Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.

Tytuł:: Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.
Autorzy:: Barrett JR; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Belij-Rammerstorfer S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Dold C; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Ewer KJ; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Folegatti PM; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Gilbride C; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Halkerston R; Public Health England, Salisbury, UK.
Hill J; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Jenkin D; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. .
Stockdale L; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Verheul MK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Aley PK; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Angus B; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Bellamy D; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Berrie E; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Bibi S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Bittaye M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Carroll MW; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Cavell B; Public Health England, Salisbury, UK.
Clutterbuck EA; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Edwards N; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Flaxman A; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Fuskova M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Gorringe A; Public Health England, Salisbury, UK.
Hallis B; Public Health England, Salisbury, UK.
Kerridge S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Lawrie AM; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Linder A; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Liu X; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Madhavan M; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Makinson R; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Mellors J; Public Health England, Salisbury, UK.
Minassian A; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Moore M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Mujadidi Y; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Plested E; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Poulton I; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Ramasamy MN; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Robinson H; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Rollier CS; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Song R; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Snape MD; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Tarrant R; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Taylor S; Public Health England, Salisbury, UK.
Thomas KM; Public Health England, Salisbury, UK.
Voysey M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Watson MEE; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Wright D; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Douglas AD; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Green CM; Clinical BioManufacturing Facility, The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Hill AVS; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Lambe T; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Gilbert S; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Pollard AJ; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. .
Corporate Authors:: Oxford COVID Vaccine Trial Group
Źródło:: Nature medicine [Nat Med] 2021 Feb; Vol. 27 (2), pp. 279-288. Date of Electronic Publication: 2020 Dec 17.
Typ publikacji:: Clinical Trial, Phase I; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: New York Ny : Nature Publishing Company
Original Publication: New York, NY : Nature Pub. Co., [1995-
MeSH Terms:: Immunization, Secondary*
Antibody Formation/*immunology
COVID-19/*immunology
COVID-19 Vaccines/*immunology
SARS-CoV-2/*immunology
Adolescent ; Adult ; Antibodies, Neutralizing/immunology ; ChAdOx1 nCoV-19 ; Dose-Response Relationship, Drug ; Genetic Vectors/immunology ; Humans ; Middle Aged ; Spike Glycoprotein, Coronavirus/immunology ; Time Factors ; Young Adult
References:: WHO COVID-19. Draft Landscape of COVID-19 Candidate Vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (2020).
Zhu, F. C. et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 396, 479–488 (2020). (PMID: 10.1016/S0140-6736(20)31605-6)
Logunov, D. Y. et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1/2 studies from Russia. Lancet 396, 887–897 (2020). (PMID: 10.1016/S0140-6736(20)31866-3)
Jackson, L. A. et al. An mRNA vaccine against SARS-CoV-2—preliminary report. N. Engl. J. Med. https://doi.org/10.1056/nejmoa2022483 (2020).
Xia, S. et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials. JAMA 324, 951–960 (2020). (PMID: 10.1001/jama.2020.15543)
Xia, S. et al. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(20)30831-8 (2020).
Yu, J. et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science 369, 806–811 (2020). (PMID: 10.1126/science.abc6284)
Mercado, N. B. et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature https://doi.org/10.1038/s41586-020-2607-z (2020).
Robbiani, D. F. et al. Convergent antibody responses to SARS-CoV-2 in convalescent individuals. Nature 584, 437–442 (2020). (PMID: 10.1038/s41586-020-2456-9)
Wu, F. et al. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications. Preprint at medRxiv https://doi.org/10.1101/2020.03.30.20047365 (2020).
Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395, 1054–1062 (2020). (PMID: 10.1016/S0140-6736(20)30566-3)
Levin, A. T., Cochran, K. B. & Walsh, S. P. Assessing the age specificity of infection fatality rates for COVID-19: meta-analysis & public policy implications. Preprint at medRxiv https://doi.org/10.1101/2020.07.23.20160895 (2020).
Chandrashekar, A. et al. SARS-CoV-2 infection protects against rechallenge in rhesus macaques. Science 369, 812–817 (2020). (PMID: 10.1126/science.abc4776)
Atyeo, C. et al. Distinct early serological signatures track with SARS-CoV-2 survival. Immunity 53, 1–9 (2020). (PMID: 10.1016/j.immuni.2020.07.020)
Grifoni, A. et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489–1501 (2020). (PMID: 10.1016/j.cell.2020.05.015)
Sekine, T. et al. Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. Cell 183, 158–168 (2020). (PMID: 10.1016/j.cell.2020.08.017)
Folegatti, P. M. et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet 396, 467–478 (2020). (PMID: 10.1016/S0140-6736(20)31604-4)
Keech, C. et al. Phase 1–2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N. Engl. J. Med. 1–13 https://doi.org/10.1056/nejmoa2026920 (2020).
