Modulation of immune responses induced by recombinant BCG expressing LTAK63 adjuvant in an immunotherapeutic model vaccine

Author(s)

Navarrete, Josselyn Andrea Yaguana ; Rodriguez, Dunia ; Kanno, Alex Issamu ; Leite, Luciana Cezar de Cerqueira ; Trentini, Monalisa Martins

• Document type: Journal article
• Source: Vaccine; v. 57, p. 7-pg., 2025-05-12.

Abstract

Tuberculosis (TB) remains a major global health issue, with current treatments relying on prolonged multidrug regimens that can reduce patient compliance, and lead to drug resistance. Immunotherapeutic vaccines against Mycobacterium tuberculosis (Mtb) offer a novel approach. We have previously shown that the recombinant BCG expressing LTAK63 adjuvant (rBCG-LTAK63) decreases bacillary load and lung inflammation in Mtb-infected mice. In this work, we further investigated specific immune mechanism induced in mice infected with Mtb and treated with rBCG-LTAK63 in combination with conventional chemotherapy; different routes of administration of rBCG-LTAK63 were evaluated, such as SC, IN, and IV. Immunotherapy with rBCG-LTAK63 induces early innate immune cells migration (predominantly NK cells and monocytes/macrophages) to distinct sites; increased IFN-gamma, TNF-alpha, and IL-17 T cells, FoxP3 expressing regulatory T cells correlating with reduced bacillary load, particularly with IN administration. The findings highlight the potential of rBCG-LTAK63 to complement TB treatment. (AU)

• FAPESP's process: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma
• Grantee: Luciana Cezar de Cerqueira Leite
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/06454-0 - Evaluation of BCG expressing adjuvant LTAK63 in a humanized mouse model as a therapeutic vaccine for Tuberculosis
• Grantee: Monalisa Martins Trentini
• Support Opportunities: Scholarships in Brazil - Post-Doctoral