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Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent mycobacterium tuberculosis infection
Institution:1. Division of Tuberculosis Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China;2. Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China;3. Centre for Biologicals Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario, Canada;1. State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Chinese Center for Disease Control and Prevention, Beijing, China;2. State Key Laboratory of Agrobiotechnology, Department of Microbiology and Immunology, College of Biological Sciences, China Agricultural University, Beijing 100193, China;3. Beijing Center for Diseases Prevention and Control, Beijing 100013, China;1. St George’s Medical School, University of London, London SW17 0RE, UK;2. Lionex GmbH, Braunschweig, Germany;3. Karolinska Institute, Stockholm, Sweden;1. School of Health Sciences (PPSK), Universiti Sains Malaysia (USM), 16150 Kubang Kerian, Kelantan, Malaysia;2. Rutgers New Jersey Medical School, Public Health Research Institute, Newark, NJ, USA;3. Department of Biomedical Sciences and Therapeutic, Faculty of Medicine and Health Sciences (FPSK), Universiti Malaysia Sabah (UMS), Sabah, Malaysia;4. Institute of Biotechnology, INTA, Buenos Aires, Argentina;5. Finlay Institute of Vaccines, La Habana, Cuba;1. Animal Biosafety Level III Laboratory at the Center for Animal Experiment, Wuhan University School of Medicine, Wuhan, Hubei, PR China;2. Aeras, Rockville, MD, USA;3. Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA
Abstract:The high global burden of tuberculosis (TB) underscores the urgent need for an effective TB vaccine since the only licensed Bacillus Calmette-Guérin (BCG) vaccine is ineffective in preventing adult pulmonary TB and affords no protection against latent TB infection (LTBI). Herein we investigated the potential of Mycobacterium tuberculosis (Mtb) antigen proteins AEC comprised of Ag85b and ESAT6-CFP10 proteins in conjunction with aluminum (Al) and polyriboinosinic-polyribocytidylic acid (poly-IC) as a novel subunit vaccine against TB. The immunogenicity and protection induced by the adjuvanted vaccine were evaluated in two animal models. Mice vaccinated with AEC/Al/poly-IC exhibited significant antigen-specific humoral immune responses and cell-mediated immunity as determined by immunoassay and multicolor flow cytometric assay, and the protective effect of the vaccine was demonstrated in a guinea pig model of latent Mtb infection. Compared to the control group, the mean pathological scores and bacterial loads in lungs and spleens of AEC/Al/poly-IC-immunized guinea pigs were significantly reduced. These data indicate that the AEC/Al/poly-IC is highly immunogenic in mice and can effectively protect guinea pigs against latent Mtb infection; it may represent a promising candidate vaccine for the control of latent TB.
Keywords:Mycobacterium tuberculosis  Subunit vaccine  Adjuvant  Immunogenicity  Protective efficacy  Latent tuberculosis infection
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