Protective immunity against Streptococcus pneumoniae infection
1. Project objective - Streptococcus pneumoniae is a bacterial pathogen that causes various diseases such as pneumonia, septicemia, and invasive diseases. After the introduction of pneumococcal conjugate vaccines (PCV), there has been a significant reduction in penicillin-non susceptible and multidrug-resistant invasive pneumococcal diseases (IPD) in different countries. Although these vaccines have reduced the occurrence of diseases, they do not provide protection against all the serotypes (more than 90), accentuating the need for the development of novel prophylactic strategies. The oral commensals, such as Streptococcus mitis, holds promise as a vaccine candidate against S. pneumoniae, due to its genetic, ecological and immune similarities with S. pneumoniae. Therefore, our objective is to explore the role of the oral commensal S. mitis in conferring protective immunity against mouse lung infection with various S. pneumoniae serotypes/strains.
2. Harm - We expect that although the mice undergoing experimentation may show short-term mild to moderate distress or suffering, they will not show any significant impairment of their well-being or general condition. Of note, we have acquired experience conducting these kinds of experiments for four years, as described in our previous FOTS - 8481.
3. Predicted benefit – Our study will generate high quality data that will not only provide invaluable insights into the development of novel prophylactic strategies against pneumococcal infections but also have implications for better understanding the host-commensal-pathogen interactions. Specifically, we expect that this study will generate significant evidence on: i) the humoral and T cell immune responses ensued due to mucosal immunization of mice with S. mitis strains, ii) the protective efficacy of S. mitis expressing the pneumococcal capsules against pneumococcal infections, and iii) the type of protective immune responses against S. pneumoniae, which is elicited by immunization with S. mitis strains.
4. Numbers and types of animals to be used – CD1 female mice (total 480 in number) will be used during the whole duration of this project.
5. How to comply with the 3Rs - It is unavoidable to replace mouse model for this study as it involves complex host-commensal-pathogen interactions. We have focused on reducing the number of animals, but also use sufficient numbers (total 480) to provide reliable findings depending on our previous experience (FOTS – 8481) and prospective power analysis. We expect that the mice undergoing experimentation may show short-term mild to moderate distress or suffering. The human endpoint by euthanasia will be considered when the murine weight loss is more than 10% of their body weight at the beginning of the experiment or any score in any category, as described in the attached score sheet.
2. Harm - We expect that although the mice undergoing experimentation may show short-term mild to moderate distress or suffering, they will not show any significant impairment of their well-being or general condition. Of note, we have acquired experience conducting these kinds of experiments for four years, as described in our previous FOTS - 8481.
3. Predicted benefit – Our study will generate high quality data that will not only provide invaluable insights into the development of novel prophylactic strategies against pneumococcal infections but also have implications for better understanding the host-commensal-pathogen interactions. Specifically, we expect that this study will generate significant evidence on: i) the humoral and T cell immune responses ensued due to mucosal immunization of mice with S. mitis strains, ii) the protective efficacy of S. mitis expressing the pneumococcal capsules against pneumococcal infections, and iii) the type of protective immune responses against S. pneumoniae, which is elicited by immunization with S. mitis strains.
4. Numbers and types of animals to be used – CD1 female mice (total 480 in number) will be used during the whole duration of this project.
5. How to comply with the 3Rs - It is unavoidable to replace mouse model for this study as it involves complex host-commensal-pathogen interactions. We have focused on reducing the number of animals, but also use sufficient numbers (total 480) to provide reliable findings depending on our previous experience (FOTS – 8481) and prospective power analysis. We expect that the mice undergoing experimentation may show short-term mild to moderate distress or suffering. The human endpoint by euthanasia will be considered when the murine weight loss is more than 10% of their body weight at the beginning of the experiment or any score in any category, as described in the attached score sheet.