B.1.617.2(デルタ株)に対するワクチン接種の比較評価

//Background//---
In the United Kingdom, the number of new SARS-CoV-2 infection is 47,599 in 19/July, 2021 according to JHU CSSE COVID-19 Data. In this country, B.1.617.2 (delta) variant mainly emerged in India in December 2020 has been largely confirmed due to travel from India and with community infection(2). Probably, the infection wave from early June, 2021 in U.K may mainly include this variant.
 Jamie Lopez Bernal, Nick Andrews report the epidemiological data on two vaccine efficacy against infection in a comparative way of B.1.1.7 (Alpha variant) and B.1.617.2 (Delta variant)(1). I want to share a part of this important report with the global readers.
 
//B.1.617.2 delta variant//---
*Spike protein mutations: T19R, Δ157-158, L452R, T478K, D614G, P681R and D950N 1
*Key antigenic binding domain to ACE2 receptor: 452(L452R), 478(L478).
These mutations could elevate infectivity to cell besides D614G.
*P681R is at the S1-S2 cleavage site associated to endocytosis into cell, leading to high infectivity(3).
*Therefore, B.1.617.2 could have high replication rate through high cell infectivity, so it threatens to rapidly make community transmission.
 
//Evaluate Condition(1)//---
*Vaccine: BNT162b2(Pfizer/BioNTech), ChAdOx1 nCoV-19 (AstraZeneca)
*Nation: England
*Collected Data: From October 26, 2020 to May 16, 2021
*Age: 16 years and older than it
*Total: 19,109 participants
*Alpha variant: 14,873 / Delta variant: 4272 -- PCR positive
*Interval from dose 1 to dose 2: about 55 days and 85 days (See Figure S2)
Therefore, interval is longer than general protocol (21 days).
*PCR conduction criteria: high temperature, new continuous cough, loss or change in sense of smell or taste
 
//Result(1)(See Table 2)//---
Total / PCR-positive / infection rate -- in this order
(Alpha variant)
*Unvaccinated: 96,371 / 7,313 / 0.076
*BNT162b2 vaccine Dose 1(partly vaccinated):
8,641 / 450 / 0.052 Efficacy: 47.5%
*BNT162b2 vaccine Dose 2(fully vaccinated):
15,749 / 49 / 0.003 Efficacy: 93.7%
* ChAdOx1 nCoV-19 vaccine Dose 1(partly vaccinated):
42,829 / 1776 / 0.041 Efficacy: 48.7%
*ChAdOx1 nCoV-19 vaccine Dose 2: (fully vaccinated)
8,244 / 94 / 0.011 Efficacy: 74.5%
-
(Delta variant)
*Unvaccinated: 96,371 / 4,043 / 0.042
*BNT162b2 vaccine Dose 1(partly vaccinated):
8,641 / 137 / 0.016 Efficacy: 35.6%
*BNT162b2 vaccine Dose 2(fully vaccinated):
15,749 / 122 / 0.008 Efficacy: 88.0%
* ChAdOx1 nCoV-19 vaccine Dose 1(partly vaccinated):
42,829 / 1356 / 0.032 Efficacy: 30.0%
*ChAdOx1 nCoV-19 vaccine Dose 2: (fully vaccinated)
8,244 / 218 / 0.026 Efficacy: 67.0%
 
//Conclusion(1)//---
*Fully vaccination (2 times dose) is needed to prevent infection owing to significant improvement vaccine efficacy compared to unvaccinated and Dose 1 groups.
*BNT162b2 vaccine is relatively higher than ChAdOx1 nCoV-19 vaccine in prevention in 2 times dose condition.
 
//Discussion//---
*The data on the admission number to a hospital with moderate-to-severe symptomatic case is needed for evaluation of social risk against B.1.617.2 variant. Vaccine have been found to be highly efficacious against symptomatic disease necessary to admission in clinical trials(4-6) and epidemiologically(7-11). However, to my knowledge, efficacy rate against moderate-to-severe symptomatic case exclusively on B.1.617.2 (delta) variant has not been officially published. Therefore, the epidemiological data against these symptomatic case on this variant is socially needed.
*Vaccination is epidemiologically effectives even in current spreading Delta variant, so herd immunity owing to high vaccination rate, but not hesitancy is socially important. Therefore, polite communication between medicine, government and citizen based on scientific data including safety issue (i.e. side effect) is needed to elevate vaccination rate.
 
//Support(1)//---
Supported by Public Health England (PHE). The Covid-19 Genomics U.K. Consortium (COG-UK) is supported by funding from the Medical Research Council part of U.K. Research and Innovation, the National Institute of Health Research, and Genome Research, operating as the Wellcome Sanger Institute.
 
//Special note on ethics//---
Surveillance of coronavirus disease 2019 (Covid-19) testing and vaccination is undertaken under Regulation 3 of the Health Service (Control of Patient Information) Regulations 2002 to collect confidential patient information (www.legislation.gov.uk/uksi/2002/1438/regulation/3/made. opens in new tab) under Sections 3(i) (a) to (c), 3(i)(d) (i) and (ii), and 3. The study protocol was subject to an internal review by the Public Health England Research Ethics and Governance Group and was found to be fully compliant with all regulatory requirements. Given that no regulatory issues were identified and that ethics review is not a requirement for this type of work, it was decided that a full ethics review would not be necessary.
 
