B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, AfricaResearch in context
Nicola Cotugno,
Suresh Pallikkuth,
Marco Sanna,
Vinh Dinh,
Lesley de Armas,
Stefano Rinaldi,
Sheldon Davis,
Giulia Linardos,
Giuseppe Rubens Pascucci,
Rajendra Pahwa,
Nadia Sitoe,
Paula Vaz,
Paolo Rossi,
Maria Grazia Lain,
Paolo Palma,
Savita Pahwa
Affiliations
Nicola Cotugno
Clinical Immunology and Vaccinology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome 00165, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy
Suresh Pallikkuth
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States
Marco Sanna
Clinical Immunology and Vaccinology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome 00165, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy
Vinh Dinh
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States
Lesley de Armas
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States
Stefano Rinaldi
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States
Sheldon Davis
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States
Giulia Linardos
Microbiology and Diagnostic Immunology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome 00165, Italy
Giuseppe Rubens Pascucci
Clinical Immunology and Vaccinology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome 00165, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy
Rajendra Pahwa
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States
Nadia Sitoe
Fundação Ariel Glaser Contra o SIDA Pediatrico, Maputo, Mozambique
Paula Vaz
Instituto Nacional de Saúde, Marracuene, Maputo Province, Mozambique
Paolo Rossi
Chair of Pediatrics, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy
Maria Grazia Lain
Fundação Ariel Glaser Contra o SIDA Pediatrico, Maputo, Mozambique
Paolo Palma
Clinical Immunology and Vaccinology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome 00165, Italy; Chair of Pediatrics, Department of Systems Medicine, University of Rome “Tor Vergata”, Rome 00133, Italy; Corresponding author. Clinical Immunology and Vaccinology Unit, Children Hospital Bambino Gesù, IRCCS, University of Rome “Tor Vergata”, Rome, Italy.
Savita Pahwa
Department of Microbiology and Immunology, Miami Center for AIDS Research, Miller School of Medicine, University of Miami, Miami, United States; Corresponding author. Department of Microbiology and Immunology, University of Miami, Miami, United States.
Summary: Background: 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.
