Immunity & infection
Jorge Soto, Phd Student
Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile. Multinational FOCIS Centers of Excellence.
The human respiratory syncytial virus (hRSV) is among the leading pathogens that cause acute respiratory tract infections, resulting in bronchiolitis and pneumonia in the children, elderly and immunocompromised populations. Efforts for the licensing of a vaccine both protective and cost/effective against this virus, have been unsuccessful up to date. Our laboratory developed a recombinant Mycobacterium bovis BCG that expresses the Nucleoprotein of hRSV (rBCG-N) with promising protective capacities. Pre-clinical studies showed that disease parameters -such as weight loss, PMN cells infiltration and viral loads- are reduced in immunized, as compared to non-immunized mice. Immunization was also able to induce a Th1-like immune response, especially suited for the clearance of this virus, with the secretion of IFN-g by CD4+ and activation of cytotoxic CD8+ T cells, with both cell types required for the protection, as transfer of only one of them into naïve mice does not protect upon challenge. Higher antibodies titers against the virus -and several of its proteins- are elicited upon immunization and challenge, as compared to non-immunized mice. Remarkably, these antibodies are capable of protecting challenged naïve mice when sera transfers are performed. This vaccine was manufactured under GMP conditions, exhibiting the same protective capacities seen for the non-GMP vaccine in mice. Recently, a Phase 1 clinical trial was performed with this GMP vaccine, exhibiting significant safety and immunogenicity in healthy adults. These data support the notion that this vaccine is a promising candidate to protect the human population against hRSV.