Walsh, E. E. et al. Safety and immunogenicity of two RNA-Based COVID-19 vaccine candidates. N. Engl. J. Med. 1–13 https://doi.org/10.1056/nejmoa2027906 (2020).
Hodgson, S. H. et al. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen ama1: report on a phase 1a clinical trial. Mol. Ther. 22, 2142–2154 (2014). (PMID: 10.1038/mt.2014.157)
Payne, R. O. et al. Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions. JCI Insight 2, 1–19 (2017).
Barouch, D. et al. Evaluation of a mosaic HIV-1 vaccine in a randomized, double-blinded, placebo-controlled phase I/IIa clinical trial and in rhesus monkeys. Lancet 392, 232–243 (2018). (PMID: 10.1016/S0140-6736(18)31364-3)
Ewer, K. et al. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat. Med. https://doi.org/10.1038/s41591-020-01194-5 (2021).
Sahin, U. et al. COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses. Nature https://doi.org/10.1038/s41586-020-2814-7 (2020).
Anywaine, Z. et al. Safety and immunogenicity of a 2-dose heterologous vaccination regimen with Ad26.ZEBOV and MVA-BN-Filo ebola vaccines: 12-month data from a phase 1 randomized clinical trial in Uganda and Tanzania. J. Infect. Dis. 220, 46–56 (2019). (PMID: 10.1093/infdis/jiz070)
Williams, K. et al. Phase 1 safety and immunogenicity study of a respiratory syncytial virus vaccine with an adenovirus 26 vector encoding prefusion F (Ad26.RSV.preF) in adults aged ≥60 years. J. Infect. Dis. 222, 979–988 (2020). (PMID: 10.1093/infdis/jiaa193)
Sadoff, J. et al. Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate: interim results of a phase 1/2a, double-blind, randomized, placebo-controlled trial. Preprint at medRxiv https://doi.org/10.1101/2020.09.23.20199604 (2020).
Rydyznski Moderbacher, C. et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell 183, 996–1012 (2020). (PMID: 10.1016/j.cell.2020.09.038)
Sridhar, S. et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat. Med. https://doi.org/10.1038/nm.3350 (2013).
McMichael, A. J., Gotch, F. M., Noble, G. R. & Beare, P. A. S. Cytotoxic T cell immunity to influenza. N. Engl. J. Med. https://doi.org/10.1056/nejm198307073090103 (1983).
Wilkinson, T. M. et al. Preexisting influenza-specific CD4 T cells correlate with disease protection against influenza challenge in humans. Nat. Med. https://doi.org/10.1038/nm.2612 (2012).
Wyllie, D. et al. SARS-CoV-2 responsive T cell numbers are associated with protection from COVID-19: a prospective cohort study in keyworkers. Preprint at medRxiv https://doi.org/10.1101/2020.11.02.20222778 (2020).
Zhao, J., Zhao, J. & Perlman, S. T Cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice. J. Virol. https://doi.org/10.1128/jvi.01049-10 (2010).
Seo, S. H., Pei, J., Briles, W. E., Dzielawa, J. & Collisson, E. W. Adoptive transfer of infectious bronchitis virus primed αβ T cells bearing CD8 antigen protects chicks from acute infection. Virology https://doi.org/10.1006/viro.2000.0211 (2000).
Fenrich, M. et al. SARS-CoV-2 dissemination through peripheral nerves explains multiple organ injury. Front. Cell. Neurosci. 14, 1–12 (2020). (PMID: 10.3389/fncel.2020.00229)
Payne, R. O. et al. Human vaccination against Plasmodium vivax Duffy-binding protein induces strain-transcending antibodies. JCI Insight 2, e93683 (2017). (PMID: 10.1172/jci.insight.93683)
Biswas, S. et al. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure. PLoS ONE 9, e107903 (2014).
Excler, J. L., Ake, J., Robb, M. L., Kim, J. H. & Plotkin, S. A. Nonneutralizing functional antibodies: a new ‘old’ paradigm for HIV vaccines. Clin. Vaccine Immunol. 21, 1023–1036 (2014). (PMID: 10.1128/CVI.00230-14)
DiLillo, D., Tan, G., Palese, P. & Ravetch, J. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo. Nat. Med. 20, 143–151 (2014). (PMID: 10.1038/nm.3443)
Buchbinder, S. P. et al. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet https://doi.org/10.1016/S0140-6736(08)61591-3 (2008).
