@article{Goodyear_C-2024_181405,
title = {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},
author = {Goodyear, C. and Patel, A. and Barnes, E. and Willicombe, M. and Siebert, S. and de Silva, T. and Snowden, J. and Lim, S. and Bowden, S. and Billingham, L. and Richter, A. and Carroll, M. and Carr, E. and Beale, R. and Rea, D. and Parry, H. and Pirrie, S. and Lim, Z. and Satsangi, J. and Dunachie, S. and Cook, G. and Miller, P. and Basu, N. and Gilmour, A. and Hodgkins, A. and Evans, L. and Hughes, A. and Longet, S. and Meacham, G. and Yong, K. and A'Hearne, M. and Koh, M. and Burns, S. and Orchard, K. and Paterson, C. and McIlroy, G. and Murray, S. and Thomson, T. and Dimitriadis, S. and Goulston, L. and Miller, S. and Keillor, V. and Prendecki, M. and Thomas, D. and Kirkham, A. and McInnes, I. and Kearns, P.},
month = {may},
year = {2024},
abstract = {Background 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. Methods 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. Findings 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&lt;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. Interpretation 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.},
pages = {E339-E351},
volume = {6},
issue = {6},
journal = {The Lancet Rheumatology},
publisher = {Elsevier},
url = {http://dx.doi.org/10.1016/S2665-9913(24)00065-1},
}
