The candidate tuberculosis vaccine Mtb72F/AS02 in PPD positive adults: a randomized controlled phase I/II study

Area of Science:

• Immunology
• Vaccinology
• Infectious Disease Epidemiology

Background:

• Tuberculosis (TB) prevention via vaccination could significantly decrease the global TB burden.
• The Mtb72F/AS02 vaccine candidate demonstrated immunogenicity and good tolerability in PPD-negative individuals.
• This study assesses Mtb72F/AS02 in Mycobacterium-primed populations, including BCG-vaccinated and previously infected adults.

Purpose of the Study:

• To evaluate the safety and immunogenicity of the Mtb72F/AS02 vaccine in Mycobacterium-primed adults.
• To compare reactogenicity and immune responses between Mtb72F/AS02 and AS02 vaccine adjuvants.
• To assess the persistence of vaccine-induced immune responses for six months post-vaccination.

Main Methods:

• An observer-blind controlled trial involving 38 participants (20 BCG-vaccinated, 18 Mtb-infected).
• Participants received three doses of Mtb72F/AS02 or AS02 adjuvant alone at one-month intervals (3:1 randomization).
• Safety (adverse events) and immunogenicity (T-cell responses, antibody levels, cytokines) were monitored for six months.

Main Results:

• Mtb72F/AS02 was well-tolerated in BCG-vaccinated adults and showed increased reactogenicity in Mtb-infected adults; all adverse events were self-limiting.
• No serious adverse events were reported, and adverse events were not clearly linked to vaccine-induced immune responses.
• The vaccine induced persistent polyfunctional Mtb72F-specific CD4(+) T-cell responses and anti-Mtb72F humoral immunity, with detectable IFN-γ post-vaccination.

Conclusions:

• Mtb72F/AS02 is a safe and immunogenic TB vaccine candidate in Mycobacterium-primed adults.
• The vaccine elicits durable cellular and humoral immune responses crucial for TB prevention.
• Further clinical evaluation of Mtb72F/AS02 is recommended based on these findings.