Prophylactic and post-exposure efficacy of a Pichinde virus vector-based tuberculosis vaccine

Area of Science:

• Immunology
• Vaccinology
• Microbiology

Background:

• Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global health threat despite existing vaccines and treatments.
• There is a critical need for new TB vaccines effective in adults, for standalone use, as BCG boosters, or as therapeutic interventions.

Purpose of the Study:

• To develop and evaluate TBpV1, a novel multivalent TB vaccine candidate utilizing a recombinant Pichinde virus (rPICV) vector.
• To assess TBpV1's immunogenicity and protective efficacy against Mtb infection in a mouse model, including standalone, BCG-boosted, and post-exposure settings.

Main Methods:

• Development of TBpV1, a multivalent vaccine comprising three rP18tri-vectored components delivering 13 Mtb antigens.
• Evaluation of antigen-specific CD4+ and CD8+ T cell responses in mice.
• Assessment of TBpV1's efficacy via aerosol challenge with Mtb Erdman, comparing standalone, BCG-boosted, and post-exposure administration.

Main Results:

• The pooled TBpV1 vaccine induced robust antigen-specific CD4+ and CD8+ T cell responses, including polyfunctional Th1 and IL-17-producing cells.
• As a standalone vaccine, TBpV1 significantly reduced Mtb bacterial burden, offering protection comparable to BCG.
• TBpV1 enhanced BCG-induced protection and reduced splenic bacterial burden in a post-exposure setting.

Conclusions:

• Pooling multi-stage antigens via the rP18tri vector maintains immunogenicity and improves protective efficacy.
• TBpV1 is a promising vaccine candidate for both TB prevention and therapeutic intervention, warranting further preclinical evaluation.