Tuberculosis Basic Research

NIAID supports basic research on Mycobacterium tuberculosis (Mtb), the causative agent of TB, and seeks to understand how the bacterium causes disease in humans. The Institute is accelerating efforts to identify new candidate drugs, vaccines and biomarkers and technologies with diagnostic potential to improve TB diagnosis, treatment, and prevention strategies.

METAGENOTE

METAGENOTE will be retired on May 1, 2025

After this date, you will no longer have access to the application or your data through the interface. Following its retirement, the METAGENOTE code, documentation, and more information will be available at https://github.com/niaid/metagenote.

Vaccine Adjuvant Discovery and Mechanistic Research

scientist at a microscope
Credit: NIAID

The availability of a wide range of adjuvants facilitates the rational pairing of antigen and adjuvant to maximize vaccine efficacy, but also allows vaccines to be optimized for their target population, such as vaccines for the elderly or newborns.

Innate immune receptors and signaling pathways associated with the activation of immune cells continue to be discovered, representing potentially novel targets for vaccine adjuvants. In addition to using natural immunostimulatory compounds (eg. Lipid A) or their derivatives (eg. INI-2004) as adjuvants, small molecule agonists of innate immune receptors (eg. combination adjuvant Fos47) and other targets are increasingly used in place of the larger and more complex naturally occurring immunostimulators, making large drug libraries attractive targets for screening to identify novel adjuvants. Adjuvant discovery is further aided by the increasing use of in silico screening approaches, and research into the mechanism of action regarding aspects such as the target molecule, binding site on the target molecule, or the downstream signaling triggered by the binding.

Adjuvant discovery and mechanistic research is supported by the NIAID under three main mechanisms:

Several adjuvants that resulted from NIAID adjuvant discovery grants and contracts are accessible through the NIAID Vaccine Adjuvant Compendium (VAC).

Featured Research

Vaccine Adjuvant Compendium (VAC)

Production of Adjuvant Mimics and Small Business Innovation Research

Many experimental and licensed vaccines depend on adjuvants to exert their protective effect. While several immunostimulatory compounds and formulations are available commercially for use in preclinical studies, these compounds generally cannot be advanced into clinical trials. Furthermore, head-to-head comparisons of novel experimental and existing adjuvants is hampered by limited availability of such reagents.

Adjuvant Development Program

Currently, for infectious diseases, five adjuvants have been used in vaccines licensed in the United States (U.S.): Aluminum hydroxide/aluminum phosphate; AS04, which consists of 4’-monophosphoryl lipid A (MPL) and aluminum hydroxide; AS01B, a liposomal formulation of MPL and QS-21; MF59, an oil-in-water emulsion; and CpG 1018, a CpG Oligodinucleotide.

Advancing Vaccine Adjuvant Research for Tuberculosis (AVAR-T)

A successful tuberculosis (TB) vaccine would have a major impact on morbidity and mortality associated with TB, and on global TB control. However, vaccine strategies have fallen short due to limited understanding of the types of Mycobacterium tuberculosis (Mtb) immunogens that induce long-term protective immunity. The design of an efficacious TB vaccine will also likely require formulation with appropriate vaccine adjuvants.

Adjuvant Comparison & Characterization (ACC)

Numerous vaccine adjuvants are currently in development; however, the rational selection of adjuvants for specific vaccines is hindered by a lack of insights from formal side-by-side comparisons of adjuvants that include the creation of comprehensive immunological profiles.

Investigator-initiated Vaccine Adjuvant Research

Vaccine adjuvant researchers are invited to submit research proposals in response to NIAID’s parent announcements for R-type grants. Most projects submitted through the parent grant mechanisms focus on adjuvant mechanisms-of-action and early adjuvant development studies, as well as basic immunology studies that support the basis of adjuvant discovery and development, both efforts that are supported by NIAID through solicited programs.

Contact Information

Ari Joffe

Molecular Mechanism of Combination Adjuvants (MMCA)

Live-attenuated vaccines contain a wide variety of immune agonists and can provide durable protection, sometimes following a single immunization. Subunit antigen vaccines, however, generally lack immune stimulators and require the addition of exogenous adjuvants to induce protective immunity. A deeper understanding of the mechanisms underlying synergistic enhancement by combinations of adjuvants could recapitulate the immune stimulating properties of live-attenuated vaccines in a rational and controlled way.

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