Subunit Protein Vaccine Delivery System for Tuberculosis Based on Hepatitis B Virus Core VLP (HBc-VLP) Particles
Despite the development of modern medicine, tuberculosis (TB), caused by the pathogenic bacterium, Mycobacterium tuberculosis (Mtb), remains one of the deadliest diseases. This bacterium can lay dormant in individuals and get activated when immunity goes
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Introduction Tuberculosis (TB) is the second leading infectious disease by mortality rate. The disease is caused by the bacterium Mycobacterium tuberculosis (Mtb). TB primarily affects the respiratory system resulting in Pulmonary Tuberculosis, but it has also extrapulmonary targets. According to latest estimates, globally 9.0 million new cases are reported annually and 1.5 million deaths due to TB were reported in 2013 alone. TB is prevalent across the globe with South-East Asia and Western Pacific Regions accounting for 56 % of the cases and the African region contributing another quarter. Among different nations, India and China have the largest number of disease cases [1]. Mtb is characterized by slow growth, complex cell envelope, intracellular pathogenesis, slow generation time (~24 h for the organism in synthetic medium or in infected animals) and has a striking dormancy profile. The bacterial genome of 4.41 Mb base pairs has an uncharacteristically high GC (Guanine + Cytosine) content (~65.9 %) and encodes about 4015 genes [2]. The disease transmission is mainly by inhalation of aerosol containing bacteria which originates from the expectoration of affected individuals. The entry of the bacterium into the human body is mostly by respiratory route and in case of severe infection it can spread to other parts of the body via lymphatic system or blood. About 15 % of patients develop extrapulmonary TB of pleura, lymphatics, bone, genitourinary system, meninges, peritoneum, or skin [3]. Bacille Calmette-Guerin (BCG) has been the only available vaccine for TB for nearly one century but has many drawbacks. As the efficacy of BCG has been shown to vary from zero to 80 %, the
Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_26, © Springer Science+Business Media New York 2016
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emergence of new and dangerous drug resistant bacteria, calls for urgent measures to find new vaccines. Obviously the availability of an affordable vaccine could help to eliminate the disease burden globally [4]. Even though there have been many ideas to develop new vaccines, most strategies involve mixing more than one selected antigen/epitope from a pathogen and using it as a vaccine. Due to the presence of several antigenic epitopes, these vaccines are expected to generate greater protection when compared to a single antigen. Several putative protective antigens have been identified from Mycobacterium tuberculosis (Mtb), the bacteria that cause TB [5, 6]. This type of vaccine where recombinant protein subunit comprising multiple open reading frames strung together is both simple and cost effective and these fusion vaccines can be more immunogenic than the individual components. Such hybrid protein vaccines consisting of mycobacterial proteins such as Mtb39 and Mtb32 (Mtb72F), or Ag85B and ESAT-6 (Hybrid-1) [7], the polyprotein of ESAT-6 and Ag85A have shown to be promising
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