Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles
Author:
Touizer Emma, Alrubbayi Aljawharah, Ford Rosemarie, Hussain Noshin, Gerber Pehuén Pereyra, Shum Hiu-Long, Rees-Spear Chloe, Muir Luke, Gea-Mallorquí Ester, Kopycinski Jakub, Jankovic Dylan, Pinder Christopher, Fox Thomas AORCID, Williams Ian, Mullender Claire, Maan Irfaan, Waters Laura, Johnson Margaret, Madge Sara, Youle Michael, Barber Tristan, Burns Fiona, Kinloch Sabine, Rowland-Jones Sarah, Gilson Richard, Matheson Nicholas J, Morris EmmaORCID, Peppa Dimitra, McCoy Laura EORCID
Abstract
ABSTRACTPeople living with HIV (PLWH) on suppressive antiretroviral therapy (ART) can have residual immune dysfunction and often display poorer responses to vaccination. We assessed in a cohort of PLWH (n=110) and HIV negative controls (n=64) the humoral and spike-specific B-cell responses following 1, 2 or 3 SARS-CoV-2 vaccine doses. PLWH had significantly lower neutralizing antibody (nAb) titers than HIV-negative controls at all studied timepoints. Moreover, their neutralization breadth was reduced with fewer individuals developing a neutralizing response against the Omicron variant (BA.1) relative to controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs) and pronounced B cell dysfunction. Improved neutralization breadth was seen after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global, but not spike-specific, MBC dysfunction. In contrast to the inferior antibody responses, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, a subset of PLWH with low or absent neutralization had detectable functional T cell responses. These individuals had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination, which may compensate for sub-optimal serological responses in the event of infection. Therefore, normalisation of B cell homeostasis could improve serological responses to vaccines in PLWH and evaluating T cell immunity could provide a more comprehensive immune status profile in these individuals and others with B cell imbalances.
Publisher
Cold Spring Harbor Laboratory
Reference76 articles.
1. Adam, L. , Rosenbaum, P. , Quentric, P. , Parizot, C. , Bonduelle, O. , Guillou, N. , Corneau, A. , Dorgham, K. , Miyara, M. , Luyt, C.E. , et al. (2021). CD8+PD-L1+CXCR3+ polyfunctional T cell abundances are associated with survival in critical SARS-CoV-2-infected patients. JCI Insight 6. 2. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV;Nat Commun,2021 3. Heterologous ChAdOx1/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination: The pragmatic, multi-center, three-arm, partially randomized HEVACC trial;EBioMedicine,2022 4. Baskaran, V. , Lawrence, H. , Lansbury, L.E. , Webb, K. , Safavi, S. , Zainuddin, N.I. , Huq, T. , Eggleston, C. , Ellis, J. , Thakker, C. , et al. (2021). Co-infection in critically ill patients with COVID-19: an observational cohort study from England. J Med Microbiol 70. 5. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease;Immunity,2021
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|