//Acknowledgement(1)//---
We thank the members of the PHE Covid-19 Data Science Team, the PHE Outbreak Surveillance Team, NHS England, NHS Digital, and NHS Test and Trace for their roles in developing and managing the testing for severe acute respiratory coronavirus 2 (SARS-CoV-2), variant identification and vaccination systems, and data sets, as well as the reporting NHS vaccinators and the staff of the NHS laboratories, PHE laboratories, and lighthouse laboratories; the staff of the Wellcome Sanger Institute and other laboratories that were involved in whole-genome sequencing of samples obtained from patients with Covid-19; the members of the Joint Committee on Vaccination and Immunisation and the U.K. Variant Technical Group for advice and feedback in developing this study; and Dr. Neil Ferguson for advice on the analysis.
 
(Reference)
(1)
Jamie Lopez Bernal, F.F.P.H., Ph.D., Nick Andrews, Ph.D., Charlotte Gower, D.Phil., Eileen Gallagher, Ph.D., Ruth Simmons, Ph.D., Simon Thelwall, Ph.D., Julia Stowe, Ph.D., Elise Tessier, M.Sc., Natalie Groves, M.Sc., Gavin Dabrera, M.B., B.S., F.F.P.H., Richard Myers, Ph.D., Colin N.J. Campbell, M.P.H., F.F.P.H., Gayatri Amirthalingam, M.F.P.H., Matt Edmunds, M.Sc., Maria Zambon, Ph.D., F.R.C.Path., Kevin E. Brown, M.R.C.P., F.R.C.Path., Susan Hopkins, F.R.C.P., F.F.P.H., Meera Chand, M.R.C.P., F.R.C.Path., and Mary Ramsay, M.B., B.S., F.F.P.H.
Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant
The New England Journal of Medicine July 21, 2021
---
Author Affiliations
From Public Health England (J.L.B., N.A., C.G., E.G., R.S., S.T., J.S., E.T., N.G., G.D., R.M., C.N.J.C., G.A., M.E., M.Z., K.E.B., S.H., M.C., M.R.), the National Institute of Health Research (NIHR) Health Protection Research Unit in Vaccines and Immunisation, London School of Hygiene and Tropical Medicine (J.L.B., N.A., C.N.J.C., G.A., K.E.B., M.R.), the NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London (J.L.B., M.Z.), and Guy’s and St. Thomas’ Hospital NHS Trust (M.C.), London, and Healthcare Associated Infections and Antimicrobial Resistance, University of Oxford, Oxford (S.H.) — all in the United Kingdom.
(2)
Public Health England. SARS-CoV-2 variants  of  concern  and  variants  under investigation in England. Technical briefing 11. May 13, 2021
(https://assets . publishing . service . gov . uk/  government/  uploads/  system/  uploads/  attachment_data/  file/  986380/  Variants_of_Concern_VOC_Technical _Briefing_11_England . pdf).
(3)
Johnson BA, Xie X, Kalveram B, et al.
Furin cleavage site is key to SARS-CoV-2 pathogenesis.  August  26,  2020 
(https://www . biorxiv . org/  content/  10 . 1101/  2020 . 08 . 26 . 268854v1). preprint.
(4)
Polack FP, Thomas SJ, Kitchin N, et al.
Safety  and  efficacy  of  the  BNT162b2 mRNA Covid-19 vaccine.
N Engl J Med 2020; 383: 2603-15.
(5)
Voysey M, Clemens SAC, Madhi SA, et al.
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)
Baden LR, El Sahly HM, Essink B, et al.
Efficacy  and  safety  of  the  mRNA-1273 SARS-CoV-2 vaccine.
N Engl J Med 2021; 384: 403-16.
(7)
Lopez Bernal J, Andrews N, Gower C, et al.
Effectiveness of the Pfizer-BioNTech and  Oxford-AstraZeneca  vaccines  on  covid-19 related symptoms, hospital ad-missions, and mortality in older adults in England: test negative case-control study.
BMJ 2021; 373: n1088.
(8)
Hall  VJ,  Foulkes  S,  Saei  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: 1725-35.
(9)
Shrotri M, Krutikov M, Palmer T, et al.
Vaccine effectiveness of the first dose of ChAdOx1 nCoV-19 and BNT162b2 against SARS-CoV-2 infection in residents of long-term care facilities (VIVALDI study).
March 26, 2021 (https://www . medrxiv . org/  content/  10 . 1101/  2021 . 03 . 26 . 21254391v1). preprint.
(10)
Thompson MG, Burgess JL, Naleway AL, et al.
Interim estimates of vaccine effectiveness of BNT162b2 and mRNA-1273 COVID-19  vaccines  in  preventing  SARS-CoV-2  infection  among  health  care  personnel, first responders, and other essential and frontline workers — eight U.S. locations,  December  2020–March  2021.
MMWR Morb Mortal Wkly Rep 2021; 70: 495-500.
(11)
Dagan  N,  Barda  N,  Kepten  E,  et  al.
BNT162b2  mRNA  Covid-19  vaccine  in  a  nationwide  mass  vaccination  setting.
N Engl J Med 2021; 384: 1412-23.