Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial

被引：18

作者：

Liu, Xinxue ^{[1
,33
]}

Wright, Annie ^{[4
]}

Feng, Shuo ^{[1
]}

Janani, Leila ^{[4
]}

Aley, Parvinder K. ^{[1
,5
]}

Babbage, Gavin ^{[2
]}

Baker, Jonathan ^{[2
,3
]}

Baxter, David ^{[6
]}

Bawa, Tanveer ^{[7
]}

Bula, Marcin ^{[8
]}

Cathie, Katrina ^{[2
,3
]}

Chatterjee, Krishna ^{[9
]}

Dodd, Kate ^{[8
]}

Enever, Yvanne ^{[10
]}

Fox, Lauren ^{[11
]}

Qureshi, Ehsaan ^{[12
]}

Goodman, Anna L. ^{[7
,13
]}

Green, Christopher A. ^{[12
]}

Haughney, John ^{[14
]}

Hicks, Alexander ^{[11
]}

Jones, Christine E. ^{[2
,3
]}

Kanji, Nasir ^{[1
]}

Klaauw, Agatha A. van der ^{[15
]}

Libri, Vincenzo ^{[16
]}

Llewelyn, Martin J. ^{[17
]}

Mansfield, Rebecca ^{[18
]}

Maallah, Mina ^{[19
]}

McGregor, Alastair C. ^{[19
]}

Minassian, Angela M. ^{[1
,20
]}

Moore, Patrick ^{[21
]}

Mughal, Mehmood ^{[6
]}

Mujadidi, Yama F. ^{[5
]}

Belhadef, Hanane Trari ^{[5
]}

Holliday, Kyra ^{[22
]}

Osanlou, Orod ^{[23
]}

Osanlou, Rostam ^{[24
]}

Owens, Daniel R. ^{[2
,3
]}

Pacurar, Mihaela ^{[2
,3
]}

Palfreeman, Adrian ^{[25
]}

Pan, Daniel ^{[25
,26
]}

Rampling, Tommy

Regan, Karen

Saich, Stephen

Saralaya, Dinesh ^{[27
]}

Sharma, Sunil

Sheridan, Ray ^{[28
]}

Stokes, Matthew ^{[2
]}

Thomson, Emma C. ^{[29
]}

Todd, Shirley

Twelves, Chris ^{[22
]}

机构：

[1] Univ Oxford, Dept Paediat, Oxford Vaccine Grp, Oxford, England

[2] Univ Hosp Southampton NHS Fdn Trust, NIHR Southampton Clin Res Facil & Biomed Res Ctr, Southampton, England

[3] Univ Southampton, Fac Med, Southampton, England

[4] Imperial Coll London, Imperial Clin Trials Unit, London, England

[5] NIHR Oxford Biomed Res Ctr, Oxford, England

[6] Stockport NHS Fdn Trust, Stockport, England

[7] Guys & St ThomasNHS Fdn Trust, Dept Infect, London, England

[8] NIHR Liverpool Clin Res Facil, Liverpool, England

[9] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Clin Res Facil, Cambridge, England

[10] PHARMExcel, Welwyn Garden City, England

[11] Portsmouth Hosp Univ NHS Trust, Portsmouth, England

[12] Univ Hosp Birmingham NHS Fdn Trust, NIHR Wellcome Clin Res Facil, Birmingham, England

[13] UCL, MRC Clin Trials Unit, London, England

[14] Queen Elizabeth Univ Hosp, NHS Greater Glasgow & Clyde, Glasgow, Scotland

[15] Univ Cambridge, Dept Clin Biochem, Wellcome MRC Inst Metab Sci, Cambridge, England

[16] Univ Coll London Hosp NHS Fdn Trust, NIHR UCLH Clin Res Facil, London, England

[17] Univ Hosp Sussex NHS Fdn Trust, Brighton, England

[18] Dorset Res Hub, Bournemouth, England

[19] London Northwest Univ Healthcare, Dept Infect Dis & Trop Med, London, England

[20] Univ Oxford, Jenner Inst, Nuffield Dept Med, Oxford, England

[21] Adam Practice, Poole, England

[22] Univ Leeds, Leeds Teaching Hosp Trust, NIHR Leeds Clin Res Facil, Leeds, England

[23] Bangor Univ, Betsi Cadwaladr Univ Hlth Board, Publ Hlth Wales, Bangor, England

[24] Univ Liverpool, Liverpool, England

[25] Univ Leicester, Univ Hosp Leicester NHS Trust, Leicester, England

[26] Univ Leicester, Dept Resp Sci, Leicester, England

[27] Bradford Teaching Hosp NHS Fdn Trust, Bradford Inst Hlth Res, Bradford, England

[28] Royal Devon & Exeter Hosp NHS Fdn Trust, Exeter, England

[29] MRC Univ Glasgow Ctr Virus Res, Glasgow, Scotland

[30] UK Hlth Secur Agcy, Porton Down, England

[31] UK Hlth Secur Agcy, Colindale, London, England

[32] Univ Nottingham, Sch Med, Lifespan & Populat Hlth Unit, Nottingham, England

[33] Churchill Hosp, Ctr Vaccinol & Trop Med, Oxford Vaccine Grp, Oxford OX3 7LA, England

[34] Univ Hosp Southampton NHS Fdn Trust, NIHR Southampton Clin Res Facil, Southampton SO16 6YD, England

来源：

JOURNAL OF INFECTION | 2023年 / 87卷 / 01期

基金：

美国国家卫生研究院;

关键词：

COVID-19; SARS-CoV-2; Vaccination; Immunisation; Immunogenicity; Antibodies; T-Cells; Boosters;

D O I：

10.1016/j.jinf.2023.04.012

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

Background: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vac-cines from day (D) 28 to D242 following third doses in seven study arms. Methods: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) de-livered at three groups of six sites. Participants in each site group were randomised to three or four ex-perimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford-AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer-BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naive during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation.Results: Among the 817 participants included in this report, the median age was 72 years (IQR: 55-78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both popula-tions who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became sig-nificantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms.Conclusions: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns.& COPY; 2023 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

引用

页码：18 / 26

页数：9