Novel Tuberculosis Shots May Benefit HIV-Positive Population

TOPLINE:

A two-dose regimen of the M72/AS01_E-4, a recombinant fusion protein tuberculosis vaccine candidate, demonstrated acceptable safety and immunogenicity in virally suppressed, antiretroviral therapy (ART)-treated adolescents and adults living with HIV, showing strong antibody and CD4 T-cell responses. 

METHODOLOGY:

• Researchers conducted a randomized, phase 2 trial in South Africa to evaluate the safety and immunogenicity of the investigational M72/AS01_E-4 tuberculosis vaccine, derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A) and AS01_E-4 adjuvant, in people living with HIV.
• Overall, 401 participants — each on ART for ≥ 3 months with HIV viral loads < 200 copies per mL and CD4 T-cell count ≥ 200 cells per µL — were randomly assigned to receive either the M72/AS01 vaccine (n = 201; mean age, 29.4 years; 87% women) or placebo (n = 200; mean age, 29.6 years; 88% women), on days 1 and 29.
• Primary endpoints were the vaccine’s reactogenicity and safety, assessed via solicited adverse events (AEs) within 7 days, unsolicited AEs within 28 days, and serious AEs throughout the trial.
• Immunogenicity was evaluated by measuring M72-specific immunoglobulin G antibody concentrations on days 1, 29, 57, 210, and 390, as well as M72-specific CD4 and CD8 T-cell responses.

TAKEAWAY:

• Vaccine-related AEs occurred more frequently in the vaccine group (12%) than in the placebo group (6%), primarily due to a higher rate of injection-site reactions in the vaccine group (8% vs 1%). Two severe unsolicited AEs related to the vaccine were reported — a case each of dizziness and injection-site erythema, but no participant discontinued the trial or died due to AEs.
• Nine serious AEs occurred — four in the vaccine group (COVID-19, tibia fracture, spontaneous abortion, or psychotic disorder) and five in the placebo group (COVID-19, anal abscess, spontaneous abortion, substance-induced psychotic disorder, or physical assault); none was related to the vaccine.
• In the vaccine group, the geometric mean concentration of antibodies against M72 increased from the baseline level to 13.28 EU/mL by day 29, peaked at 479.70 EU/mL by day 57, and then declined to 32.43 EU/mL by day 390 — yet remained above prevaccination levels. No such increase was observed in the placebo group.
• The M72-specific CD4 T cells expressing interferon gamma or interleukin-2 was significantly higher in the vaccine group than in the placebo group at both day 57 and day 390 (P < .0001).

IN PRACTICE:

“In conclusion, a two-dose regimen of M72/AS01_E-4 vaccine, administered 1 month apart, was well-tolerated, with an acceptable safety profile, and was immunogenic in virally suppressed, ART-treated people living with HIV aged 16-35 years,” the authors wrote.

SOURCE:

The study was led by Alemnew F. Dagnew, MD, Gates Medical Research Institute, Cambridge, Massachusetts. It was published online on July 1, 2025, in The Lancet HIV.

LIMITATIONS:

The trial population was restricted to people living with HIV who achieved viral suppression through ART, potentially limiting the generalizability of the results to those not on ART, not adhering to treatment, or newly diagnosed with HIV. Additionally, most participants were women, which may have affected overall trial outcomes given the higher risk for tuberculosis among men.

DISCLOSURES:

The study was funded by the Gates Foundation and the Wellcome Trust. Several authors were employees of the Gates Medical Research Institute during the trial. Some authors also received financial aid from other organizations, including Wellcome, UK Research and Innovation, Cancer Research UK, and TB Alliance. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.