Robust immune response elicited by a novel and unique Mycobacterium tuberculosis protein using an optimized DNA/protein heterologous prime/boost protocol

• Published in: Immunology 2012-03, Vol.135 (3), p.216-225
• Main Authors: Cayabyab, Mark J., Kashino, Suely S., Campos‐Neto, Antonio
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Animals; Antibodies, Bacterial - biosynthesis; Antigens, Bacterial - administration & dosage; Antigens, Bacterial - genetics; Bacterial Proteins - administration & dosage; Bacterial Proteins - genetics; Bacterial Proteins - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; DNA, Bacterial - administration & dosage; DNA, Bacterial - genetics; Female; Immunization, Secondary; Immunoglobulin G - biosynthesis; Interferon-gamma - biosynthesis; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Original; prime/boost; Toll-Like Receptor 4 - agonists; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - genetics; vaccine; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, Synthetic - administration & dosage
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/j.1365-2567.2011.03525.x

Summary An efficacious tuberculosis (TB) vaccine will probably need to induce both CD4 and CD8 T‐cell responses specific to a protective Mycobacterium tuberculosis antigen(s). To achieve this broad cellular immune response we tested a heterologous DNA/protein combination vaccine strategy. We used a purified recombinant protein preparation of a unique M. tuberculosis antigen (rMT1721) found in the urine of TB patients, an optimized plasmid DNA expressing this protein (DNA‐MT1721), and a Toll‐like receptor 4 agonist adjuvant. We found that priming mice with DNA‐MT1721 and subsequently boosting with rMT1721 elicited high titres of specific IgG1 and IgG2a antibodies as well as high magnitude and polyfunctional CD4+ T‐cell responses. However, no detectable CD8+ T‐cell response was observed using this regimen of immunization. In contrast, both CD4+ and CD8+ T‐cell responses were detected after a prime/boost vaccination regimen using rMT1721 as the priming antigen and DNA‐MT1721 as the boosting immunogen. These findings support the exploration of heterologous DNA/protein immunization strategies in vaccine development against TB and possibly other infectious diseases.