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Journal of Virology, September 2007, p. 9408-9418, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00707-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vaccine Platform for Prevention of Tuberculosis and Mother-to-Child Transmission of Human Immunodeficiency Virus Type 1 through Breastfeeding{triangledown}

Eung-Jun Im,1 Narcís Saubi,2 Goretti Virgili,2 Clare Sander,3 Denise Teoh,1 Jose M. Gatell,2 Helen McShane,3 Joan Joseph,2,{dagger} and Tomás Hanke1,{dagger}*

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe, Oxford OX3 9DS, United Kingdom,1 Catalan HIV Vaccine Research and Development Center, AIDS Research Unit, Infectious Diseases Department, Hospital Clinic, August Pi i Sunyer Biomedical Research Institute, School of Medicine, University of Barcelona, 170 08036 Barcelona, Spain,2 Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford OX3 7LJ, United Kingdom3

Received 3 April 2007/ Accepted 11 June 2007

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.

* Corresponding author. Mailing address: Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford OX3 9DS, United Kingdom. Phone: 44 1865 222355. Fax: 44 1865 222502. E-mail: tomas.hanke{at}imm.ox.ac.uk

{triangledown} Published ahead of print on 27 June 2007.

{dagger} These authors have codirected the research work and have contributed equally to this work.

Journal of Virology, September 2007, p. 9408-9418, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.00707-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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