Elsevier

Vaccine

Volume 18, Issue 25, 15 June 2000, Pages 2895-2901
Vaccine

Competition among Streptococcus pneumoniae for intranasal colonization in a mouse model

https://doi.org/10.1016/S0264-410X(00)00046-3Get rights and content

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.

Section snippets

Introduction and background

Conjugate vaccines against Streptococcus pneumoniae are currently in clinical trials [1], [2], [3], [4], [5]. These vaccines immunize against 7, 9, of the 90 known pneumococcal serotypes. Preliminary results from these ongoing trials in infants indicate that these vaccines are highly protective against invasive disease [1] and offer significant protection against pneumonia [1] and otitis media [1], [4], from the serotypes included in the vaccine. In addition, the vaccine offers partial

Bacterial strains

S. pneumoniae strains were antibiotic-resistant mutants isolated from strains BG9163 (serotype 6B) and BG8826 (23F) [12]. Optochin-resistant (Opt®) mutants were isolated on tryptic soy agar + 5% sheep’s blood plates (SBA) containing 5 mg/l optochin, and streptomycin-resistant (Str®) mutants were isolated on SBA plates containing 200 mg/l streptomycin. Isolates were restreaked on antibiotic plates and then grown to late log phase and plated on both antibiotic-containing and antibiotic-free

Carriage of a resident strain could inhibit colonization by a challenge strain

Fig. 2 shows the results of 7-day [Fig. 2(a)] and 14-day [Fig. 2(b)] experiments in which BG9163Str® was the resident strain and the otherwise isogenic BG9163Opt® was the challenge strain. Inocula were 7×104 cfu (resident strain) and 4×104 cfu (challenge strain) for the 7-day experiment, and 6×104 cfu (resident strain) and 4×104 cfu (challenge strain) for the 14-day experiment. Competition was observed both in the 7 and 14-day experiment. In the 7-day experiment, carriage of the resident strain

Discussion

The experiments reported here demonstrate that S. pneumoniae carried intranasally can interfere with nasal colonization by a second strain of S. pneumoniae to which the animal is exposed. The removal of this interference by reductions in carriage of vaccine-type S. pneumoniae provides a biological mechanism that could lead to serotype replacement following the introduction of a conjugate pneumococcal vaccine into a population.

As described in Section 1, mathematical models predict that the

Acknowledgements

The authors thank R. Malley for valuable discussions and helpful comments on a draft of the manuscript.

References (18)

  • S.K. Obaro et al.

    Carriage of pneumococci after pneumococcal vaccination

    Lancet

    (1996)
  • H.-Y. Wu et al.

    Establishment of a Streptococcus pneumoniae nasopharyngeal colonization model in adult mice

    Microb. Path.

    (1997)
  • S. Black et al.

    Efficacy of heptavalent conjugate pneumococcal vaccine (Wyeth Lederle) in 37,000 infants and children: impact on pneumonia, otitis media, and an update on invasive disease — Results of the Northern California Kaiser Permanente Efficacy Trial

  • R. Dagan et al.

    Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine

    J. Infect. Dis.

    (1996)
  • J. Eskola et al.

    Clinical evaluation of new pneumococcal vaccines: the Finnish approach

    Devl. Biol. Stand.

    (1998)
  • J. Eskola et al.

    Efficacy of a heptavalent pneumococcal conjugate vaccine (PncCRM) against serotype-specific, culture-confirmed pneumococcal acute otitis media (AOM) in infants and children

  • N. Mbelle et al.

    Immunogenicity and impact on nasopharyngeal carriage of a nonavalent pneumococcal conjugate vaccine

    J. Infect. Dis.

    (1999)
  • R. Dagan et al.

    Effect of a 9-valent pneumococcal vaccine conjugated to CRM197 (PncCRM9) on nasopharyngeal (NP) carriage of vaccine type and non-vaccine type S. pneumoniae (Pnc) strains among day-care-center (DCC) attendees

  • M. Lipsitch

    Bacterial vaccines and serotype replacement: lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae

    Emerg. Infect. Dis.

    (1999)
There are more references available in the full text version of this article.

Cited by (0)

View full text