https://orcid.org/0000-0002-8526-6013
ABSTRACT
The circulating variants of SARS-CoV-2 pose a threat to the public health response worldwide, especially in the case of developing countries, lacking vaccines and having compromised health-care facilities. This article highlights several recent studies conducted to determine the efficacy of COVID-19 vaccines against variants of concern. These studies comprise clinical trials and neutralization assay-based studies conducted on messenger RNA (mRNA), recombinant, viral vector-based, and inactivated vaccines.
The Delta variant, also known as B.1.617.2, has a viral lineage initially detected in India in April and May 2021 after widespread infections in the community. According to the data provided by Our World in Data, nearly half of the world's population has received at least one dose of a COVID-19 vaccine, with billions of doses administered globally.Citation1 In India, over half-billion doses have been administered. In several regions of the country, the lineage spread quickly and exhibited evidence of partial vaccine resistance. However, researchers have found it challenging to separate the variant’s inherent features from other circumstances that contributed to India’s confirmed cases. The characteristic mutations in the spike protein of B.1.617.2 variant are T19R, Δ157-158, L452R, T478K, D614G, P681R, and D950N.Citation2,Citation3 Several of these mutations may influence immune responses aimed toward the key antigenic areas (452 and 478) of the receptor-binding protein and the deletion of a portion of the N terminal domain.Citation4 P681R is located at the S1/S2 cleavage site, and studies have shown that strains with mutations at this location have greater replication, resulting in larger viral loads and transmission.Citation5
The resurgence of COVID-19 cases in the UK has provided scientists with a clear picture of the threat of the Delta variant. Delta has been reported to be around 40% more transmissible than the already highly infectious Alpha variant (also called B.1.1.7), which was identified in the UK in late 2020. According to a Public Health England study, a single dosage of AstraZeneca’s vaccination reduced a person’s risk of having COVID-19 symptoms caused by the Delta variant by 32.9%, compared to 51.4% for the Alpha variant.Citation6,Citation7 Similarly, for Pfizer, the corresponding percentages are 33.2% and 49.2%, respectively. A second dose of the AstraZeneca vaccine increased protection against Delta to 59.8% (compared to 66.1% against Alpha), while two doses of Pfizer’s vaccine increased protection against Delta to 87.9% (compared to 93.4% against Alpha). Hence, after two doses of vaccination of either Pfizer-BioNTech’s BNT162b2 or AstraZeneca’s ChAdOx1, the differences in vaccine effectiveness were modestly lower for the B.1.617.2 variant as compared to the B.1.1.7 variant ().
Table 1. Comparison of vaccine effectiveness in preventing symptomatic SARS-CoV-2 infection confirmed by RT-PCR
Another Public Health England study related to the Delta variant has found that people who receive their first dose of any of the Pfizer or AstraZeneca vaccines are 75% less likely to undergo hospitalization than unvaccinated individuals.Citation6 This number increases to 94% for fully vaccinated individuals. A recent study released on June 25, 2021, shows that the vaccine effectiveness with one dose is 80% while with two doses is 96% against the Delta variant for protection from hospitalization.Citation8 Similarly, for the Beta variant (B.1.351) first detected in South Africa in October 2020, clinical studies conducted by the US biotech companies like Novavax, Johnson & Johnson, and UK’s AstraZeneca have confirmed a decreased efficacy. Specifically, Novavax clinical trials have demonstrated 89.3% efficacy in the UK (cohort of roughly 15,000 people) for their recombinant protein vaccine (NVX-CoV2373).Citation9
In the phase 2a-b Novavax trial conducted in South Africa, HIV-negative patients (total 4160) had a vaccine efficacy of 60.1%. Post hoc vaccine efficacy among the HIV-negative participants against the B.1.351 variant was 51.0%.Citation10 The clinical trials conducted by Johnson and Johnson’s have shown that the protection level against moderate-to-severe COVID-19 infection is 72% in the US, 66% in Latin America, and 57% in South Africa, 28 days post-vaccination for their human adenovirus-based vaccine.Citation11 The neutralizing activity of Ad26.COV2.S COVID‐19 vaccine in sera from phase 3 trial participants against the Beta (B.1.351) and Gamma (P.1) variants was 5.0 and 3.3 times lower, respectively, as compared to the Wuhan-Hu-1 (WA1/2020 variant).Citation12 In comparison to the B.1 strain having D614G mutation, the reduction in Ad26.COV2.S induced neutralization was most pronounced in the Beta (B.1.351) and Gamma (P.1) variants; 3.6-fold and 3.4-fold, respectively. While in the case of Delta variant (B.1.617.2), 1.6-fold reduction was observed.
Recently, Moderna performed neutralization assays on the emerging variants and Variants of concern (VOC) and observed a modest reduction in neutralization titers against the Delta (2.1-fold), Gamma (P.1, 3.2-fold), Kappa (B.1.617.1, 3.3–3.4-fold), and Eta (B.1.525, 4.2-fold) variants relative to those against the ancestral (D614G) strain.Citation13 Serum samples from eight individuals were collected in 1 week following the second dose of the primary series in phase 1 clinical trial of the Moderna COVID-19 Vaccine (mRNA-1273) for this study. A study conducted in Qatar has reported that the mRNA-1273 vaccine was 88.1% effective 14 or more days after the first dose and 100% effective 14 or more days after the second dose against B.1.1.7 variant.Citation14 Similarly, against the B.1.351 variant, the analogous vaccine effectiveness was 61.3% after the first dose and 96.4% after the second dose. After the first and second doses, the vaccine’s efficacy against any severe, critical, or fatal COVID-19 disease caused by any SARS-CoV-2 infection (predominantly B.1.1.7 and B.1.351) was 81.6% and 95.7%, respectively.
A recent study in Nature shows that there is barely any inhibition of Delta variant by sera from individuals who have received one dose of Pfizer or AstraZeneca vaccinesCitation15. During administration of two doses, the vaccines generated neutralization response in 95% of the individuals with titers 3-to-5-fold lower against Delta than Alpha. The phase 3 trials of Bharat Biotech’s COVAXIN (BBV152) and the related efficacy data have shown that the overall efficacy of COVAXIN is 77.8%, with 93.4% effectiveness against severe COVID-19 and 65.2% protection against the Delta variant.Citation16
At the end of July, a third (booster) dose of the Pfizer-BioNTech mRNA vaccine was approved in Israel. Approval was granted for people aged 60 years or above who had received a second dose of vaccine at least 5 months earlier. According to the data published in a recent study in September, the rate of confirmed infection in the booster group was 11.3 times lower than in the non-booster group at least 12 days after the booster dose.Citation17 There was a significant reduction in the rate of severe illness by COVID-19 (by a factor of 19.5) compared to people who had received only two jabs and were studied during a similar period. The results are of prime importance, considering that over half of Israel’s adult population has received the booster dose.
The recent data provided by vaccine manufacturers and independent researchers support the claim that COVID-19 variants can considerably affect the effectiveness of vaccines. Although the vaccine effectiveness has been reduced due to the circulating variants, they are still our best hope to prevent the emergence of variants that might significantly challenge the vaccines in the upcoming future.
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References
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