[HTML][HTML] The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: first-in-human trial

RN Coler, TA Day, R Ellis, FM Piazza, AM Beckmann… - npj Vaccines, 2018 - nature.com
RN Coler, TA Day, R Ellis, FM Piazza, AM Beckmann, J Vergara, T Rolf, L Lu, G Alter…
npj Vaccines, 2018nature.com
Tuberculosis (TB) is the leading cause of infectious death worldwide. Development of
improved TB vaccines that boost or replace BCG is a major global health goal. ID93+ GLA-
SE is a fusion protein TB vaccine candidate combined with the Toll-like Receptor 4 agonist
adjuvant, GLA-SE. We conducted a phase 1, randomized, double-blind, dose-escalation
clinical trial to evaluate two dose levels of the ID93 antigen, administered intramuscularly
alone or in combination with two dose levels of the GLA-SE adjuvant, in 60 BCG-naive …
Abstract
Tuberculosis (TB) is the leading cause of infectious death worldwide. Development of improved TB vaccines that boost or replace BCG is a major global health goal. ID93 + GLA-SE is a fusion protein TB vaccine candidate combined with the Toll-like Receptor 4 agonist adjuvant, GLA-SE. We conducted a phase 1, randomized, double-blind, dose-escalation clinical trial to evaluate two dose levels of the ID93 antigen, administered intramuscularly alone or in combination with two dose levels of the GLA-SE adjuvant, in 60 BCG-naive, QuantiFERON-negative, healthy adults in the US (ClinicalTrials.gov identifier: NCT01599897). When administered as 3 injections, 28 days apart, all dose levels of ID93 alone and ID93 + GLA-SE demonstrated an acceptable safety profile. All regimens elicited vaccine-specific humoral and cellular responses. Compared with ID93 alone, vaccination with ID93 + GLA-SE elicited higher titers of ID93-specific antibodies, a preferential increase in IgG1 and IgG3 subclasses, and a multifaceted Fc-mediated effector function response. The addition of GLA-SE also enhanced the magnitude and polyfunctional cytokine profile of CD4+ T cells. The data demonstrate an acceptable safety profile and indicate that the GLA-SE adjuvant drives a functional humoral and T-helper 1 type cellular response.
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