B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa
EBioMedicine
; 93(104666): 1-12, jul 3, 2023. tab, ilus, graf
Article
in English
| RSDM
| ID: biblio-1560971
Responsible library:
MZ1.1
RESUMEN
Despite antiretroviral treatment (ART), immune dysfunction persists in children with perinatal HIV infection (HEI). Here we investigated the impact of HIV status on maternal antibody (Ab) passage, long-term vaccine induced immunity and B-cell maturation. Methods:
46 HIV Exposed Uninfected (HEU), 43 HEI, and 15 HIV unexposed uninfected (HUU) infants were vaccinated with 3 doses of DTaP-HepB-Hib-PCV10-OP at 2, 3, and 4 months at Matola Provincial Hospital, Maputo, Mozambique. Tetanus toxoid specific (TT) IgG, HIV Ab and B-cell phenotype characteristics were evaluated at entry, pre-ART, 5, 10, and 18 months in this longitudinal cohort study.Findings:
Baseline (maternal) plasma TT Ab levels were significantly lower in HEI compared to both HEU and HUU and a faster decay of TT Ab was observed in HEI compared to HEU with significantly lower TT Ab levels at 10 and 18 months of age. TT unprotected (UP) (≤0.1 IU/mL) HEI showed higher HIV-RNA at entry and higher longitudinal HIV viremia (Area Under the Curve) compared to TT protected (P) HEI. A distinct HIV-Ab profile was found at entry in HEI compared to HEU. B-cell phenotype showed a B-cell perturbation in HEI vs HEU infants at entry (mean age 40.8 days) with lower transitional CD10+CD19+ B-cells and IgD+CD27- naive B-cells and an overall higher frequency of IgD-CD27- double negative B-cell subsets in HEI.Interpretation:
B-cell perturbation, presenting with higher double negative IgD-CD27- B-cells was observed in neonatal age and may play a major role in the B-cell exhaustion in HEI. The ability to maintain TT protective Ab titers over time is impaired in HEI with uncontrolled viral replication and the current vaccination schedule is insufficient to provide long-term protection against tetanus.Funding:
This work was supported by NIH grant to SP (5R01AI127347-05); Children's Hospital Bambino Gesú (Ricerca corrente 2019) to NC, and Associazione Volontari Bambino Gesù to PP.
Full text:
Available
Collection:
National databases
/
MZ
Database:
RSDM
Main subject:
Anti-Retroviral Agents
Limits:
Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Country/Region as subject:
Africa
Language:
English
Journal:
EBioMedicine
Year:
2023
Document type:
Article
Institution/Affiliation country:
Chair of pediatrics, department of systems medicine, university of rome "Tor Vergata"/IT
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Clinical immunology and vaccinology unit, bambino gesù children's hospital/IT
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Clinical immunology and vaccinology unit, bambino gesù children's hospital, IRCCS/IT
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Clinical lmmunology and vaccinology unit, bambino gesù children's hospital/IT
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Department of microbiology and immunology, miami center for AIDS research/US
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Department of microbiology and immunology, miami center for AIDS research, miller School of medicine, University of miam/US
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Department of microbiology and immunology, miami center for AIDS research, miller school of medicine, university of miami/US
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Department of microbiology and immunology, miami center for AIDS research, miller school of medicine, university of miami,/US
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Fundação ariel glaser contra o SIDA pediatrico/MZ
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Instituto nacional de saúde, marracuene/MZ