PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

Abstract

<jats:title>ABSTRACT</jats:title><jats:p>Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD.</jats:p>

Invasive and Noninvasive Streptococcus pneumoniae Capsule and Surface Protein Diversity following the Use of a Conjugate Vaccine

“…A total of 1,130 noninvasive strains were collected; 72 strains were excluded because they were duplicates of the same capsular type from the same patient, similar to another isolate from the same clinical episode, not viable, or the patient was Ͼ18 years old. The analyses included 1,058 noninvasive isolates and 157 IPD isolates characterized previously (6).…”

“…The introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) has led to sufficient protection against colonization to almost completely eliminate invasive disease caused by the seven PCV capsular types (4, 6B, 9V, 14, 18C, 19F, and 23F), which caused the majority of invasive pneumococcal diseases (IPDs) prior to 2000. However, only a few years after the introduction of PCV7, serotype replacement (an increase in the incidence of IPD caused by non-PCV7 capsular types) was observed (6)(7)(8)(9)(10). In 2010, a new 13-valent vaccine was introduced in the United States to provide protection against the original PCV7 serotypes plus 6 additional capsular serotypes (1, 3, 5, 6A, 7F, and 19A) known to cause IPD.…”

“…PCV13 has also been licensed for use against otitis media (11). Previous reports have shown that PCV13 protects against approximately 60 to 70% of all pneumococci globally postintroduction of the PCV7 (6,(12)(13)(14), and nonvaccine serotypes have been reported to cause serious diseases, such as meningitis (6,8). The occurrence of serotype replacement only a few years following the introduction of PCV7 and the fact that there are Ͼ90 known capsular serotypes (15) raise concerns about the long-term usage of capsule-based vaccines.…”

“…The surface virulence proteins of pneumococci, in particular, are important nonpolysaccharide vaccine candidates. Pneumococcal surface protein A (PspA) is a protein on virtually all pneumococci (6,20) and is important for the inhibition of the classical complement pathway, working specifically by competing with binding by C-reactive protein to block complement deposition (21). PspA elicits antibody-mediated protection against invasive infection through its alpha-helical regions.…”

“…We also determined the gene frequencies of the pneumococcal protein-based vaccine candidates pspA, pspC, and rrgC (pilus type 1) in a subset of noninvasive isolates (this study) and previously characterized IPD isolates (6).…”