Koch, T. et al. Safety and immunogenicity of a modified vaccinia virus Ankara vector vaccine candidate for Middle East respiratory syndrome: an open-label, phase 1 trial. Lancet Infect. Dis. https://doi.org/10.1016/S1473-3099(20)30248-6 (2020).
Reisinger, E. C. et al. Immunogenicity, safety and tolerability of the measles-vectored chikungunya virus vaccine MV-CHIK: a double-blind, randomised, placebo-controlled and active-controlled phase 2 trial. Lancet https://doi.org/10.1016/S0140-6736(18)32488-7 (2018).
Ledgerwood, J. E. et al. Chimpanzee adenovirus vector Ebola vaccine. N. Engl. J. Med. https://doi.org/10.1056/nejmoa1410863 (2017).
Li, J. X. et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob. Health https://doi.org/10.1016/S2214-109X(16)30367-9 (2017).
Dicks, M. D. J. et al. A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity. PLoS ONE 7, e40385 (2012).
Petropoulos, C. J. et al. A novel phenotypic drug susceptibility assay for human immunodeficiency virus type 1. Antimicrob. Agents Chemother. 44, 920–928 (2000). (PMID: 10.1128/AAC.44.4.920-928.2000)
Richman, D. D., Wrin, T., Little, S. J. & Petropoulos, C. J. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc. Natl Acad. Sci. USA 100, 4144–4149 (2003). (PMID: 10.1073/pnas.0630530100)
Whitcomb, J. M. et al. Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob. Agents Chemother. 51, 566–575 (2007). (PMID: 10.1128/AAC.00853-06)
Binyamin, L. et al. Blocking NK cell inhibitory self-recognition promotes antibody-dependent cellular cytotoxicity in a model of anti-lymphoma therapy. J. Immunol. 180, 6392–6401 (2008). (PMID: 10.4049/jimmunol.180.9.6392)
Karsten, C. B. et al. A versatile high throughput assay to characterize antibody-mediated neutrophil phagocytosis. J. Immunol. Methods 471, 46–56 (2019). (PMID: 10.1016/j.jim.2019.05.006)
Ackerman, M. E. et al. A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples. J. Immunol. Methods 366, 8–19 (2011). (PMID: 10.1016/j.jim.2010.12.016)
Brown, E. P. et al. High-throughput, multiplexed IgG subclassing of antigen-specific antibodies from clinical samples. J. Immunol. Methods 386, 117–123 (2012). (PMID: 10.1016/j.jim.2012.09.007)
Lesne, E. et al. Acellular pertussis vaccines induce anti-pertactin bactericidal antibodies which drives the emergence of pertactin-negative strains. Front. Microbiol. 11, 2108 (2020). (PMID: 10.3389/fmicb.2020.02108)
Amanat, F. et al. A serological assay to detect SARS-CoV-2 seroconversion in humans. Nat. Med. 26, 1033–1036 (2020). (PMID: 10.1038/s41591-020-0913-5)
Frey, A., Di, J. & Zurakowski, D. A statistically defined endpoint titer determination method for immunoassays. J. Immunol. Methods 221, 35–41 (1998). (PMID: 10.1016/S0022-1759(98)00170-7)
Grant Information:: MR/L006588/1 United Kingdom MRC_ Medical Research Council; MC_UU_00008/11 United Kingdom MRC_ Medical Research Council; MC_PC_19058 United Kingdom MRC_ Medical Research Council; MC_PC_19055 United Kingdom MRC_ Medical Research Council; 109965/Z/15/Z United Kingdom WT_ Wellcome Trust; MR/L018942/1 United Kingdom MRC_ Medical Research Council; G0600520 United Kingdom MRC_ Medical Research Council; G1001046 United Kingdom MRC_ Medical Research Council; MR/T001151/1 United Kingdom MRC_ Medical Research Council
