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Turner, R. Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant. Encyclopedia. Available online: (accessed on 10 December 2023).
Turner R. Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant. Encyclopedia. Available at: Accessed December 10, 2023.
Turner, Raymond. "Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant" Encyclopedia, (accessed December 10, 2023).
Turner, R.(2021, December 30). Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant. In Encyclopedia.
Turner, Raymond. "Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant." Encyclopedia. Web. 30 December, 2021.
Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant

The high transmissibility, mortality, and morbidity rate of the SARS-CoV-2 Delta (B.1.617.2) variant have raised concerns regarding vaccine effectiveness (VE). The short-term effectiveness of the Pfizer-BioNTech, Moderna, AstraZeneca, Bharat Biotech, and CoronaVac vaccines for the prevention of infection and the reduction in the severity of illness and hospitalizations associated with the Delta variant are supported. 

COVID-19 SARS-CoV-2 SARS-CoV-2 variants SARS-CoV-2 B.1.617.2 variant vaccines Covid-19 Delta variant

1. Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 82 million known cases by the end of 2020 [1]. To prevent the spread of COVID-19, significant progress has been achieved in developing several COVID-19 vaccines to reduce the rate of transmission, the severity of the disease, symptom development, and hospitalizations and increase the recovery rate [2]. This has been demonstrated by clinical trials [3][4][5] and real-world evidence [6][7][8][9]. However, the emergence of new variants, especially those related to the spike gene function, threatens the efficacy of current vaccines [10]. New variants that acquire genomic mutations leading to enhanced transmission, immune system evasion, and/or pathogenicity have been classified as Variants of Concern (VOCs). The World Health Organization (WHO) reported the main SARS-CoV-2 VOCs along with the country of the first detection and the date of designation including the Alpha variant (B.1.1.7) in the United Kingdom on 18 December 2020, the Beta variant (B.1.351) in South Africa on 18 December 2020, the Gamma variant (P.1) in Brazil on 11 January 2021, the Delta variant (B.1.617.2) in India on 11 May 2021 [11], and the most recent variant, Omicron (B.1.1.529), in South Africa on 26 November 2021 [11][12][13].
The spike (S) protein, which is the principal target in COVID-19 vaccines [13], is one of the five structural proteins of SARS-CoV-2 that has two different subunits. The S1 subunit, which contains the receptor-binding domain, mediates attachment to the cell surface receptors used by SARS-CoV-2, mainly the angiotensin-converting enzyme 2. The S2 subunit is responsible for the membrane fusion that is necessary for the viral entry into the host cell [14]. As with other RNA viruses, SARS-CoV-2 benefits from a high mutation rate, resulting in extensive adaptability [15]. Mutations in the receptor-binding domain of the S protein seem to have a crucial impact on the infectivity, immune reaction, and pathogenicity of the virus [16]. Since the new variants of SARS-CoV-2 have multiple mutations including those in the S protein, there is a concern whether the mutations might change the antigenicity of the virus and subsequently the effectiveness of vaccines [17].
The Delta variant, one of the VOCs, caused a significant surge in COVID-19 cases in India, reaching over 400,000 daily new cases and 4000 daily new deaths by May 2021 [18]. Moreover, this variant was reported in 43 countries simultaneously, including drastic surge cases in the United Kingdom, mostly linked with travelling from India and community transmission [19], which created concern since the effectiveness of the existing vaccines against this variant was unclear [20].
Recently, the new VOC, named Omicron by the WHO, has raised public fears, and as suggested by preliminary evidence, it has increased the risk of breakthrough infections [12]. The question of whether vaccination is effective against Omicron needs more data. Yet, Delta is the dominant variant in many countries [12].

2. Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant

Several vaccines have been authorized for SARS-CoV-2, and the development of new vaccines is ongoing [21][22][23]. However, the recurrent appearance of new variants of SARS-CoV-2 has raised concern regarding the VE against all variants. The Delta variant with increased transmissibility and more severe infections first appeared in India and replaced the previously circulating variants, even in areas considered to have high vaccination rates for eligible individuals 18 years and older [24]. An increased incidence of SARS-CoV-2 infection at the time of the Delta variant’s predominance has been suspected to be associated with the decreased effectiveness of vaccines against Delta [25][26][27][28][29].
The Delta variant (B.1.617.2), similar to other new variants of SARS-CoV-2, has developed multiple mutations primarily in the S protein, such as L452R. The L452R mutation, which is in the receptor-binding domain of the S1 subunit, can prevent the binding of the neutralizing antibodies to the virus and decrease the efficacy of vaccine-induced antibodies [30]. The L452R and T478K mutations have been associated with increased transmissibility of the Delta variant [31].
Studies showed 53.8% overall VE after the first dose that increased to a level of 81.9% after the second dose. The large difference between overall VE after the first and second doses supports having a full vaccination course for optimal VE. A study reported a pooled VE for the prevention of SARS-CoV-2 of 41% after the first dose and 85% after the second dose. They also reported the pooled VE for the prevention of SARS-CoV-2 VOCs, which was 74% for the Delta variant, the highest for the Alpha variant at 85%, 75% for the Beta variant, and the lowest for the Gamma variant at 54% [23]. A similar finding of lower pooled VE against Delta, Beta, and Gamma compared to Alpha was reported by other studies [32][33]. It was also noted that higher VE against Alpha compared to Delta was only present in preventing mild infection, but when the endpoint was severe COVID-19, the efficacy was the same [32].
The highest VE occurred after a full vaccination course, with two mRNA-based vaccines having a VE of 83.7% (Pfizer/BioNTech) and 77.5% (Moderna), and the vector vaccine AstraZeneca having a VE of 80%. According to the WHO Target Product Profiles for COVID-19 Vaccines, a “Clear demonstration of efficacy (on a population basis) ideally with ~50% point estimate” has been recommended as a minimum measure for VE [34], which shows that all five vaccines in this study have acceptable VE to prevent the SARS-CoV-2 Delta variant. The high VE reported after the first dose of Moderna (72%) may be important to decrease the risk of infection during the time between doses. Although the two inactivated virus-based vaccines showed lower VE, in light of the high infectivity and severity of infection with Delta, even a VE of 65% for Bharat Biotech and 59% for CoronaVac in our results would decrease the disease burden.
Reports on other types of vaccines were scarce, which necessitates an urgent need to study the effectiveness of other vaccines against the Delta variant. Only one study reported the VE after a third dose, which was about 97% for Pfizer-BioNTech and Moderna and 64% for CoronaVac, with higher titers of neutralizing antibodies compared to the primary doses [18]. With regard to VE against Delta-associated complications including severe infection or death, this study shows that Pfizer-BioNTech, Moderna, and AstraZeneca have about 90% VE after the second dose. VE against hospitalization was also high for Pfizer-BioNTech (93%) and AstraZeneca (88%). A meta-analysis study of phase II/III clinical trials before the emergence of the Delta variant reported an overall 95% vaccine efficacy for mRNA-based vaccines, higher than that reported in our study, and they reported 80% vaccine efficacy for viral vector vaccines, equal to this study [35]. Another report supported the higher VE of the mRNA vaccines against Variants of Concern, including Delta [33].
In addition to supporting the acceptable effectiveness of COVID-19 vaccines against the Delta variant, this study also shows different levels of VE, from 83.7% for Pfizer/BioNTech to 59% for CoronaVac. The difference may have partially originated from the different numbers of cases that were included for each vaccine. However, responsiveness to vaccines depends on multiple hosts and environmental factors such as age, gender, co-morbidities, and season, in addition to vaccination factors and the time after vaccination [36]. For example, the Pfizer-BioNTech vaccine, which had 95% efficacy in the primary multinational clinical trial [37], was reported to have a 64% and 90% VE after seven days of the second dose in two Danish populations, a group of residents of long-term care facilities and a group of healthcare workers, respectively [37]. Such information leads one to appreciate that there are multiple factors including side effect risks of various vaccine formulations in addition to a given VE.
It has been reported that after 6–8 months, the effectiveness of Moderna and Pfizer-BioNTech decreased, but a third dose markedly increased the efficacy against the Delta variant [18]. A retrospective cohort study reported that the VE for Pfizer-BioNTech was high for both Delta and non-Delta variants, but it decreased after the 4–5-month follow-up. However, the VE for this vaccine against hospitalization was high for Delta and non-Delta variants up to six months [38].
The population vaccination rate is another challenge associated with the COVID-19 waves after the emergence of the new variants. A computational model of VE necessary for the elimination of the COVID-19 pandemic showed that with a VE of 80% when the reproduction number (R0) of the virus is 2.5, the population vaccination rate should be 60%. With the same VE, when the R0 increases to 3.5, the vaccination rate should be 75% at a minimum [39]. It is plausible that for the Delta variant with a reproduction number range of 3.2 to 8 [40], the population vaccination rate has to significantly exceed 75%. Population vaccination rates to date are just beginning to include children, which affects overall herd immunity, and the ongoing transmission of the virus in all unvaccinated cohorts.
Early anecdotal data suggest mRNA-based vaccines are around 30–40% effective at preventing infections and 70% effective at preventing severe disease. This may be due to the timing of the onset where most people are approaching 6 months since their second dose, leading to waning immunity. This is now influencing governments towards recommending a third booster dose to control this hypervirulent VOC.


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