1157. A Novel, Live Streptococcus pneumoniae Vaccine Prevents Acute Otitis Media in Mice
Session: Poster Abstract Session: Innate and Adaptive Immunity to Infections
Saturday, October 22, 2011
Room: Poster Hall B1
Background: 

Acute otitis media (AOM) is the leading reason for physician visits and antibiotic prescriptions in the United States. Streptococcus pneumoniae remains the most common cause of AOM despite the use of conjugate vaccines. We used a novel model of AOM in mice to study the efficacy of a live, attenuated pneumococcal vaccine.

Methods: 

We generated a live, attenuated vaccine strain through deletion of the signal receptor FtsY from the type 19F (ST425) S. pneumoniae strain BHN97. BALB/c mice were vaccinated then boosted twice (3 weeks apart) by IN infection with this strain, or by IP injection of either 13-valent pneumococcal conjugate vaccine (PCV13) or 23-valent pneumococcal polysaccharide vaccine (PPV23), then challenged 1 week later with WT BHN97 or heterologous type 7F (ST191) strain BHN54, both of which had been engineered to express luciferase. Live mice were monitored by bioluminescent imaging every 12 hours for development of AOM or sinusitis. Humoral and cellular immune responses were assessed in normal mice and mice depleted of CD4+ T-cells.

Results: 

The FtsYΔ vaccine was significantly more effective (p < 0.05) than all other vaccines, with only 4 of 25 mice (16%) developing AOM, compared to 40% of PCV13 mice, 60% of PPV23 mice, and 80% of controls. The FtsYΔ vaccine also achieved significant protection against sinusitis (4% of mice developed sinusitis compared to 80-92% for other groups) and heterologous infection (8% of vaccinated mice developed AOM vs. 50% of controls). This superior protection correlated with robust production of IgA, IgG2a, and IgG2b serum antibodies. Production of these antibodies after FtsYΔ infection and vaccine efficacy of the FtsYΔ and PCV13 vaccines were CD4+ T-cell dependent.

Conclusion: 

Protection from AOM and sinusitis in a live pneumococcal vaccine model is dependent on T-cell help for antibody class switching. A novel, live, attenuated FtsY deletion mutant is a promising candidate for further development as a pneumococcal vaccine.


Subject Category: E. Innate and adaptive immunity to infections, including vaccine immunology

Jason Rosch, PhD, Amy Iverson, Jessica Humann, Beth Mann, Geli Gao, Elaine Tuomanen and Jonathan A. McCullers, MD, St. Jude Children's Research Hospital, Memphis, TN

Disclosures:

J. Rosch, None

A. Iverson, None

J. Humann, None

B. Mann, None

G. Gao, None

E. Tuomanen, None

J. A. McCullers, AVIBioPharma: Consultant, Consulting fee
GlaxoSmithKline: Consultant, Consulting fee
Novartis: Consultant, Consulting fee
Pfizer: Consultant, Consulting fee

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.