title: Vaccine platform for prevention of tuberculosis and mother-to-child transmission of human immunodeficiency virus type 1 through breastfeeding.
abstract: Most children in Africa receive their vaccine against tuberculosis at birth. Those infants born to human immunodeficiency virus type 1 (HIV-1)-positive mothers are at high risk of acquiring HIV-1 infection through breastfeeding in the first weeks of their lives. Thus, the development of a vaccine which would protect newborns against both of these major global killers is a logical yet highly scientifically, ethically, and practically challenging aim. Here, a recombinant lysine auxotroph of Mycobacterium bovis bacillus Calmette-Guérin (BCG), a BCG strain that is safer than those currently used and expresses an African HIV-1 clade-derived immunogen, was generated and shown to be stable and to induce durable, high-quality HIV-1-specific CD4(+)- and CD8(+)-T-cell responses. Furthermore, when the recombinant BCG vaccine was used in a priming-boosting regimen with heterologous components, the HIV-1-specific responses provided protection against surrogate virus challenge, and the recombinant BCG vaccine alone protected against aerosol challenge with M. tuberculosis. Thus, inserting an HIV-1-derived immunogen into the scheduled BCG vaccine delivered at or soon after birth may prime HIV-1-specific responses, which can be boosted by natural exposure to HIV-1 in the breast milk and/or by a heterologous vaccine such as recombinant modified vaccinia virus Ankara delivering the same immunogen, and decrease mother-to-child transmission of HIV-1 during breastfeeding.
authors.affiliation: Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom.
authors.forename: Eung-Jun
authors.initials: EJ
authors.lastname: Im
authors.forename: Narcís
authors.initials: N
authors.lastname: Saubi
authors.forename: Goretti
authors.initials: G
authors.lastname: Virgili
authors.forename: Clare
authors.initials: C
authors.lastname: Sander
authors.forename: Denise
authors.initials: D
authors.lastname: Teoh
authors.forename: Jose M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
authors.forename: Joan
authors.initials: J
authors.lastname: Joseph
authors.forename: Tomás
authors.initials: T
authors.lastname: Hanke
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology; D001942:Breast Feeding; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D001428:Bacterial Vaccines; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic