Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV.

Autor: Matveev VA; Dept of Medicine, University of Toronto, Toronto, ON, Canada., Mihelic EZ; Dept of Medicine, University of Toronto, Toronto, ON, Canada., Benko E; Maple Leaf Medical Clinic, Toronto, ON, Canada., Budylowski P; Dept of Medicine, University of Toronto, Toronto, ON, Canada.; Institute of Medical Science, University of Toronto, Toronto, ON, Canada., Grocott S; Dept of Medicine, University of Toronto, Toronto, ON, Canada.; Dept of Microbiology and Immunology, McGill University, Montreal, QC, Canada., Lee T; CIHR Canadian HIV Trials Network (CTN), Vancouver, BC, Canada.; Centre for Health Evaluation and Outcome Sciences (CHÉOS), Vancouver, BC, Canada., Korosec CS; Modelling Infection and Immunity Lab, Mathematics and Statistics Dept, York University, Toronto, ON, Canada.; Centre for Disease Modelling, Mathematics and Statistics Dept, York University, Toronto, ON, Canada., Colwill K; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Stephenson H; Dept of Medicine, University of Toronto, Toronto, ON, Canada.; Dept of Bioengineering, McGill University, Montreal, QC, Canada., Law R; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Ward LA; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Sheikh-Mohamed S; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Mailhot G; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Delgado-Brand M; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Pasculescu A; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Wang JH; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Qi F; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Tursun T; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada., Kardava L; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Chau S; Dept of Medicine, University of Toronto, Toronto, ON, Canada., Samaan P; Dept of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada., Imran A; Dept of Medicine, University of Toronto, Toronto, ON, Canada., Copertino DC Jr; Infectious Diseases, Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA., Chao G; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Choi Y; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Reinhard RJ; Independent Public/Global Health Consultant, San Francisco, CA, USA., Kaul R; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Heffernan JM; Modelling Infection and Immunity Lab, Mathematics and Statistics Dept, York University, Toronto, ON, Canada.; Centre for Disease Modelling, Mathematics and Statistics Dept, York University, Toronto, ON, Canada., Jones RB; Infectious Diseases, Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA.; Dept of Medicine, Weill Cornell Medical College, New York, NY, USA., Chun TW; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Moir S; Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Singer J; CIHR Canadian HIV Trials Network (CTN), Vancouver, BC, Canada.; Centre for Health Evaluation and Outcome Sciences (CHÉOS), Vancouver, BC, Canada.; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada., Gommerman J; Dept of Immunology, University of Toronto, Toronto, ON, Canada., Gingras AC; Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada.; Dept of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Kovacs C; Maple Leaf Medical Clinic, Toronto, ON, Canada.; Dept of Internal Medicine, University of Toronto, Toronto, ON, Canada.; Senior authors., Ostrowski M; Dept of Medicine, University of Toronto, Toronto, ON, Canada.; Dept of Immunology, University of Toronto, Toronto, ON, Canada.; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Unity Health, Toronto, ON, Canada.; Senior authors.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 15. Date of Electronic Publication: 2023 Jun 15.
DOI: 10.1101/2023.06.14.544834
Abstrakt: Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4 + T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV - participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were 'rescued' after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV - participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral 'blips' in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4 + T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.
Databáze: MEDLINE