Effectiveness of COVID-19 Vaccines against Delta (B.1.617.2) Variant: Comparison
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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][3][4][5] and real-world evidence [6,7,8,9][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][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 [37,38,39][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 [29][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 [40,41,42,43,44][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 [45][30]. The L452R and T478K mutations have been associated with increased transmissibility of the Delta variant [46][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% [39][23]. A similar finding of lower pooled VE against Delta, Beta, and Gamma compared to Alpha was reported by other studies [47,48][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 [47][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 [49][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 [50][35]. Another report supported the higher VE of the mRNA vaccines against Variants of Concern, including Delta [48][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 [51][36]. For example, the Pfizer-BioNTech vaccine, which had 95% efficacy in the primary multinational clinical trial [52][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 [52][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 [36][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 [53][39]. It is plausible that for the Delta variant with a reproduction number range of 3.2 to 8 [54][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.  

References

  1. Outbreak.info. Available online: https://outbreak.info/ (accessed on 14 November 2021).
  2. World Health Organization. COVID-19 Vaccines WHO EUL Issued. Available online: https://extranet.who.int/pqweb/vaccines/vaccinescovid-19-vaccine-eul-issued (accessed on 14 November 2021).
  3. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 2021, 384, 403–416.
  4. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N. Engl. J. Med. 2020, 383, 2603–2615.
  5. Voysey, M.; Clemens, S.A.C.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Bijker, E. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet 2021, 397, 99–111.
  6. Dagan, N.; Barda, N.; Kepten, E.; Miron, O.; Perchik, S.; Katz, M.A. BNT162b2 mRNA COVID-19 caccine in a nationwide mass vaccination setting. N. Engl. J. Med. 2021, 384, 1412–1423.
  7. Hall, V.J.; Foulkes, S.; Saei, A.; Andrews, N.; Oguti, B.; Charlett, A.; Wellington, E.; Stowe, J.; Gillson, N.; Cowley, A.; et al. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): A prospective, multicentre, cohort study. Lancet 2021, 397, 1725–1735.
  8. Lopez Bernal, J.; Andrews, N.; Gower, C.; Robertson, C.; Stowe, J.; Tessier, E. Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study. BMJ 2021, 373, n1088.
  9. Shrotri, M.; Krutikov, M.; Palmer, T.; Giddings, R.; Azmi, B.; Subbarao, S. Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities in England (VIVALDI): A prospective cohort study. Lancet Infect. Dis. 2021, 21, 1529–1538.
  10. Updates on COVID-19 Variants of Concern. Available online: https://nccid.ca/covid-19-variants/ (accessed on 10 December 2021).
  11. Konings, F.; Perkins, M.D.; Kuhn, J.H.; Pallen, M.J.; Alm, E.J.; Archer, B.N. SARS-CoV-2 variants of interest and concern naming scheme conducive for global discourse. Nat. Microbiol. 2021, 6, 821–823.
  12. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern. Available online: https://www.cdc.gov/coronavirus/2019-ncov/variants/omicron-variant.html (accessed on 26 November 2021).
  13. Dai, L.; Gao, G.F. Viral targets for vaccines against COVID-19. Nat. Rev. Immunol. 2021, 21, 73–82.
  14. Letko, M.; Marzi, A.; Munster, V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat. Microbiol. 2020, 5, 562–569.
  15. Elena, S.F.; Sanjuán, R. Adaptive value of high mutation rates of RNA viruses: Separating causes from consequences. J. Virol. 2005, 79, 11555–11558.
  16. Li, Q.; Wu, J.; Nie, J.; Zhang, L.; Hao, H.; Liu, S. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. Cell 2020, 182, 1284–1294.
  17. Jia, Z.; Gong, W. Will mutations in the spike protein of SARS-CoV-2 lead to the failure of COVID-19 vaccines? J. Korean Med. Sci. 2021, 36, e124.
  18. Chen, X.; Wang, W.; Chen, X.; Wu, Q.; Sun, R.; Ge, S. Prediction of long-term kinetics of vaccine-elicited neutralizing antibody and time-varying vaccine-specific efficacy against the SARS-CoV-2 Delta variant by clinical endpoint. medRxiv 2021.
  19. Public Health England. SARS-CoV-2 Variants of Concern and Variants under Investigation in England. Technical Briefing 11. SARS-CoV-2 Variants of Concern and Variants under Investigation in England. Available online: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/986380/Variants_of_Concern_VOC_Technical_Briefing_11_England.pdf (accessed on 13 May 2021).
  20. Lopez Bernal, J.; Andrews, N.; Gower, C.; Gallagher, E.; Simmons, R.; Thelwall, S. Effectiveness of COVID-19 vaccines against the B.1.617.2 (Delta) variant. N. Engl. J. Med. 2021, 385, 585–594.
