Emergence of neutralizing antibodies associates with clearance of SARS-CoV-2 during HIV-mediated immunosuppression

To design effective vaccines and other immune interventions against a pathogen, it is necessary to know which aspect of immunity associates with protection. We investigated whether neutralizing antibodies associate with infection clearance in long-term SARS-CoV-2 infection during HIV-mediated immunosuppression. We monitored neutralizing antibody activity against SARS-CoV-2 over 1 to 2 years in five participants with advanced HIV disease and delayed control of HIV viremia. These participants had persistent SARS-CoV-2 infection ranging from 110 to 289 days which was associated with low or undetectable neutralizing antibody responses. SARS-CoV-2 clearance was associated with the emergence of neutralizing antibodies and occurred in two participants before suppression of HIV viremia, but after some CD4 T cell reconstitution. Vaccination only further increased neutralizing antibody levels in the advanced HIV disease participants who achieved HIV suppression pre-vaccination. During the prolonged SARS-CoV-2 infection we observed widespread evolution which was particularly pronounced in one Delta variant infection. This resulted in high-level escape from Delta-elicited neutralizing antibodies and a virus antigenically distinct from both ancestral SARS-CoV-2 and Omicron XBB in hamster experimental infections. The results offer new evidence that neutralizing antibodies associate with SARS-CoV-2 clearance and argue that successful management of HIV may be necessary to curtail long-term infection and evolution of co-infecting pathogens..

Medienart:

Preprint

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

bioRxiv.org - (2023) vom: 23. Aug. Zur Gesamtaufnahme - year:2023

Sprache:

Englisch

Beteiligte Personen:

Karim, Farina [VerfasserIn]
Bernstein, Mallory [VerfasserIn]
Jule, Zesuliwe [VerfasserIn]
Lustig, Gila [VerfasserIn]
Upton, Janine-Lee [VerfasserIn]
Ganga, Yashica [VerfasserIn]
Khan, Khadija [VerfasserIn]
Reedoy, Kajal [VerfasserIn]
Mazibuko, Matilda [VerfasserIn]
Govender, Katya [VerfasserIn]
Thambu, Kershnee [VerfasserIn]
Ngcobo, Nokuthula [VerfasserIn]
Venter, Elizabeth [VerfasserIn]
Makhado, Zanele [VerfasserIn]
Hanekom, Willem [VerfasserIn]
von Gottberg, Anne [VerfasserIn]
Karim, Quarraisha Abdool [VerfasserIn]
Abdool Karim, Salim S. [VerfasserIn]
Manickchund, Nithendra [VerfasserIn]
Magula, Nombulelo [VerfasserIn]
Gosnell, Bernadett I. [VerfasserIn]
Moore, Penny L. [VerfasserIn]
Lessells, Richard J. [VerfasserIn]
de Oliveira, Tulio [VerfasserIn]
Moosa, Mahomed-Yunus S. [VerfasserIn]
Sigal, Alex [VerfasserIn]

Links:

Volltext [kostenfrei]

Themen:

570
Biology

doi:

10.1101/2023.08.18.23293746

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI040587886