Contributed Indexing:: Investigator: J Aboagye; J Alderson; A Ali; E Allen; L Allen; R Anslow; CV Arancibia-Cárcamo; EH Arbe-Barnes; M Baker; P Baker; N Baker; I Baleanu; E Barnes; L Bates; A Batten; K Beadon; R Beckley; A Beveridge; KR Bewley; EM Bijker; L Blackwell; CL Blundell; E Bolam; E Boland; N Borthwick; A Boyd; T Brenner; P Brown; C Brown-O'Sullivan; E Brunt; J Burbage; KR Buttigieg; N Byard; I Cabrera Puig; S Camara; M Cao; F Cappuccini; M Carr; MW Carroll; J Chadwick; I Chelysheva; JS Cho; L Cifuentes; E Clark; R Colin-Jones; CP Conlon; NS Coombes; R Cooper; WEM Crocker; CJ Cunningham; BE Damratoski; MS Datoo; C Datta; H Davies; T Demissie; C Di Maso; D DiTirro; T Dong; FR Donnellan; N Douglas; C Downing; J Drake; R Drake-Brockman; RE Drury; SJ Dunachie; OE Muhanna; SC Elias; MJ Elmore; KRW Emary; MR English; S Felle; S Feng; CF Da Silva; S Field; R Fisher; KJ Ford; J Fowler; E Francis; J Frater; J Furze; P Galian-Rubio; H Garlant; K Godwin; G Gorini; L Gracie; G Gupta; E Hamilton; J Hamlyn; B Hanumunthadu; SA Harris; D Harrison; TC Hart; S Hawkins; JA Henry; G Hodges; SHC Hodgson; MM Hou; E Howe; N Howell; B Huang; H Humphries; P Iveson; S Jackson; F Jackson; S Jauregui; K Jeffery; E Jones; K Jones; R Kailath; J Keen; S Kelly; D Kelly; E Kelly; D Kerr; L Khan; B Khozoee; A Killen; J Kinch; TB King; L King; L Kingham-Page; P Klenerman; JC Knight; D Knott; S Koleva; CW Larkworthy; JPJ Larwood; EA Lees; A Lelliott; S Leung; Y Li; AM Lias; S Lipworth; S Liu; L Loew; R Lopez Ramon; G Mallett; K Mansatta; NG Marchevsky; S Marinou; E Marlow; JL Marshall; P Matthews; J McEwan; J McGlashan; L McInroy; G Meddaugh; AJ Mentzer; N Mirtorabi; E Morey; R Morgans; SJ Morris; H Morrison; G Morshead; R Morter; N Moya; E Mukhopadhyay; J Muller; C Munro; S Murphy; P Mweu; A Noé; FL Nugent; E Nuthall; K O'Brien; D O'Connor; D O'Donnell; B Oguti; V Olchawski; C Oliveria; PJ O'Reilly; P Osborne; N Owino; K Parker; H Parracho; M Patrick-Smith; Y Peng; E Penn; MP Peralta Alvarez; J Perring; C Petropoulos; K Pfafferott; D Pipini; D Phillips; P Proud; S Provstgaard-Morys; D Pulido; K Radia; D Rajapaksa; F Ramos Lopez; H Ratcliffe; T Rawlinson; ER Pabon; S Rhead; AJ Ritchie; H Roberts; S Roche; I Rudiansyah; S Salvador; H Sanders; K Sanders; I Satti; A Schmid; E Schofield; G Screaton; C Sedik; I Shaik; HR Sharpe; A Shea; S Silk; L Silva-Reyes; DT Skelly; CC Smith; DJ Smith; AJ Spencer; E Stafford; A Szigeti; A Tahiri-Alaoui; R Tanner; IJ Taylor; K Taylor; R Te Water Naude; Y Themistocleous; A Themistocleous; M Thomas; TM Thomas; A Thompson; L Tinh; A Tomic; S Tonks; J Towner; N Tran; JA Tree; A Truby; C Turner; N Turner; M Ulaszewska; R Varughese; I Vichos; L Walker; M Wand; C White; R White; P Williams; AT Worth; T Wrin; XL Yao; D Zizi
Molecular Sequence:: ClinicalTrials.gov NCT04324606
Substance Nomenclature:: 0 (Antibodies, Neutralizing)
0 (COVID-19 Vaccines)
0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)
B5S3K2V0G8 (ChAdOx1 nCoV-19)
Entry Date(s):: Date Created: 20201218 Date Completed: 20210223 Latest Revision: 20230315
Update Code:: 20240105
DOI:: 10.1038/s41591-020-01179-4
PMID:: 33335322
: Czasopismo naukowe

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.

Comment in: Nat Rev Immunol. 2021 Feb;21(2):70-71. (PMID: 33432129)
Erratum in: Nat Med. 2021 Jun;27(6):1113. (PMID: 33958800)

Informacja