The quest for vaccine-induced immune correlates of protection against tuberculosis

Abstract

Immunization strategies against tuberculosis (TB) that confer better protection than neonatal vaccination with the 101-year-old Bacille Calmette-Guerin (BCG) are urgently needed to control the epidemic, but clinical development is hampered by a lack of established immune correlates of protection (CoPs). Two phase 2b clinical trials offer the first opportunity to discover human CoPs against TB. Adolescent BCG re-vaccination showed partial protection against Mycobacterium tuberculosis ( Mtb) infection, as measured by sustained IFNγ release assay (IGRA) conversion. Adult M72/AS01 E vaccination showed partial protection against pulmonary TB. We describe two collaborative research programs to discover CoPs against TB and ensure rigorous, streamlined use of available samples, involving international immunology experts in TB and state-of-the-art technologies, sponsors and funders. Hypotheses covering immune responses thought to be important in protection against TB have been defined and prioritized. A statistical framework to integrate the data analysis strategy was developed. Exploratory analyses will be performed to generate novel hypotheses.

Qualification of the differential leukocyte count and immunophenotyping in cryopreserved ex vivo whole blood assay

“…edctp.org/international-partnerships-against-infectious-diseases/portb). Analysis of these samples with the DLC-ICE assay offers an invaluable opportunity to identify correlates of protection against tuberculosis in humans [22].…”

“…The DLC‐ICE method will also be used in stored blood samples of participants in the ongoing Prevention of Tuberculosis Recurrence (POR‐TB) trial evaluating the H56:IC31 vaccine (https://www.porconsortium.org/; https://publications.edctp.org/international-partnerships-against-infectious-diseases/por-tb). Analysis of these samples with the DLC‐ICE assay offers an invaluable opportunity to identify correlates of protection against tuberculosis in humans [22].…”

Challenges in TB research

“…Despite years of research toward correlate of vaccine protection discovery, such markers remain elusive. However, a major international effort using samples from the recent proof-of-concept trials is underway ( Nemes et al, 2022 ).…”

OMIP‐101: 27‐color flow cytometry panel for immunophenotyping of major leukocyte populations in fixed whole blood

“…We developed this antibody panel in the context of a research program that aims to identify vaccine‐induced immune correlates of protection against Mycobacterium tuberculosis infection or TB disease [1]. The panel was designed to enumerate and phenotype relevant leukocyte subsets that may be modulated by vaccination in fixed whole blood samples collected from participants enrolled in large TB vaccine clinical trials.…”