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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Evaluation of cross-protection between S. Pneumoniae serotypes 35B and 29 in a mouse model
Ellie Kim1, Jian He2, Robin M Kaufhold1
1Department of (1)Infectious Disease/Vaccines Discovery, United States.
Abstract:
Pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease but in turn have also resulted in replacement with non-vaccine serotypes. One such serotype, 35B, a multidrug resistant type, has been associated with an increase in disease. Mice were immunized intramuscularly with monovalent pneumococcal polysaccharide 35B conjugated to CRM197 containing aluminum phosphate adjuvant on days 0, 14, and 28. Pneumococcal enzyme-linked immunosorbent assay, opsonophagocytic killing assays, and competition OPA were performed for STs 35B and 29 to measure serotype-specific binding and functional antibodies. On day 52, mice were intratracheally challenged with S. pneumoniae ST29 to evaluate cross-protection. 35B-CRM197 immunized mice had binding and functional antibodies to both PnPs 35B and 29. 35B-CRM197 immunized mice were 100% protected from IT challenge with S. pneumoniae ST29 as compared to 30% survival in the naïve group. Future vaccines containing polysaccharide 35B, such as the investigational 21-valent PCV, V116, may provide cross protection against the non-vaccine serotype 29 due to structural similarity.
Insights
Pneumococcal conjugate vaccines (PCVs) reduce disease but can lead to replacement by other serotypes. A new vaccine targeting 35B shows promise for cross-protection against non-vaccine serotypes like 29.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Pneumococcal conjugate vaccines (PCVs) have decreased vaccine-type pneumococcal disease.
- Replacement by non-vaccine serotypes, such as multidrug-resistant 35B, is an emerging concern.
- Serotype 35B is increasingly associated with pneumococcal disease.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of a monovalent pneumococcal polysaccharide 35B conjugate vaccine (35B-CRM197).
- To assess the potential for cross-protection against non-vaccine serotype 29.
Main Methods:
- Mice were immunized with 35B-CRM197 conjugate vaccine with aluminum phosphate adjuvant.
- Serotype-specific antibody responses were measured using ELISA and opsonophagocytic killing assays (OPA).
- Mice were challenged with Streptococcus pneumoniae serotype 29 to assess protection.
Main Results:
- 35B-CRM197 immunization induced functional antibodies against both serotype 35B and 29.
- Immunized mice showed 100% survival after challenge with serotype 29.
- Naïve control mice had only 30% survival after challenge.
Conclusions:
- The 35B-CRM197 vaccine is immunogenic and provides complete protection against serotype 29 challenge in a mouse model.
- Future vaccines containing polysaccharide 35B may offer cross-protection against serotype 29 due to structural similarities.
- This highlights the potential of targeting serotype 35B to combat replacement disease.
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