Attenuated humoral responses in HIV infection after SARS-CoV-2 vaccination are linked to global B cell defects and cellular immune profiles

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

People 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.

Author list



  1. Institute for Immunity and Transplantation, Division of Infection and Immunity, University College London, UK
  2. Nuffield Department of Medicine, University of Oxford, UK
  3. Cambridge Institute of Therapeutic Immunology and Infectious Disease, Department of Medicine, University of Cambridge, UK
  4. Mortimer Market Centre, Department of HIV, Central and North West London NHS Trust, UK
  5. Institute for Global Health, University College London, UK
  6. The Ian Charleson Day Centre, Royal Free Hospital NHS Foundation Trust UK
  7. NHS Blood and Transplant, Cambridge, UK


Emma Touizer1, Aljawharah Alrubbayi1,2, Rosemarie Ford1, Noshin Hussain1, Pehuén Pereyra Gerber3, Hiu-Long Shum1, Chloe Rees-Spear1, Luke Muir1, Ester Gea-Mallorquí2, Jakub Kopycinski2, Dylan Jankovic1, Christopher Pinder1, Thomas A Fox1, Ian Williams4, Claire Mullender5, Irfaan Maan4,5, Laura Waters4, Margaret Johnson1,6, Sara Madge6, Michael Youle1,6, Tristan Barber5,6, Fiona Burns5,6, Sabine Kinloch1,6, Sarah Rowland-Jones2, Richard Gilson4,5, Nicholas J Matheson3,7, Emma Morris1, Dimitra Peppa1,4,5 and Laura E McCoy1*

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