Research and development of new tuberculosis vaccines: a review

Abstract

Tuberculosis kills more people worldwide than any other single infectious disease agent, a threat made more dire by the spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). Development of new vaccines capable of preventing TB disease and new Mtb infection are an essential component of the strategy to combat the TB epidemic. Accordingly, the WHO considers the development of new TB vaccines a major public health priority. In October 2017, the WHO convened a consultation with global leaders in the TB vaccine development field to emphasize the WHO commitment to this effort and to facilitate creative approaches to the discovery and development of TB vaccine candidates. This review summarizes the presentations at this consultation, updated with scientific literature references, and includes discussions of the public health need for a TB vaccine; the status of efforts to develop vaccines to replace or potentiate BCG in infants and develop new TB vaccines for adolescents and adults; strategies being employed to diversify vaccine platforms; and new animal models being developed to facilitate TB vaccine development. A perspective on the status of these efforts from the major funders and organizational contributors also is included. This presentation highlights the extraordinary progress being made to develop new TB vaccines and provided a clear picture of the exciting development pathways that are being explored.

PE_PGRS33, an Important Virulence Factor of Mycobacterium tuberculosis and Potential Target of Host Humoral Immune Response

“…Ambitious goals for better controlling the global TB epidemic can be met with the development of new drug treatments, improved diagnostics, and most importantly the availability of a new and more effective vaccine [1,2]. At present, and 100 years after its introduction, Mycobacterium bovis Bacille Calmette and Guérin (BCG) is the only vaccine available for TB control [13,14], though its protective activity in preventing TB in adults is variable, incomplete, and overall insufficient [15][16][17]. There is an urgent need for a new and more effective vaccine, yet poor understanding of the complex relationship between Mtb and the human immune system, paired with the lack of immunological correlates of protection, makes this endeavor challenging [18].…”

Recent Advances in the Development of Protein- and Peptide-Based Subunit Vaccines against Tuberculosis

“…Children show lower rates of TB notifications, lower proportions of smear-positive pulmonary TB, and, consequently, they exhibited a smaller contribution to TB transmission [ 29 ]. Therefore, adolescents and adults should be defined as a priority strategic target as they represent the leading source of Mtb dissemination [ 9 , 30 , 31 ].…”

“…While Mtb is a complex microorganism, composed of approximately 4000 genes, the selection of a small number of antigens among them is complicated because of the limited knowledge about the function of several antigens and their differential expression at different stages of the pathogen life cycle [ 31 , 38 ]. Moreover, Mtb escape mechanisms, as the downregulation of antigen processing and presentation, have made the identification procedure more difficult, resulting in the current lack of stringent immunological markers as correlates of protection [ 38 , 39 ].…”

Harnessing the Immunomodulatory Properties of Bacterial Ghosts to Boost the Anti-mycobacterial Protective Immunity

“…Many factors contribute to the high burden of disease including poverty, HIV co-infection, limited vaccine efficacy and drug resistance (2, 3). As the development of vaccines with improved protective efficacy (4) and drugs with novel modes of action (5) has proven to be challenging and expensive, alternative solutions are urgently needed.…”