Role of Fused Mycobacterium tuberculosis Immunogens and Adjuvants in Modern Tuberculosis Vaccines

Abstract

Several approaches have been developed to improve or replace the only available vaccine for tuberculosis (TB), BCG (Bacille Calmette Guerin). The development of subunit protein vaccines is a promising strategy because it combines specificity and safety. In addition, subunit protein vaccines can be designed to have selected immune epitopes associated with immunomodulating components to drive the appropriate immune response. However, the limited antigens present in subunit vaccines reduce their capacity to stimulate a complete immune response compared with vaccines composed of live attenuated or killed microorganisms. This deficiency can be compensated by the incorporation of adjuvants in the vaccine formulation. The fusion of adjuvants with Mycobacterium tuberculosis (Mtb) proteins or immune epitopes has the potential to become the new frontier in the TB vaccine development field. Researchers have addressed this approach by fusing the immune epitopes of their vaccines with molecules such as interleukins, lipids, lipoproteins, and immune stimulatory peptides, which have the potential to enhance the immune response. The fused molecules are being tested as subunit vaccines alone or within live attenuated vector contexts. Therefore, the objectives of this review are to discuss the association of Mtb fusion proteins with adjuvants; Mtb immunogens fused with adjuvants; and cytokine fusion with Mtb proteins and live recombinant vectors expressing cytokines. The incorporation of adjuvant molecules in a vaccine can be complex, and developing a stable fusion with proteins is a challenging task. Overall, the fusion of adjuvants with Mtb epitopes, despite the limited number of studies, is a promising field in vaccine development.

Preliminary Studies on a Derivative Verotoxin as Oral Adjuvant

“…The main obstacle is to reach the inductive sites of the gut and to break the natural immune tolerance of those mucosal sites. This challenge may be overcome by using adjuvants [29]. Bacterial toxoids, such as CT and LT have been used as oral adjuvants for 20 years.…”

BCG Vaccine and New Approaches Against Prevention

“…RD1, 9.5 kb bir DNA parçası olup, diğer tüm BCG suşlarında delesyona uğramıştır, ESAT-6, CFP-10, Rv3873 ve diğerleri arasında PPE protein gibi T-lenfosit epitopları kodlar (11) ; RD2, Mpt64 ve CFP-21 (10) içeren bir çok proteinleri kodlayan 10.7 kb DNA segmentidir; RD14, PE-PGRS ve Rv1771 aileleri (gulonolakton dehidrojenaz) kodlayan bir DNA parçası olup, 9.1 kb'dır (12) . RD16, koloni morfolojik özellikleri ve hücre membran oluşumundan sorumlu olan Rv3405 kodlayan bir 7.6 kb DNA parça-sıdır (13) ve nRD18, genler, alternatif RNA polimeraz sigma faktörü kodlayan 1.5 kb parça içeren eden SigI'dir.…”

Immune responses elicited by the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis in mice

“…Th1-type cellular immunity, especially interferon-gamma (IFN-γ) and interleukin 12 (IL-12) cytokines, plays an important role in the resistance against TB [12,13]. Adjuvants used for the development of subunit vaccines can direct the type of immune response.…”