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Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model
M Lipsitch1, J K Dykes, S E Johnson
1Division of Bacterial and Mycotic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. mlipsitc@hsph.harvard.edu [corrected]
Abstract:
Widespread use of conjugate vaccines against Streptococcus pneumoniae, by reducing carriage of S. pneumoniae serotypes included in the vaccine, may result in an increase in nasopharyngeal carriage of - and disease from - nonvaccine serotypes of the same species. Mathematical models predict that the extent of such replacement will depend positively on the degree to which carriage of vaccine-type S. pneumoniae inhibits acquisition of nonvaccine-type pneumococci, and may depend negatively on the inhibition of vaccine-type pneumococci by nonvaccine-type pneumococci. We used a mouse model of intranasal carriage of pneumococci to test whether such inhibition occurs between different pneumococcal strains. Mice carrying a streptomycin-resistant derivative of S. pneumoniae BG9163 (serotype 6B) as a resident strain showed reduced levels of colonization when challenged intranasally by optochin-resistant derivatives of the same strain and of a serotype 23F pneumococcus, BG8826. Inhibition could be overcome by increasing the dose of the challenge strain. Carriage of optochin-resistant BG9163 did not inhibit acquisition of the streptomycin-resistant variant. Colonization by a challenge strain did not significantly affect the level of colonization with the resident strain. These results provide evidence that is consistent with several hitherto untested assumptions of mathematical models of serotype replacement and suggest that a biological mechanism exists that could account for serotype replacement that is observed in clinical trials. The findings provide a basis for further studies of in vivo interactions between strains of S. pneumoniae.
Insights
Pneumococcal conjugate vaccines may increase non-vaccine serotype carriage. Mouse models show vaccine-type Streptococcus pneumoniae can inhibit non-vaccine type acquisition, supporting serotype replacement theories.
Area of Science:
- Microbiology
- Immunology
- Epidemiology
Background:
- Pneumococcal conjugate vaccines reduce carriage of targeted Streptococcus pneumoniae serotypes.
- Serotype replacement, an increase in non-vaccine serotypes, is a potential consequence of widespread vaccination.
- Mathematical models suggest inter-serotype inhibition influences the extent of serotype replacement.
Purpose of the Study:
- To investigate if carriage of one Streptococcus pneumoniae serotype inhibits the acquisition of other serotypes in a mouse model.
- To provide empirical evidence for assumptions used in mathematical models of pneumococcal serotype replacement.
Main Methods:
- A mouse model of intranasal Streptococcus pneumoniae carriage was employed.
- Mice were colonized with a resident strain (serotype 6B) and challenged with different serotypes.
- Inhibition of colonization was assessed by comparing bacterial loads after challenge.
Main Results:
- Carriage of a vaccine-type (6B) Streptococcus pneumoniae strain reduced colonization by challenge strains (same and 23F serotypes).
- This inhibition effect could be overcome by increasing the challenge dose.
- Conversely, carriage of a non-vaccine type strain (23F) did not inhibit acquisition of the vaccine-type strain.
Conclusions:
- The study provides evidence for biological mechanisms underlying pneumococcal serotype replacement.
- Findings support the hypothesis that competition between Streptococcus pneumoniae serotypes contributes to vaccine-induced shifts in carriage.
- These results validate key assumptions in mathematical models predicting serotype replacement dynamics.