An experimental vaccine, called ID93, developed by scientists at the Infectious Disease Research Institute (IDRI) in Seattle, has advanced to phase 2 clinical testing.
The TB vaccine candidate combines ID93, a fusion of 4 mycobacterium tuberculosis antigens with diverse roles in pathogenesis, with the adjuvant GLA-SE, a synthetic toll-like receptor 4 (TLR4) agonist, formulated in a squalene oil and water nano-emulsion that has a significant safety track record.
“The four antigens representing different families of mycobacterium tuberculosis (MTB) proteins have been shown to be recognised in MTB-exposed individuals. RV1813 is a conserved hypothetical protein that is upregulated under hypoxic growth and predicted to be localised in the outer membrane. RV2608 (PPE42) is a probable outer membrane-associated PPE (pro-pro-glu motif-containing) protein. RV3619 (ESXV) and RV3620 (ESXW) are secreted proteins belonging to the ESAT-6 family of virulence factors,» says Rhea Coler, Senior. Vice President, Preclinical & Translational Science at IDRI.
Explaining the role of the adjuvant, Coler said, GLA-SE skews the immune response to a TH1 type immune response with induction of CD4+ T cells. Human immune correlates of protection against TB have not yet been identified. T-helper 1 (TH1) type cellular immunity is known to be crucial for controlling MTB infection and thus vaccine strategies aim to elicit these subsets.
Recently, studies have shown evidence that antibodies may also contribute to controlling disease in latently infected individuals.
Pre-clinical studies using mice, guinea pigs and non-human primates, have shown that ID93+GLA-SE is efficacious prophylactically as well as therapeutically. The vaccine significantly improved TB treatment outcomes over antibiotics alone and allowed the duration of antibiotic treatment to be reduced by 30%.
Therapeutic efficacy of ID93+GLA-SE is associated with enhanced TH1 responses, improved MTB clearance, and reduced pulmonary inflammation. “In mice and humans, we have observed immune responses 6-12 months after immunization,’’ Coler adds.
As a part of the efforts to make the vaccine affordable for those who need it, IDRI is planning to transfer the technology involved in the production of the vaccine to 3 different facilities in Africa and Asia.