  21. Shah, S.M.; Alsaab, H.O.; Rawas-Qalaji, M.M.; Uddin, M.N. A review on current COVID-19 vaccines and evaluation of particulate vaccine delivery systems. Vaccines 2021, 9, 1086.
  22. Milken Institute. COVID-19 Treatment and Vaccination Trackers. 2021. Available online: https://covid-19tracker.milkeninstitute.org/#vaccines_intro (accessed on 14 December 2021).
  23. Liu, Q.; Qin, C.; Liu, M.; Liu, J. Effectiveness and safety of SARS-CoV-2 vaccine in real-world studies: A systematic review and meta-analysis. Infect. Dis. Poverty 2021, 10, 1–15.
  24. Sheikh, A.; McMenamin, J.; Taylor, B.; Robertson, C. SARS-CoV-2 Delta VOC in Scotland: Demographics, risk of hospital admission, and vaccine effectiveness. Lancet 2021, 397, 2461–2462.
  25. Puranik, A.; Lenehan, P.J.; Silvert, E.; Niesen, M.J.; Corchado-Garcia, J.; O’Horo, J.C. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of Alpha and Delta variant prevalence. medRxiv 2021.
  26. Nanduri, S.; Pilishvili, T.; Derado, G.; Soe, M.M.; Dollard, P.; Wu, H. Effectiveness of Pfizer-BioNTech and Moderna vaccines in preventing SARS-CoV-2 infection among nursing home residents before and during widespread circulation of the SARS-CoV-2 B. 1.617. 2 (Delta) variant—National Healthcare Safety Network, March 1–August 1, 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 1163.
  27. Rosenberg, E.S.; Holtgrave, D.R.; Dorabawila, V.; Conroy, M.; Greene, D.; Lutterloh, E. New COVID-19 cases and hospitalizations among adults, by vaccination status—New York, May 3–July 25, 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 1306.
  28. Tang, P.; Hasan, M.R.; Chemaitelly, H.; Yassine, H.M.; Benslimane, F.; Al Khatib, H.A. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the Delta (B. 1.617. 2) variant in Qatar. medRxiv 2021.
  29. Herlihy, R.; Bamberg, W.; Burakoff, A.; Alden, N.; Severson, R.; Bush, E.; Rapid increase in circulation of the SARS-CoV-2, B. 1.617. 2 (Delta) variant—Mesa County, Colorado, April–June 2021. Morb. Mortal. Wkly. Rep. 2021, 70, 1084.
  30. Deng, X.; Garcia-Knight, M.A.; Khalid, M.M.; Servellita, V.; Wang, C.; Morris, M.K. Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. medRxiv 2021.
  31. Adam, D. What Scientists Know about New, Fast-Spreading Coronavirus Variants. 2021. Available online: https://www.nature.com/articles/d41586-021-01390-4 (accessed on 14 December 2021).
  32. Harder, T.; Külper-Schiek, W.; Reda, S.; Treskova-Schwarzbach, M.; Koch, J.; Vygen-Bonnet, S. Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B. 1.617. 2) variant: Second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021. Eurosurveillance 2021, 26, 2100920.
  33. Zeng, B.; Gao, L.; Zhou, Q.; Yu, K.; Sun, F. Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: A systematic review and meta-analysis. medRxiv 2021.
  34. World Health Organization. WHO Target Product Profiles for COVID-19 Vaccines. Available online: https://www.who.int/publications/m/item/who-target-product-profiles-for-covid-19-vaccines (accessed on 14 December 2021).
  35. Pormohammad, A.; Zarei, M.; Ghorbani, S.; Mohammadi, M.; Razizadeh, M.H.; Turner, D.L. Efficacy and safety of COVID-19 vaccines: A systematic review and meta-analysis of randomized clinical trials. Vaccines 2021, 9, 467.
  36. Zimmermann, P.; Curtis, N. Factors that influence the immune response to vaccination. Clin. Microbiol. Rev. 2019, 32, e00084-18.
  37. Moustsen-Helms, I.R.; Emborg, H.-D.; Nielsen, J.; Nielsen, K.F.; Krause, T.G.; Molbak, K. Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 vaccine in long-term care facility residents and healthcare workers—A Danish cohort study. medRxiv 2021.
  38. Tartof, S.Y.; Slezak, J.M.; Fischer, H.; Hong, V.; Ackerson, B.K.; Ranasinghe, O.N. Effectiveness of mRNA BNT162b2 COVID-19 vaccine up to 6 months in a large integrated health system in the USA: A retrospective cohort study. Lancet 2021, 398, 1407–1416.
  39. Bartsch, S.M.; O’Shea, K.J.; Ferguson, M.C.; Bottazzi, M.E.; Wedlock, P.T.; Strych, U. Vaccine efficacy needed for a COVID-19 coronavirus vaccine to prevent or stop an epidemic as the sole intervention. Am. J. Prev. Med. 2020, 59, 493–503.
  40. Liu, Y.; Rocklöv, J. The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus. J. Travel Med. 2021, 28.
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