Pneumococcal Diversity: Considerations for New Vaccine Strategies with Emphasis on Pneumococcal Surface Protein A (PspA)

Abstract

SUMMARY Streptococcus pneumoniae is a problematic infectious agent, whose seriousness to human health has been underscored by the recent rise in the frequency of isolation of multidrug-resistant strains. Pneumococcal pneumonia in the elderly is common and often fatal. Young children in the developing world are at significant risk for fatal pneumococcal respiratory disease, while in the developed world otitis media in children results in substantial economic costs. Immunocompromised patients are extremely susceptible to pneumococcal infection. With 90 different capsular types thus far described, the diversity of pneumococci contributes to the challenges of preventing and treating S. pneumoniae infections. The current capsular polysaccharide vaccine is not recommended for use in children younger than 2 years and is not fully effective in the elderly. Therefore, innovative vaccine strategies to protect against this agent are needed. Given the immunogenic nature of S. pneumoniae proteins, these molecules are being investigated as potential vaccine candidates. Pneumococcal surface protein A (PspA) has been evaluated for its ability to elicit protection against S. pneumoniae infection in mouse models of systemic and local disease. This review focuses on immune system responsiveness to PspA and the ability of PspA to elicit cross-protection against heterologous strains. These parameters will be critical to the design of broadly protective pneumococcal vaccines.

The microbiologic and immunologic basis for recurrent otitis media in children

“…Antigens of Immunologic Importance among Middle Ear Pathogens (Table 4) As described previously, there are more than 90 types of S. pneumoniae based on the capsular polysaccharide antigens [5]. Antibody to the capsule is highly speci®c with very little cross reactivity.…”

“…Antibody to PspA appears to be protective [5,26]. Antibody to PspA from dierent strains displays cross-reactivity [5,26].…”

“…A second antigen, pneumococcal surface protein A (PspA) is found on all clinically important strains of S. pneumoniae [17]. Antibody to PspA appears to be protective [5,26]. Antibody to PspA from dierent strains displays cross-reactivity [5,26].…”

Clinical bacteriology and immunology in acute otitis media in children

“…Isolates with 80% relatedness on the dendrogram are considered to be strongly genetically related protein may be able to provide protection against multiple diverse strains of S. pneumoniae. 35 Immune responses to PspA in the sera of various age groups in the general population and in the nasopharynx of 30 children monitored from birth until 1 year of age were evaluated 29 (Fig. 6).…”

Protection against systemic fatal pneumococcal infection by maternal intranasal immunization with pneumococcal surface protein A (PspA)

“…[19][20][21][22][23] Thus, PspA is an attractive candidate for future protein-based pneumococcal vaccines.…”