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Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Mucosal and systemic immunization with a novel attenuated pneumococcal vaccine candidate confer serotype independent
Kaifeng Wu1, Run Yao2, Hong Wang1
1Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University, Chongqing 400016, PR China.
Insights
A novel live attenuated vaccine strain, SPY1, demonstrated significant protection against Streptococcus pneumoniae infection in mice. Mucosal vaccination with SPY1 provided superior efficacy compared to existing vaccines, highlighting its potential for preventing pneumococcal disease.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Streptococcus pneumoniae remains a leading cause of infectious disease and mortality in young children globally.
- Current vaccines have limitations, necessitating the development of novel preventative strategies.
Purpose of the Study:
- To evaluate the protective efficacy of a novel live attenuated vaccine strain, SPY1, against Streptococcus pneumoniae infection in murine models.
- To compare the efficacy of mucosal versus systemic immunization with SPY1.
Main Methods:
- The SPY1 strain was characterized by defects in capsule, teichoic acids, and pneumolysin.
- Lactate dehydrogenase assays and in vivo animal experiments were conducted.
- Murine models were used for colonization, invasive infection, and passive protection studies.
Main Results:
- SPY1 exhibited significantly attenuated virulence and reduced nasopharyngeal colonization.
- Mucosal immunization with SPY1 provided superior protection against colonization and invasive disease compared to systemic immunization and commercial vaccines.
- SPY1 induced serotype-independent antibodies and a mixed cellular immune response, with serum conferring passive protection.
Conclusions:
- The live attenuated SPY1 strain shows promising protective efficacy against pneumococcal infection.
- Mucosal vaccination with SPY1 offers a potentially superior strategy for preventing pneumococcal disease, including invasive infections.
Abstract:
Despite the availability of effective vaccines, Streptococcus pneumoniae is still one of the major infectious diseases causing substantial morbidity and mortality in children under 5 years old. In this study, we demonstrate the protective efficacy of S. pneumoniae SPY1, a novel live attenuated vaccine strain against pneumococcal infection in murine models. This strain was characterized by defects in three important pneumococcal virulence factors including capsule, teichoic acids and pneumolysin. The lactate dehydrogenase assays and in vivo animal experiments demonstrated a significantly attenuated virulence and a reduced nasopharyngeal colonization for the SPY1 strain. We also show that mucosal and systemic immunization with the live SPY1 strain induced protective immune responses against pneumococci. Mucosal immunization with SPY1 offered better protection against colonization challenge with strains TIGR4 and serotype 19F than systemic SPY1 immunization. In invasive infection models, mucosal vaccination with the SPY1 strain conferred complete protection against D39 and clinical serotype 6B and 3 strains. Notably, intranasal vaccination with the SPY1 strain conferred superior protection against pneumococcal invasive disease compared with the commercial available vaccines. SPY1 strain was shown to elicit high levels of serotype-independent antibodies and a mixed cellular immune response. Besides, the SPY1 serum was able to passively protect mice against invasive challenge with D39 strain, indicating the protective effect of the antibody-mediated responses. Together, the SPY1 strain may be a promising live vaccine strain to protect pneumococcal infection.

