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Article

Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children

1
Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, 20132 Milan, Italy
2
Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB/IDMIT), University Paris-Saclay, 92265 Fontenay-aux-Roses & Le Kremlin-Bicêtre, France
3
Pediatric Emergency Unit, Filippo Del Ponte Hospital, ASST-Settelaghi, 21100 Varese, Italy
4
Department of Laboratory Medicine, Lund University, 22242 Lund, Sweden
*
Author to whom correspondence should be addressed.
Academic Editors: Nabila Seddiki and Roger Le Grand
Vaccines 2021, 9(3), 260; https://doi.org/10.3390/vaccines9030260
Received: 15 February 2021 / Revised: 5 March 2021 / Accepted: 8 March 2021 / Published: 14 March 2021
(This article belongs to the Special Issue Immune Ontogeny and Vaccination in Early Life)
The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children. View Full-Text
Keywords: HIV-1; neutralization; ADCC; children; humoral immunity; disease progression HIV-1; neutralization; ADCC; children; humoral immunity; disease progression
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MDPI and ACS Style

Dispinseri, S.; Cavarelli, M.; Tolazzi, M.; Plebani, A.M.; Jansson, M.; Scarlatti, G. Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children. Vaccines 2021, 9, 260. https://doi.org/10.3390/vaccines9030260

AMA Style

Dispinseri S, Cavarelli M, Tolazzi M, Plebani AM, Jansson M, Scarlatti G. Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children. Vaccines. 2021; 9(3):260. https://doi.org/10.3390/vaccines9030260

Chicago/Turabian Style

Dispinseri, Stefania, Mariangela Cavarelli, Monica Tolazzi, Anna Maria Plebani, Marianne Jansson, and Gabriella Scarlatti. 2021. "Continuous HIV-1 Escape from Autologous Neutralization and Development of Cross-Reactive Antibody Responses Characterizes Slow Disease Progression of Children" Vaccines 9, no. 3: 260. https://doi.org/10.3390/vaccines9030260

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