NVX-CoV2373ワクチンの安全性と効果(イギリスの調査)

//Background//---
 Global population is about 7.8 billion. If herd immunity could be created in the condition where 70 % of the persons have immunity specific to SARS-CoV-2, we need to provide vaccine at least for 5 billion persons which is the 10 billion doses in the booster form. If we need to take vaccination annually like influenza vaccine, we need to manufacture and provide 10 billion doses per a year globally. In addition, preserve condition (cooling) and vaccine price are one of the important matters, but COVAX could ameliorate these problems. However, Given that ongoing mutation and safety concern, increasing vaccine supplier in the world is crucial. Novavax is one of the important vaccine suppliers.
 P.T. Heath et al. evaluate safety and efficacy of NVX-CoV237 SARS-CoV-2 vaccine in the phase-3 clinical trials in the United Kingdom(1). EudraCT number, 2020 - 004123 - 16.
 
//B.1.1.7 variant (Alpha variant)//---
 The main key mutation: N501Y -making affinity binding to ACE2 high
 B.1.1.7 VOC-202012/01- E484K mutations : Immune escape for emergent antibody
 (Emergent history)
 Early October/2020: The southeast of England
 December/2020: London and the rest of the country
 
// NVX-CoV237 vaccine information//---
 Development company: Novavax (The United States of America)
 Nanoparticle with spike protein with Matrix-M adjuvant
 Administration: 50μg / Two-dose regimen / 21 days apart
 The past clinical result:
-A robust immune response and safety profile in healthy adult(2,3)
 
 //Trial period(1)//---
  From September 28 to November 28, 2020 at 33 sites in the United Kingdom.
  Therefore, this is spreading period of B.1.1.7 lineage, so P.T. Heath et al. evaluate efficacy in both B.1.1.7 and no B.1.1.7 cases(1).
 
 //Key exclusion criteria(1)//---
 A history of documented Covid-19 / Having immune deficient manifestation
 
 //Participants characteristics at baseline(1)(See Table 1)//---
 **The condition is almost same between NVX-CoV2373 and Placebo group, so only vaccination group is shown.
 Participate number: 7020 persons (Total 14039 persons)
 Median age: 56(18-84) / ≧65 yr 27.8%
 Race: White 94.4%
 (Risk factor)-
 Obesity BMI>30: 25.4%
 The other risk factors(*): 44.4%
(*)chronic respiratory, cardiac, renal, neurologic, hepatic, immunocompromising conditions, obesity
 
//Safety evaluation (1)(See Figure 2)//---
 General tendency is that severity like Grade2-3 is high frequency after booster dose.
 After booster dose-
 60-80%: Tenderness / Local Adverse event
 40-60%: Pain / Local Adverse event
 20-40%: Headache, Fatigue, Malaise, Muscle pain
 (*)Fever <10% / >38.4℃ 1-2%
 The serious adverse event is low and similar in the two group, so it is not specific.
 
//Efficacy evaluation (1)(See Figure 4)//---
NVX-CoV-2373:(infection)/(parameter) -- Placebo:(infection)/(parameter)
Per-protocol population (2 dose)-Efficacy 89.7% (80.2 to 94.6)
 10/7020 -- 96/7019 ※No severe case in vaccination group
Intention-to-treat population (1 dose)-Efficacy 70.4% (58.3 to 79.1)
 141/7570 -- 42/7569
 ※At least 28 day is needed to get vaccine efficacy. (See Figure 3B)
 Non-B.1.1.7- Efficacy 96.4% (73.8 to 99.5)
 B.1.1.7- Efficacy 86.3% (71.3 to 93.5)
 Coexisting illness Yes - Efficacy 90.9% (70.4 to 97.2) /No 89.1% (76.2 to 95.0)
 
 //Conclusion and Discussion//---
 The vaccine efficacy is comparable to the other mRNA vaccine(4,5). Additionally, hospital burden could be significantly reduced due to no confirmation of severe symptom case in vaccination group. Vaccine safety is significantly acceptable for the infection risk. In order to get vaccine efficacy, we need to wait for at least 28 days after the first dose.
 
//Support//---
Supported by Novavax. Infrastructure support for sites was provided by the NIHR Clinical Research Network.
//Acknowledgment//---
 We(P.T. Heath et al.) thank all the participants who volunteered to participate in this trial and the members of the safety monitoring committee, the NIHR Clinical Research Network, the NIHR Oxford cognitive health Clinical Research Facility, and the UK Vaccine Task Force.
 
