TY - JOUR
T1 - Persistence of immunogenicity after seven COVID-19 vaccines given as third dose boosters following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK
T2 - Three month analyses of the COV-BOOST trial
AU - the COV-BOOST study group
AU - Liu, Xinxue
AU - Munro, Alasdair P S
AU - Feng, Shuo
AU - Janani, Leila
AU - Aley, Parvinder K
AU - Babbage, Gavin
AU - Baxter, David
AU - Bula, Marcin
AU - Cathie, Katrina
AU - Chatterjee, Krishna
AU - Dejnirattisai, Wanwisa
AU - Dodd, Kate
AU - Enever, Yvanne
AU - Qureshi, Ehsaan
AU - Goodman, Anna L.
AU - Green, Christopher A
AU - Harndahl, Linda
AU - Haughney, John
AU - Hicks, Alexander
AU - van der Klaauw, Agatha A.
AU - Kwok, Jonathan
AU - Libri, Vincenzo
AU - Llewelyn, Martin J
AU - Mcgregor, Alastair C
AU - Minassian, Angela M.
AU - Moore, Patrick
AU - Mughal, Mehmood
AU - Mujadidi, Yama F
AU - Holliday, Kyra
AU - Osanlou, Orod
AU - Osanlou, Rostam
AU - Owens, Daniel R.
AU - Pacurar, Mihaela
AU - Palfreeman, Adrian
AU - Pan, Daniel
AU - Rampling, Tommy
AU - Regan, Karen
AU - Saich, Stephen
AU - Serafimova, Teona
AU - Saralaya, Dinesh
AU - Screaton, Gavin R
AU - Sharma, Sunil
AU - Sheridan, Ray
AU - Sturdy, Ann
AU - Supasa, Piyada
AU - Thomson, Emma C
AU - Todd, Shirley
AU - Twelves, Christopher J.
AU - Read, Robert C.
AU - Charlton, Sue
N1 - Acknowledgments:
The study is funded by the UK Government through the National Institute for Health Research (NIHR) and the Vaccine Task Force (VTF). The study Sponsor is University Hospital Southampton NHS Foundation Trust, Southampton, UK. ChAd, BNT and m1273 used in this study were supplied by the UK Health Security Agency (previously Public Health England). NVX, VLA, Ad26 and CVn were supplied by the manufacturers, without charge. The research is supported by the NIHR Southampton Clinical Research Facility and Biomedical Research Centre, the NIHR Clinical Research Facilities and NIHR Clinical Research Network and the NIHR funded National Immunisation Schedule Evaluation Consortium (NISEC). SNF and MDS are NIHR Senior Investigators. KC is a Wellcome Trust Investigator (210755/Z/18/Z) and NIHR Senior Investigator Emeritus. GRS and TL received funding from the Chinese Academy of Medical Science (CAMS) Oxford Institute (COI). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The investigators would like to thank the UK Medicines and Healthcare products Regulatory Agency (MHRA) and Heath Research Authority (HRA) for their extraordinary efforts in rapidly reviewing submissions, for their attention to detail and input into trial design. Specific thanks go to Drs Kirsty Wydenbach, Lisa Campbell, David Jones, Graham McNaughton, Marie-Christine Bielsky and David Brown at the MHRA; to Drs David Carpenter (Chair) and Mike Proven (Vice-Chair) and all volunteer officers/members of the South Central, Berkshire Research Ethics Committee; and to Kevin Ahmed and all HRA staff who supported the trial. The investigators express their gratitude for the contribution of all trial participants, the UK Vaccine Task Force (Jacinda Kemps) and the invaluable advice of the trial committees. Professors Andrew Ustianowski (Chair) and Chris Rogers, and Dr Andrew Riordan serve as the independent members of the Data Monitoring and Safety Committee and Professor Robert Read is the Chair of the Trial Steering Committee.
PY - 2022/6
Y1 - 2022/6
N2 - Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters.Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.
AB - Objectives: To evaluate the persistence of immunogenicity three months after third dose boosters.Methods: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose. The analysis was conducted using all randomised participants who were SARS-CoV-2 naïve during the study.Results: Amongst the 2883 participants randomised, there were 2422 SARS-CoV-2 naïve participants until D84 visit included in the analysis with median age of 70 (IQR: 30–94) years. In the participants who had two initial doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd), schedules using mRNA vaccines as third dose have the highest anti-spike IgG at D84 (e.g. geometric mean concentration of 8674 ELU/ml (95% CI: 7461–10,085) following ChAd/ChAd/BNT162b2 (Pfizer-BioNtech, hearafter referred to as BNT)). However, in people who had two initial doses of BNT there was no significant difference at D84 in people given ChAd versus BNT (geometric mean ratio (GMR) of 0.95 (95%CI: 0.78, 1.15). Also, people given Ad26.COV2.S (Janssen; hereafter referred to as Ad26) as a third dose had significantly higher anti-spike IgG at D84 than BNT (GMR of 1.20, 95%CI: 1.01,1.43). Responses at D84 between people who received BNT (15 μg) or BNT (30 μg) after ChAd/ChAd or BNT/BNT were similar, with anti-spike IgG GMRs of half-BNT (15 μg) versus BNT (30 μg) ranging between 0.74–0.86. The decay rate of cellular responses were similar between all the vaccine schedules and doses.Conclusions: 84 days after a third dose of COVID-19 vaccine the decay rates of humoral response were different between vaccines. Adenoviral vector vaccine anti-spike IgG concentrations at D84 following BNT/BNT initial doses were similar to or even higher than for a three dose (BNT/BNT/BNT) schedule. Half dose BNT immune responses were similar to full dose responses. While high antibody tires are desirable in situations of high transmission of new variants of concern, the maintenance of immune responses that confer long-lasting protection against severe disease or death is also of critical importance. Policymakers may also consider adenoviral vector, fractional dose of mRNA, or other non-mRNA vaccines as third doses.
KW - COVID-19 vaccine
KW - Third dose
KW - Heterologous boost
KW - Homologous boost
KW - Fractional dose
KW - Immunogenicity
KW - Persistence
U2 - 10.1016/j.jinf.2022.04.018
DO - 10.1016/j.jinf.2022.04.018
M3 - Article
SN - 0163-4453
VL - 84
SP - 795
EP - 813
JO - Journal of Infection
JF - Journal of Infection
IS - 6
ER -