B-cell immunity and vaccine induced antibody protection reveal the inefficacy of current vaccination schedule in infants with perinatal HIV-infection in Mozambique, Africa

Article

作者: Pahwa, Rajendra ; Pascucci, Giuseppe Rubens ; Palma, Paolo ; Davis, Sheldon ; Dinh, Vinh ; Linardos, Giulia ; Rossi, Paolo ; Cotugno, Nicola ; Sitoe, Nadia ; Lain, Maria Grazia ; Pallikkuth, Suresh ; Sanna, Marco ; Vaz, Paula ; Pahwa, Savita ; de Armas, Lesley ; Rinaldi, Stefano

BACKGROUNDDespite 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.METHODS46 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.FINDINGSBaseline (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.INTERPRETATIONB-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.FUNDINGThis 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.

2022-09-01·Pediatric Infectious Disease Journal

Timing of Monovalent Vaccine Administration in Infants Receiving DTaP-based Combination Vaccines in the United States

Article

作者: Petigara, Tanaz ; Johnson, David ; Chen, Ya-Ting ; Goveia, Michelle G ; Wolfson, Lara ; Marshall, Gary S ; Liu, Zhiwen

Background:The recommended US infant immunization schedule includes doses of diphtheria, tetanus, acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) and hepatitis B virus (HepB) during the first 6 months of life. Little information is available about the timing of associated, complementary monovalent vaccine administration in infants receiving DTaP-based pentavalent combination vaccines.Methods:This was a retrospective cohort study of infants born between July 1, 2010, and June 30, 2018, in the US MarketScan commercial claims and encounters database. Descriptive statistics were used to assess vaccine administration patterns. Multivariate logistic regression was performed to explore factors associated with coadministration of DTaP-IPV/Hib and HepB.Results:Among infants who received DTaP-HepB-IPV (n = 129,885), 93.7% had claims for at least 2 Hib doses; most (91.5%‐98.3%) of these doses were administered on the same day as DTaP-HepB-IPV doses. Among infants who received DTaP-IPV/Hib (n=214,172), 95.3% had claims for ≥2 doses of HepB. Although coverage was high, 59.2% received the second HepB dose on the same day as the first DTaP-IPV/Hib dose, and 44.6% received the third dose of HepB on the same day as the third DTaP-IPV/Hib dose. Differences in coadministration of the second and third HepB doses with DTaP-IPV/Hib were associated with the region of residence, provider type, health plan type and coadministration of pneumococcal conjugate vaccine and rotavirus vaccine.Conclusions:Almost all infants received the appropriate, complementary monovalent vaccine series. However, this study found variability in the timing of HepB doses in relation to DTaP-IPV/Hib doses with many infants not completing the HepB series until 9 months of age.

2021-03-01·Vaccine3区 · 医学

Impact of maternal diphtheria-tetanus-acellular pertussis vaccination on pertussis booster immune responses in toddlers: Follow-up of a randomized trial

3区 · 医学

Article

作者: Nolan, Terry ; Tapiéro, Bruce ; Marchisio, Paola Giovanna ; Novas, Begoña Arias ; Palomino, Esperanza Escribano ; Vanderkooi, Otto G ; Kostanyan, Lusine ; Halperin, Scott A ; Janota, Jan ; García-Sicilia, José ; Amador, Jose Tomas Ramos ; Miranda-Valdivieso, Mariano ; Baca, Manuel ; Kosina, Pavel ; Bozensky, Jan ; Zuccotti, Gian Vincenzo ; Meyer, Nadia ; Cheuvart, Brigitte ; Ortega, María José Cilleruelo ; Stranak, Zbynek ; Mesaros, Narcisa ; de la Cueva, Ignacio Salamanca ; Arribas, Jose M Merino ; Perrett, Kirsten P ; Ceregido, Maria Angeles ; Virta, Miia ; Kuriyakose, Sherine O ; Rumlarova, Sarka ; Martinón-Torres, Federico

BACKGROUNDTransplacentally transferred antibodies induced by maternal pertussis vaccination interfere with infant immune responses to pertussis primary vaccination. We evaluated whether this interference remains in toddlers after booster vaccination.METHODSIn a prior phase IV, observer-blind, placebo-controlled, randomized study (NCT02377349), pregnant women in Australia, Canada and Europe received intramuscular tetanus-reduced-antigen-content diphtheria-three-component acellular pertussis vaccine (Tdap group) or placebo (control group) at 27^0/7-36^6/7 weeks' gestation, with crossover immunization postpartum. Their infants were primed (study NCT02422264) and boosted (at 11-18 months; current study NCT02853929) with diphtheria-tetanus-three-component acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTaP-HepB-IPV/Hib) and 13-valent pneumococcal conjugate vaccine. Immunogenicity before and after booster vaccination, and reactogenicity and safety of the booster were evaluated descriptively.RESULTS263 (Tdap group) and 277 (control group) toddlers received a DTaP-HepB-IPV/Hib booster. Pre-booster vaccination, observed geometric mean concentrations (GMCs) for the three pertussis antigens and diphtheria were 1.4-1.5-fold higher in controls than in the Tdap group. No differences were observed for the other DTaP-HepB-IPV/Hib antigens. One month post-booster vaccination, booster response rates for pertussis antigens were ≥ 92.1% and seroprotection rates for the other DTaP-HepB-IPV/Hib antigens were ≥ 99.2% in both groups (primary objective). Higher post-booster GMCs were observed in controls versus the Tdap group for anti-filamentous hemagglutinin (1.2-fold), anti-pertussis toxoid (1.5-fold) and anti-diphtheria (1.4-fold). GMCs for the other DTaP-HepB-IPV/Hib antigens were similar between groups. Serious adverse events were reported for three toddlers (controls, not vaccination-related). One death occurred pre-booster (Tdap group, not vaccination-related).CONCLUSIONSAs a consequence of interference of maternal pertussis antibodies with infant immune responses to pertussis primary vaccination, pertussis antibody concentrations were still lower in toddlers from Tdap-vaccinated mothers before DTaP-HepB-IPV/Hib booster vaccination. After the booster, antibody concentrations were lower for filamentous hemagglutinin and pertussis toxoid but not for pertactin. The clinical significance of this interference requires further evaluation.CLINICAL TRIAL REGISTRATIONClinicalTrials.gov: NCT02853929.

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