Unbound MEDLINE

A novel tuberculosis DNA vaccine in an HIV-1 p24 protein backbone confers protection against Mycobacterium tuberculosis and simultaneously elicits robust humoral and cellular responses to HIV-1.

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major infectious disease worldwide. Moreover, latent M. tuberculosis infection is more likely to progress to active TB and eventually leads to death when HIV infection is involved. Thus, it is urgent to develop a novel TB vaccine with immunogenicity to both M. tuberculosis and HIV. In this study, four uncharacterized T cell epitopes from MPT64, Ag85A, Ag85B, and TB10.4 antigens of M. tuberculosis were predicted, and HIV-1-derived p24, an immunodominant protein that can induce protective responses to HIV-1, was used as an immunogenic backbone. M. tuberculosis epitopes were incorporated separately into the gene backbone of p24, forming a pP24-Mtb DNA vaccine. We demonstrated that pP24-Mtb immunization induced a strong M. tuberculosis-specific cellular response as evidenced by T cell proliferation, cytotoxicity, and elevated frequency of gamma interferon (IFN-γ)-secreting T cells. Interestingly, a p24-specific cellular response and high levels of p24-specific IgG were also induced by pP24-Mtb immunization. When the protective effect was assessed after mycobacterial challenge, pP24-Mtb vaccination significantly reduced tissue bacterial loads and profoundly attenuated the mycobacterial infection-related lung inflammation and injury. Our findings demonstrated that the pP24-Mtb tuberculosis vaccine confers effective protection against mycobacterial challenge with simultaneously elicited robust immune responses to HIV-1, which may provide clues for developing novel vaccines to prevent dual infections.

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  • Authors

    Li X, Xu W, Xiong S

    Source

    Clinical and vaccine immunology : CVI 19:5 2012 May pg 723-30

    MeSH

    AIDS Vaccines
    Acquired Immunodeficiency Syndrome
    Animals
    Antigens, Bacterial
    Bacterial Load
    Cell Proliferation
    Cytotoxicity Tests, Immunologic
    Disease Models, Animal
    Epitopes
    Female
    HIV Antibodies
    HIV Core Protein p24
    Humans
    Interferon-gamma
    Lung
    Mice
    Mice, Inbred BALB C
    Mycobacterium tuberculosis
    T-Lymphocytes
    Tuberculosis
    Tuberculosis Vaccines
    Vaccines, DNA

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22461526