(Reference)
(1)
Paul T. Heath, F.R.C.P.C.H., Eva P. Galiza, M.B., B.S., David N. Baxter, M.D., Ph.D., Marta Boffito, M.D., Ph.D., Duncan Browne, M.D., Fiona Burns, Ph.D., David R. Chadwick, Ph.D., Rebecca Clark, M.B., Ch.B., Catherine Cosgrove, Ph.D., James Galloway, Ph.D., Anna L. Goodman, D.Phil., Amardeep Heer, M.B., Ch.B., Andrew Higham, Ph.D., Shalini Iyengar, M.B., B.S., Arham Jamal, M.B., B.Ch., Christopher Jeanes, M.B., B.S., Philip A. Kalra, M.D., Christina Kyriakidou, M.D., Daniel F. McAuley, M.D., Agnieszka Meyrick, M.D., Angela M. Minassian, D.Phil., Jane Minton, Ph.D., Patrick Moore, B.M., B.Sc., Imrozia Munsoor, M.B., B.S., Helen Nicholls, M.B., B.Ch., Orod Osanlou, M.B., Ch.B., Jonathan Packham, D.M., Carol H. Pretswell, M.B., Ch.B., Alberto San Francisco Ramos, L.M.S., Dinesh Saralaya, M.D., Ray P. Sheridan, M.B., Ch.B., Richard Smith, Ph.D., Roy L. Soiza, M.B., Ch.B., Pauline A. Swift, Ph.D., Emma C. Thomson, Ph.D., Jeremy Turner, D.Phil., Marianne E. Viljoen, M.B., Ch.B., Gary Albert, M.S., Iksung Cho, M.S., Filip Dubovsky, M.D., Greg Glenn, M.D., Joy Rivers, Ph.D., Andreana Robertson, M.S., Kathy Smith, M.D., and Seth Toback, M.D. for the 2019nCoV-302 Study Group*
Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine
The New England Journal of Medicine June 30, 2021
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Author Affiliations
From the Vaccine Institute, St. George’s, University of London, and St. George’s University Hospitals NHS Foundation Trust (P.T.H., E.P.G., C.C., A.S.F.R.), Chelsea, Westminster Hospital NHS Foundation Trust and Imperial College London (M.B.), the Institute for Global Health, University College London, and Royal Free London NHS Foundation Trust (F.B.), the Centre for Rheumatic Disease, Kings College London (J.G.), the Department of Infectious Diseases, Guy’s and St. Thomas’ NHS Foundation Trust, MRC Clinical Trials Unit at University College London (A.L.G.), and Renal Services, Epsom and St. Helier University Hospitals NHS Trust (P.A.S.), London, Stockport NHS Foundation Trust, Stepping Hill Hospital, Stockport (D.N.B.), Royal Cornwall Hospitals NHS Trust, Truro (D.B.), Centre for Clinical Infection, South Tees Hospitals NHS Foundation Trust, James Cook University Hospital, Middlesbrough (D.R.C.), Layton Medical Centre, Blackpool (R.C.), Lakeside Healthcare Research, Lakeside Surgeries, Corby (A. Heer), University Hospitals of Morecambe Bay NHS Foundation Trust, Kendal (A. Higham), Accelerated Enrollment Solutions, Synexus Hexham Dedicated Research Site, Hexham General Hospital, Hexham (S.I.), Accelerated Enrollment Solutions, Synexus Thames Valley Dedicated Research Site, Reading (A.J.), Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich (C.J., J.T.), Salford Royal NHS Foundation Trust, Northern Care Alliance, Salford (P.A.K.), Accelerated Enrollment Solutions, Synexus Midlands Dedicated Research Site, Birmingham (C.K.), Wellcome–Wolfson Institute for Experimental Medicine, Queen’s University of Belfast and Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast (D.F.M.), Accelerated Enrollment Solutions, Synexus Merseyside Dedicated Research Site, Liverpool (A.M.), Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, and Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford (A.M.M.), St. James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds (J.M.), the Adam Practice, Poole (P.M.), University Hospital Southampton NHS Foundation Trust, Southampton (P.M.), Accelerated Enrollment Solutions, Synexus Glasgow Dedicated Research Site (I.M.), and MRC–University of Glasgow Centre for Virus Research and Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde (E.C.T.), Glasgow, Accelerated Enrollment Solutions, Synexus Wales Dedicated Research Site, Cardiff (H.N.), the School of Medical Sciences, Bangor University, and Betsi Cadwaladr University Health Board, Bangor (O.O.), the Division of Epidemiology and Public Health, University of Nottingham, Nottingham (J.P.), Haywood Hospital, Midlands Partnership NHS Foundation Trust, Stafford (J.P.), Accelerated Enrollment Solutions, Synexus Lancashire Dedicated Research Site, Chorley (C.H.P.), the National Institute for Health Research Patient Recruitment Centre and Bradford Teaching Hospitals NHS Foundation Trust, Bradford (D.S.), Royal Devon and Exeter Hospital, Exeter (R.P.S.), East Suffolk, North Essex NHS Foundation Trust and University of Essex, Colchester (R.S.), Aberdeen Royal Infirmary, NHS Grampian, and Aging Clinical and Experimental Research Group, University of Aberdeen, Aberdeen (R.L.S.), and Accelerated Enrollment Solutions, Synexus Manchester Dedicated Research Site, Manchester (M.E.V.) — all in the United Kingdom; and Novavax, Gaithersburg, MD (G.A., I.C., F.D., G.G., J.R., A.R., K.S., S.T.).
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