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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Compound 48/80 acts as a potent mucosal adjuvant for vaccination against Streptococcus pneumoniae infection in young
Lingbin Zeng1, Yusi Liu2, Hong Wang2
1College of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing 400016, China; Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, Chengdu 610091, China.
Abstract:
Streptococcus pneumoniae, a major respiratory pathogen, is a leading cause of death among children worldwide. Mucosal vaccination is a recommended method to prevent respiratory infection. However, development of mucosal vaccination is usually hindered due to the lack of safe and effective mucosal adjuvants. Mast cell activator compound 48/80 (C48/80) has been used as a mucosal adjuvant in immunization of adult mice, but its adjuvanticity is not clear in the immunization of young mice. In this study, the adjuvanticity of C48/80 was evaluated when intranasally co-administrated with a pneumococcal vaccine candidate strain SPY1 in a young mice model in comparison with a classical mucosal adjuvant cholera toxin (CT) and a relatively safe mucosal adjuvant Pam2CSK4. All three adjuvants enhanced antibody responses, whereas serum IgG titers were maintained at a stable level during the 3 months after the last immunization only in the SPY1+C48/80 and SPY1+CT groups. Furthermore, both the SPY1+CT group and the SPY1+C48/80 group induced strong Th17 immune response. Notably, C48/80 showed the exceptional ability to promote the clearance of nasal pneumococcal colonization which CT and Pam2CSK4 did not show. We found that C48/80's ability to induce protection against nasal pneumococcal colonization depended on B cells and IL-17A. Additionally, C48/80, as a mucosal adjuvant, showed a greater ability to protect young mice against lethal pneumococcal infection than CT. In comparison with CT, C48/80 also showed a favorable safety. These results reveal a promising perspective for using C48/80 as a mucosal adjuvant to improve protection against pneumococcal diseases early in life.
Insights
Mast cell activator compound 48/80 (C48/80) shows promise as a mucosal adjuvant for young mice against Streptococcus pneumoniae. It enhances antibody and Th17 responses, clears nasal colonization, and offers better protection and safety than cholera toxin.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Streptococcus pneumoniae causes significant childhood mortality, necessitating effective vaccines.
- Mucosal vaccination is ideal for respiratory pathogens but lacks safe, effective adjuvants.
- Mast cell activator compound 48/80 (C48/80) is a potential mucosal adjuvant, but its efficacy in young mice is unproven.
Purpose of the Study:
- To evaluate the adjuvanticity of C48/80 when co-administered intranasally with a pneumococcal vaccine candidate (SPY1) in young mice.
- To compare C48/80's performance against established mucosal adjuvants, cholera toxin (CT) and Pam2CSK4.
- To assess C48/80's safety and protective capabilities against pneumococcal infection and colonization.
Main Methods:
- Intranasal co-administration of SPY1 with C48/80, CT, or Pam2CSK4 in a young mouse model.
- Monitoring of antibody responses (serum IgG titers) over three months.
- Assessment of Th17 immune response induction.
- Evaluation of nasal pneumococcal colonization clearance.
- Testing protection against lethal pneumococcal infection and comparative safety analysis.
Main Results:
- All adjuvants enhanced antibody responses, but only SPY1+C48/80 and SPY1+CT maintained stable IgG titers for three months.
- Both SPY1+CT and SPY1+C48/80 groups induced robust Th17 immune responses.
- C48/80 uniquely promoted clearance of nasal pneumococcal colonization, unlike CT and Pam2CSK4.
- C48/80-induced protection against colonization required B cells and IL-17A.
- C48/80 provided superior protection against lethal pneumococcal infection in young mice compared to CT, with better safety.
Conclusions:
- C48/80 demonstrates significant potential as a mucosal adjuvant for enhancing pneumococcal vaccine efficacy in young mice.
- Its ability to induce strong Th17 responses, clear nasal colonization, and provide robust protection with favorable safety is highly promising.
- C48/80 offers a promising strategy for improving early-life protection against pneumococcal diseases through mucosal vaccination.
