Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: A narrative review.

Introduction The Delta variant of SARS-CoV-2 has caused a new wave of the COVID-19 epidemic in many countries. It is the most infectious variant of SARS-CoV-2 to date, and its high infectivity means that a higher proportion of the population needs to be vaccinated to reduce the disease burden, which poses a substantial public health challenge. Areas covered The evolution of the Delta variant is reviewed, including an overview of the Delta Plus variant with a K417N mutation in the RBD, which may confer an improved immune evasion ability. Decreases in serum neutralizing antibody titers after vaccination against Delta were greater than those against Alpha but less than those against Beta. The protective efficacy of existing vaccines against the Delta variant have declined and is related to the number of doses and the time since vaccination. Expert opinion The currently used vaccines are effective against hospitalization/severe disease due to the Delta variant. Accelerating the popularization of vaccination, improving the coverage rate, and the implementation of intervention measures, such as wearing masks, are effective means to control the spread of the Delta variant and other variants. However, vaccination alone against SARS-CoV-2 without intervention measures may lead to continuous spread and the emergence of new variants.

https://www.tandfonline.com/doi/pdf/10.1080/14760584.2021.1976153

Impact of the Delta variant on vaccine efficacy and response strategies.

The current coronavirus disease 2019 (COVID-19) pandemic is the first to apply whole-genome sequencing near to real time, with over 2 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequences generated and shared through the GISAID platform. This genomic resource informed public health decision-making throughout the pandemic; it also allowed detection of mutations that might affect virulence, pathogenesis, host range or immune escape as well as the effectiveness of SARS-CoV-2 diagnostics and therapeutics. However, genotype-to-phenotype predictions cannot be performed at the rapid pace of genomic sequencing. To prepare for the next phase of the pandemic, a systematic approach is needed to link global genomic surveillance and timely assessment of the phenotypic characteristics of novel variants, which will support the development and updating of diagnostics, vaccines, therapeutics and nonpharmaceutical interventions. This Review summarizes the current knowledge on key viral mutations and variants and looks to the next phase of surveillance of the evolving pandemic.

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The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology.

The effectiveness of BNT162b2, ChAdOx1, and mRNA-1273 vaccines against new SARS-CoV-2 infections requires continuous re-evaluation, given the increasingly dominant Delta variant. We investigated the effectiveness of the vaccines in a large community-based survey of randomly selected households across the UK. We found that the effectiveness of BNT162b2 and ChAd0x1 against any infections (new PCR positives) and infections with symptoms or high viral burden is reduced with the Delta variant. A single dose of the mRNA-1273 vaccine had similar or greater effectiveness compared to a single dose of BNT162b2 or ChAdOx1. Effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity following second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positives but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher among those vaccinated following a prior infection and younger adults. With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.

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Impact of Delta on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

Importance Randomized clinical trials have shown that the COVID-19 vaccines currently approved in the US are highly efficacious. However, more evidence is needed to understand the population-level impact of the US vaccination rollout in the face of the changing landscape of COVID-19 pandemic in the US, including variants with higher transmissibility and immune escape. Objective To quantify the population-level impact of the US vaccination campaign in averting cases, hospitalizations and deaths from December 12, 2020 to June 28, 2021. Design Age-stratified agent-based model which included transmission dynamics of the Alpha, Gamma and Delta variants in addition to the original Wuhan-1 variant. Setting Our model was calibrated to COVID-19 outbreak and vaccine rollout in the US. Model predictions were made at the country level. Participants Simulated age-stratified population representing US demographics. Main Outcomes and Measures Cases, hospitalizations and deaths averted by vaccination against COVID-19 in the US, compared to the counterfactuals of no vaccination and vaccination administered at half the actual pace. Results The swift vaccine rollout in the US curbed a potential resurgence of cases in April 2021, which would have been otherwise fuelled by the Alpha variant. Compared to the scenario without vaccines, we estimated that the actual vaccination program averted more than 26 million cases, 1.2 million hospitalizations and saved 279,000 lives. A vaccination campaign with half the actual rollout rate would have led to an additional 460,000 hospitalizations and 121,000 deaths. Conclusions and Relevance The COVID-19 vaccination campaign in the US has had an extraordinary impact on reducing disease burden despite the emergence of highly transmissible variants. These findings highlight that the pace of vaccination was essential for mitigating COVID-19 in the US, and underscore the urgent need to close the vaccine coverage gaps in communities across the country. Key Points Question How effective was the United States (US) vaccination campaign in suppressing COVID-19 burden? Findings The vaccination campaign was highly effective in curbing the COVID-19 outbreak in the US. We estimated that the vaccine rollout saved over 275,000 lives and averted 1.2 million hospitalizations. Meaning The swift vaccine rollout in the US averted a remarkable number of cases, hospitalizations and deaths despite the emergence of highly transmissible variants.

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COVID-19 deaths and hospitalizations averted by rapid vaccination rollout in the United States

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

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Jon Perkins

Papers

Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination