Streptococcus pneumoniae is a bacterial pathogen implicated in many respiratory and systemic infections, including pneumonia, meningitis, otitis media, bacteremia, sinusitis, peritonitis, and arthritis. Infection with S. pneumoniae can be fatal; other serious results of infection can include neurological effects (e.g., learning disabilities, seen in meningitis patients) or hearing loss (in recurrent otitis media infections). Young children and the elderly are at a particularly high risk for infection with S. pneumoniae, as are immuno-compromised populations and members of certain ethnic groups.
Historically, antimicrobial therapies have been useful in reducing morbidity and mortality rates associated with invasive pneumococcal disease; however, the increasing prevalence of multi-drug resistant strains of S. pneumoniae poses troubling difficulties for attempts to control infections through drug therapy alone.
Vaccination efforts have recently proven effective in reduction of incidence of S. pneumoniae infection rates. Current vaccines contain polysaccharide molecules from the capsule of different serotypes of S. pneumoniae; more than 90 different serotypes have been identified, with different incidences worldwide. Some vaccines, known as “unconjugated” vaccines, contain free polysaccharides. More recently, “conjugated” vaccines, in which saccharide molecules are linked to a peptide carrier, have been developed. An unconjugated vaccine containing polysaccharides from 23 different pneumococcal serotypes has been licensed for use in children over 2 years of age; a conjugate vaccine containing 7 different polysaccharide valencies has been licensed for pediatric use. Introduction and use of this 7-valent conjugate vaccine, PREVNAR® (produced by Wyeth Pharmaceuticals, Inc. of Philadelphia, Pa. and containing polysaccharides from serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F conjugated to the Diphtheria CRM197 protein), in the United States has reduced the incidence of invasive pneumococcal disease (IPD) in children nearly 94% (from 80 per 100,000 in 1998-1999 to 4.6 per 100,000 in 2003).
While young children are among those most at risk for S. pneumoniae infections, disproportionate morbidity and mortality result from invasive pneumococcal disease occurring in older adults. The incidence of invasive pneumococcal infection begins to increase at about age 50 years and increases sharply at age 65 years. S. pneumoniae is the most common cause of community-acquired pneumonia in the United States, resulting in hospitalizations and deaths in persons over 65 years (Robinson, K. A. et al., JAMA 285: 1729-35, 2001). Deaths occur in approximately 14% of patients hospitalized with invasive disease. Persons living in long term care facilities remain a particularly susceptible population for invasive pneumococcal disease as compared to similar older persons living in community settings (Kupronia, B. A., et al., JAGS 51: 1520-1525, 2003).
The only currently licensed pneumococcal vaccine for use in adult populations is the 23 valent unconjugated polysaccharide vaccine. Although this vaccine has been recommended by the CDC Advisory Committee on Immunization Practices (ACIP) Guidelines for prevention of pneumococcal disease in persons 65 years of age or older, significant controversy exists relating to its efficacy. Specifically, wide variation in clinical efficacy has been observed in with this vaccine, which may be related, for example, to age, or disease manifestation (see, e.g., Fedson et al., Arch. Intern. Med., 154: 2531-2535, 1994; and French J. Infect., 46: 78-86, 2003). The vaccine appears to be particularly ineffective in protecting the elderly against pneumococcal pneumonia, and also in protecting any population against otitis media infections. Additionally, meta-analyses of randomized controlled studies have not found a clear protective effect for pneumococcal pneumonia in high-risk groups such as elderly populations (See, e.g., Fine, M. J., et al., Arch. Int. Med. 154: 2666-2677, 1994; Moore, R. A., BMC Fam. Prac. 1: 1-10, 2000; Conaty, S., et al., Vaccine 22: 3214-3224, 2004; and Jackson, L. A., et al., N. Engl. J. Med. 348: 1747-1755, 2003. Furthermore, analyses of immuno-protective effects and duration of response have suggested populations such as the older populations and immuno-compromised patients may generate only limited immune response following polysaccharide vaccination, and resulting antibody concentrations may decrease rapidly subsequent to vaccination (See, e.g., Davidson, M., et al., Arch. Intern Med. 154: 2209-2214, 1994; Rodriguez-Barradas M. C., J. Infect. Dis. 173: 1347-1353, 1996; Rubins, J. B., J. Infect. Dis. 178: 431-440, 1998; and Sankilampi, U., J. Infect. Dis. 176: 1100-1104, 1997. Moreover, once a subject has been initially vaccinated with the unconjugated polysaccharide vaccine, revaccination has been found to result in subsequent hyporesponsiveness. (See, e.g., Artz et al., Clin. Microbiol. Rev. 16: 308-318, 2003; Mufson, M. A., et al., Vaccine 9: 403-407, 1991; Borgondo, J. M., et al., Proc. Soc. Exp. Biol. Med. 157: 148-154, 1978; and Linnemann, G. C., et al., Arch Intern. Med. 146: 1554-1556, 1996.
There remains a need for improved strategies for protecting high risk populations, and particularly older and elderly populations, from infections with S. pneumoniae. 
USPTO Backgrounds
USPTO Backgrounds