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Multi-subtype gp160 DNA immunization induces broadly neutralizing anti-HIV antibodies

Gene Therapy volume 11, pages 1146–1154 (2004)Cite this article

Abstract

A highly desirable feature for an human immunodeficiency virus type 1 (HIV-1) vaccine is the ability to induce broadly reactive anti-envelope antibodies that can neutralize primary HIV-1 isolates. Two immunizations with an HIV-1 envelope-encoding plasmid together with recombinant granulocyte–macrophage colony-stimulating factor (rGM-CSF) resulted in high antibody titers in mice. The antibody induction was further enhanced after immunization with genes encoding HIV-1 envelopes originating from subtypes A, B and C. The sera from these animals were able to neutralize A, B and C viral isolates, whereas the sera from animals immunized solely with subtype B DNA neutralized only subtype B virus. The combined DNA vaccine gave serum antibodies with broad recognition of HIV-1 envelope epitopes as determined by peptide mapping. Cell-mediated immunity was not compromised by the increased humoral immunity. This demonstrates the ability of multiple envelope genes to induce the desired antibody response against several subtypes. Moreover, it documents the ability of rGM-CSF to enhance the potency of such a vaccine when given simultaneously. The strategy may be useful for making an HIV vaccine more potent and broadly effective against strains of different clades.

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Acknowledgements

We thank Reinhold Benthin and Gunnel Engström for outstanding technical assistance and Roya Hakimnia, Sayi Kimwaga-Stika, Sandra Melki and Marwa Osman for the gp41 ELISA. This work was supported by the Foundation for Strategic Research: the Infection and Vaccinology programme and the Inflammation programme; and by the Swedish Research Council and EU Grant ICA4-CT-2002-10036.

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Authors and Affiliations

  1. Department of Virology, Swedish Institute for Infectious Disease Control and Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden

    E Rollman, J Hinkula, B Zuber, A Kjerrström, M Liu, B Wahren & K Ljungberg

  2. Department of Medicine, Clinical Research Center, Huddinge Hospital, Karolinska Institutet, Stockholm, Sweden

    J Arteaga

  3. Transgene, Strasbourg, France

    M Liu

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  1. E Rollman
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Rollman, E., Hinkula, J., Arteaga, J. et al. Multi-subtype gp160 DNA immunization induces broadly neutralizing anti-HIV antibodies. Gene Ther 11, 1146–1154 (2004). https://doi.org/10.1038/sj.gt.3302275

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