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A single birth dose of Hepatitis B vaccine induces polyfunctional CD4⁺ T helper cells.

ABSTRACT: A single birth-dose of Hepatitis B vaccine (HepB) can protect newborns from acquiring Hepatitis B infection through vertical transmission, though several follow-up doses are required to induce long-lived protection. In addition to stimulating antibodies, a birth-dose of HepB might also induce polyfunctional CD4⁺ T-cells, which may contribute to initial protection. We investigated whether vaccination with HepB in the first week of life induced detectable antigen-specific CD4⁺ T-cells after only a single dose and following completion of the entire HepB vaccine schedule (3 doses). Using HBsAg- stimulated peripheral blood mononuclear cells from 344 infants, we detected increased populations of antigen-specific polyfunctional CD154⁺IL-2⁺TNFα⁺ CD4⁺ T-cells following a single birth-dose of HepB in a proportion of infants. Frequencies of polyfunctional T-cells increased following the completion of the HepB schedule but increases in the proportion of responders as compared to following only one dose was marginal. Polyfunctional T-cells correlated positively with serum antibody titres following the birth dose (day30) and completion of the 3-dose primary HepB vaccine series (day 128). These data indicate that a single birth dose of HepB provides immune priming for both antigen-specific B- and T cells.

SUBMITTER: Strandmark J

PROVIDER: S-EPMC9681035 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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A single birth dose of Hepatitis B vaccine induces polyfunctional CD4+ T helper cells.

Strandmark Julia J Darboe Alansana A Diray-Arce Joann J Ben-Othman Rym R Vignolo Sofia M SM Rao Shun S Smolen Kinga K KK Leroux-Roels Geert G Idoko Olubukola T OT Sanchez-Schmitz Guzmán G Ozonoff Al A Levy Ofer O Kollmann Tobias R TR Marchant Arnaud A Kampmann Beate B

Frontiers in immunology 20221108

A single birth-dose of Hepatitis B vaccine (HepB) can protect newborns from acquiring Hepatitis B infection through vertical transmission, though several follow-up doses are required to induce long-lived protection. In addition to stimulating antibodies, a birth-dose of HepB might also induce polyfunctional CD4+ T-cells, which may contribute to initial protection. We investigated whether vaccination with HepB in the first week of life induced detectable antigen-specific CD4+</sup ...[more]

PMID: 36426360

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Project description:BackgroundThis phase I/II partially blinded, randomized, dose-ranging study assessed the safety and immunogenicity of a novel human immunodeficiency virus type 1 (HIV-1) vaccine candidate consisting of a recombinant fusion protein (F4) containing 4 HIV-1 clade B antigens (Gag p24, Pol reverse transcriptase, Nef, and Gag p17) adjuvanted with AS01 in HIV-seronegative volunteers. Methods. Two doses of the recombinant F4 protein (10, 30, or 90 μg/dose), adjuvanted with AS01 or reconstituted with water for injection, were administered 1 month apart to 180 healthy volunteers aged 18-40 years. F4-specific CD4(+) T cell responses were measured using intracellular cytokine staining after in vitro stimulation by overlapping peptide pools covering the 4 individual antigens. Results. Reactogenicity was higher during the 7-day period after each vaccine dose in the adjuvanted than in the nonadjuvanted groups. In the adjuvanted groups, the overall immune response rate was high after the second vaccine dose, with highest responder rates seen in the 10-μg F4/AS01 group (100% to 3 HIV-1 antigens and 80% to all 4 HIV-1 antigens). High and long-lasting CD4(+) T cell frequencies were observed (up to a median value of 1.2% F4-specific CD4(+) T cells at day 44), with strongest responses directed against reverse transcriptase. Antigen-specific CD4(+) T cells exhibited a polyfunctional phenotype, expressing at least CD40 ligand and interleukin 2, often in combination with tumor necrosis factor α and/or interferon γ. Vaccine-induced CD4(+) T cell responses were broadly cross-reactive to all 4 antigens derived from HIV-1 clades A and C. Conclusions. These results support further clinical investigation of this HIV-1 vaccine candidate both in a prophylactic setting (alone, in conjunction with an envelope-based antigen or in combination with other vaccine approaches in a heterologous prime-boost regimen) and as a potentially disease-modifying therapeutic vaccine in HIV-1-infected subjects.Clinical trials registrationNCT00434512.

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A single birth dose of Hepatitis B vaccine induces polyfunctional CD4⁺ T helper cells.

Publications

A single birth dose of Hepatitis B vaccine induces polyfunctional CD4<sup>+</sup> T helper cells.

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