Details

Autor(en) / Beteiligte

• Goodyear, Carl S
• Patel, Amit
• Barnes, Eleanor
• Willicombe, Michelle
• Siebert, Stefan
• de Silva, Thushan I
• Snowden, John A
• Lim, Sean H
• Bowden, Sarah J
• Billingham, Lucinda
• Carroll, Miles
• Carr, Edward J
• Beale, Rupert
• Rea, Daniel
• Parry, Helen
• Pirrie, Sarah
• Satsangi, Jack
• Dunachie, Susanna J
• Cook, Gordon
• Basu, Neil
• Gilmour, Ashley
• Hodgkins, Anne-Marie
• Evans, Lili
• Hughes, Ana
• Yong, Kwee L
• A'Hearne, Matthew J
• Koh, Mickey B C
• Burns, Siobhan O
• Paterson, Caron
• McIlroy, Graham
• Murray, Sam M
• Goulston, Lyndsey
• Miller, Samantha
• Keillor, Victoria
• Prendecki, Maria
• Kirkham, Amanda
• Kearns, Pamela
• Beesley, Richard
• Churchill, Vicky
• Insch, Elspeth
• Loughton, Holly
• MacDonald, Eilean
• Lax, Siân
• Magwaro, Sophia
• Gradwell, Mark
• Kinsella, Francesca
• Rolfe, Hayley
• Mortimer, Paige
• Al-Taei, Saly
• Tadros, Susan
• Workman, Sarita
• Arnott, Maxine
• Brock, James
• Melville, Andrew
• Najm, Aurelie
• Rutherford, Matthew
• Sunzini, Flavia
• Herman, Lou S
• Hobbs, Agnieszka
• Ragno, Martina
• Wu, Mary Y
• Selby, Rachael
• Clay, Jennifer
• Lown, Robert
• Lwin, May N
• Kelleher, Peter
• Lightstone, Liz
• Walters, Thomas
• Denyer, Jayne
• Ibrahim, Rahima
• Gleeson, Sarah
• Martin, Paul
• McAdoo, Stephen
• Baker, Helena
• Horswill, Sarah
• Parungao, Nina
• Saich, Stephen
• Cullinane, James
• Irwin, Sophie
• Klenerman, Paul
• Marjot, Thomas
• Chakraverty, Ronjon
• Holroyd, Christopher
• Kavi, Janki
• Trown, Doreen
• Chackathayil, Julia
• Faria, Patricia
• Ingham, Karen
• Miah, Murad
• Miranda, Mauro
• Smith, Callie
• Driver, Kimberley
• Gauntlett, Kaylee
• Farthing, Andrew
• Rundell, Suzann
• Woolcock, Kieran
• Laidlaw, Stephen
• Malik, Zainab
• Nguyen, Dung
• Tipton, Tom

Titel

Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial

Ist Teil von

• The Lancet. Rheumatology, 2024-06, Vol.6 (6), p.e339-e351

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies. OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies. We recruited patients who were immunocompromised from 11 UK hospitals, aged at least 18 years, with previous sub-optimal responses to two doses of SARS-CoV-2 vaccine. Participants were randomly assigned 1:1 (1:1:1 for those with lymphoid malignancies), stratified by disease, previous vaccination type, and anti-spike antibody response following two doses. Individuals with lived experience of immune susceptibility were involved in the study design and implementation. The primary outcome was vaccine-specific immunity defined by anti-SARS-CoV-2 spike antibodies (Roche Diagnostics UK and Ireland, Burgess Hill, UK) and T-cell responses (Oxford Immunotec, Abingdon, UK) before and 21 days after the third vaccine dose analysed by a modified intention-to-treat analysis. The trial is registered with the ISRCTN registry, ISRCTN 15354495, and the EU Clinical Trials Register, EudraCT 2021-003632-87, and is complete. Between Aug 4, 2021 and Mar 31, 2022, 804 participants across nine disease cohorts were randomly assigned to receive BNT162b2 (n=377), mRNA-1273 (n=374), or NVX-CoV2373 (n=53). 356 (45%) of 789 participants were women, 433 (55%) were men, and 659 (85%) of 775 were White. Anti-SARS-CoV-2 spike antibodies measured 21 days after the third vaccine dose were significantly higher than baseline pre-third dose titres in the modified intention-to-treat analysis (median 1384 arbitrary units [AU]/mL [IQR 4·3–7990·0] compared with median 11·5 AU/mL [0·4–63·1]; p<0·001). Of participants who were baseline low responders, 380 (90%) of 423 increased their antibody concentrations to more than 400 AU/mL. Conversely, 166 (54%) of 308 baseline non-responders had no response after the third dose. Detectable T-cell responses following the third vaccine dose were seen in 494 (80%) of 616 participants. There were 24 serious adverse events (BNT612b2 eight [33%] of 24, mRNA-1273 12 [50%], NVX-CoV2373 four [17%]), two (8%) of which were categorised as vaccine-related. There were seven deaths (1%) during the trial, none of which were vaccine-related. A third vaccine dose improved the serological and T-cell response in the majority of patients who are immunocompromised. Individuals with chronic renal disease, lymphoid malignancy, on B-cell targeted therapies, or with no serological response after two vaccine doses are at higher risk of poor response to a third vaccine dose. Medical Research Council, Blood Cancer UK.