hRSV is the main cause of infections in the lower respiratory tract, causing pneumonia, bronchiolitis and alveolitis in children younger than two years old. The infection is associated with the development of recurrent obstructive episodes in children with genetic predisposition. These hRSV infections also cause a high number of hospitalizations during the winter season.
At Pontificia Universidad Católica de Chile, a vaccine has been developed to prevent hRSV infection, which is the conventional Bacillus Calmette Guerin (BCG) vaccine modified to recombinantly express the Nucleoprotein of hRSV (rBCG-N-hRSV). This vaccine has proven to be safe and immunogenic in different animal models, both in Chile and the USA. Doses of this vaccine have been manufactured under Current Good Manufacturing Practices (cGMP) conditions in USA, which are suitable to be tested in humans. Due to the unique immunogenic and safety characteristics observed in animal models used to test the efficacy of the rBCG-N-hRSV vaccine prototype, this clinical study will evaluate safety, tolerability and immunogenicity of the immunogenic cGMP formulation in healthy adults.
Main objective: To characterize the safety and tolerability of escalating doses of the rBCG-N-hRSV vaccine, including doses of 5x10\^3, 5x10\^4 and 1x10\^5 CFU (1%, 10% and 100% of the total dose) in healthy adult males of 18 to 50 years of age.
Secondary objectives:
1. To characterize the immune response against the Nucleoprotein of the hRSV in the previously stated escalating doses in the rBCG-N-hRSV.
2. To characterize the immune response against the Mycobacterium in the previously stated escalating doses in the rBCG-N-hRSV.
Study design: It corresponds to a phase I study, double blind (participant and personnel of the study) for the immunization of the tested vaccine or the control vaccine (Conventional BCG) within each cohort, to be performed in healthy adult males of 18 to 50 years of age.
After a full clinical and laboratory evaluation to discard diseases, immunodeficiencies and latent tuberculosis infection, the participants will be enrolled into three cohorts in a open and successive manner. Within each cohort, they will be randomly and in a blind-manner assigned to receive the tested vaccine (rBCG-N-hRSV) or the control vaccine (conventional BCG).
Cohort A: 6 participants vaccinated with 5x10\^3 CFU of the rBCG-N-hRSV (1/100 part of the full dose) and 2 participants vaccinated with the conventional BCG (full dose).
Cohort B: 6 participants vaccinated with 5x10\^4 CFU of the rBCG-N-hRSV (1/10 part of the full dose) and 2 participants vaccinated with the conventional BCG (full dose).
Cohort C: 6 participants vaccinated with 1x10\^5 CFU of the rBCG-N-hRSV (full dose) and 2 participants vaccinated with the conventional BCG (full dose).
Each cohort will be completed within two weeks, followed by a period of 4 weeks of follow-up, in which the security data will be evaluated by a Data and Safety Monitoring Board (DSMB), who will determinate whether, according to the previously defined parameters, the escalation to the next cohort is possible, the cohort must be repeated, or whether the study must be stopped.
The DSMB is constituted by 5 physician experts in microbiology, virology/vaccinology and tuberculosis, with a wide national recognition, affiliated to institutions different from the sponsoring institution.
Number of participants: A minimum of 24 subjects, 8 by cohort. 18 participants will receive the tested vaccine and 6 will receive the control vaccine.
Main variables: Safety and tolerability.
* Evaluation of reactogenicity (Local and systemic Adverse Events-AE)
* Evaluation of laboratory AE
* Serious AE
* Evaluation of the presence of the vaccine in body fluids
Secondary variables: Immunogenicity
* Evaluation of the immune response against M. bovis BCG.
* Evaluation of the immune response against hRSV-N.
