Advancing Adjuvants for Mycobacterium tuberculosis Therapeutics

Abstract

Tuberculosis (TB) remains one of the leading causes of death worldwide due to a single infectious disease agent. BCG, the only licensed vaccine against TB, offers limited protection against pulmonary disease in children and adults. TB vaccine research has recently been reinvigorated by new data suggesting alternative administration of BCG induces protection and a subunit/adjuvant vaccine that provides close to 50% protection. These results demonstrate the need for generating adjuvants in order to develop the next generation of TB vaccines. However, development of TB-targeted adjuvants is lacking. To help meet this need, NIAID convened a workshop in 2020 titled “Advancing Vaccine Adjuvants for Mycobacterium tuberculosis Therapeutics”. In this review, we present the four areas identified in the workshop as necessary for advancing TB adjuvants: 1) correlates of protective immunity, 2) targeting specific immune cells, 3) immune evasion mechanisms, and 4) animal models. We will discuss each of these four areas in detail and summarize what is known and what we can advance on in order to help develop more efficacious TB vaccines.

Protective Efficacy and Immunogenicity of Rv0351/Rv3628 Subunit Vaccine Formulated in Different Adjuvants Against Mycobacterium tuberculosis Infection

“…QS21 which is constituents of MPQ adjuvant can cause lysosomal disruption resulting in Syk- and NLRP3 inflammasome-activation, which is responsible for promoting production of inflammatory cytokines and enhancing cross-presentation with CD8 + T cells ( 35 39 ). This property of QS21 acted in synergy with MPL, resulting in Th1-polarizing effects of AS01 adjuvant ( 40 ), as superior induction of Ag-specific Th1 responses was observed in the mice that received Rv0351/Rv3628-MPQ. Meanwhile, there was only difference in formulation between MP and MPS as liposome form or emulsion form, respectively.…”

Functions of exosomal non-coding RNAs to the infection with Mycobacterium tuberculosis

“…This regulation of host cell reactions allows bacteria to isolate vital host factors to meet their material and energy demand to facilitate intracellular survival ( 65 ). These steps may be managed by subversing host miRNA networks involved in the mediation of carbon, nitrogen and lipid metabolism in the infected cells ( 66 , 67 ).…”

Advances in protein subunit vaccines against tuberculosis

“…TB-specific adjuvants that induce a strong immune response in the lungs but minimize the corresponding tissue damage are ideal. In order to meet the needs of TB vaccine development, a workshop entitled "Vaccine Adjuvants for Advancing the treatment of Mycobacterium tuberculosis" was held in July 2020, and factors correlates of protective immunity, targeting specific immune cells, immune evasion mechanisms, and animal models were identified as four research areas critical to the development of optimal TB vaccine adjuvants (28). In recent years, a variety of novel adjuvants have been developed, and most available protein subunit vaccine adjuvants are based on Tolllike receptor (TLR) agonists and use liposomes and emulsions as delivery vehicles as shown in Table 1.…”