another report, Lustig and et al. demonstrated significant fold change reduction in neutralizing titers: Gamma (P.1) 2.3, Beta (B.1.351) 10.4, Delta 2.1, and Lambda 2.6. The fold reduction of the Alpha (B.1.1.7) variant was not significant. Acevedo et al. observed greater infectivity mediated by the Lambda spike protein compared to D614G (lineage B) or Alpha and Gamma variants. In addition, neutralization was reduced by 3.05-fold for the Lambda variant, 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant. Tada et al. showed an average 2.3-3.3-fold reduction of antibody titers against Lambda variant.
Conclusion: Subunit vaccines with strong immunogenic capacity can efficiently elicit host immune response. However, the major healthcare concern is a reduction of subunit vaccines efficacy in translated by lower antibody neutralization potency against SARS-CoV-2 Alpha, Beta, Gamma, Delta, and Lambda variants. To date, low or no significant impact on vaccine efficacy against Alpha variants has been reported. Concern about and Delta, Beta, Gamma, and Lambda mutations on vaccine efficacy and treatments is greater than for the Alpha variant.