Croney, C.M., Coats, M.T., Nahm, M.H., Briles, D.E. & Crain, M.J. PspA family distribution, unlike capsular serotype, remains unaltered following introduction of the heptavalent pneumococcal conjugate vaccine. Clin. Vaccine Immunol. 19, 891-896

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.47). 04/2012; 19(6):891-6. DOI: 10.1128/CVI.05671-11
Source: PubMed


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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Nasopharyngeal (NP) carriage and invasive pneumococcal disease (IPD) attributable to serotypes in the 7-valent pneumococcal conjugate vaccine (PCV7) declined dramatically after vaccine introduction, whereas non-PCV7 serotypes increased modestly. Characteristics of pneumococcal carriage and IPD among children in Atlanta, GA, were compared during 2 time periods: before PCV7 introduction and before 13-valent PCV (PCV13) introduction. Methods: NP swabs from 231 and 451 children 6-59 months old receiving outpatient medical care were obtained in 1995 and 2009, respectively. A total of 202 and 47 IPD cases were identified in children younger than 5 years of age in 1995 and in 2008 to 2009, respectively, through active, population-based surveillance in Atlanta. Isolates were serotyped, sequence-typed (ST) and tested for antimicrobial susceptibility. Results: Forty percent (93/231) of children in 1995 and 31% (139/451) in 2009 were colonized with Streptococcus pneumoniae; 60% and 0.7% were PCV7 serotypes, respectively. In 1995, PCV7 serotypes accounted for 83% and 19A accounted for 5% of IPD compared with no PCV7 serotypes and 19A accounting for 49% of IPD in 2009 (P < 0.001). In 2009, PCV13 serotypes accounted for 22% of carriage (mostly 19A) and 60% of invasive isolates (P < 0.001). ST320 accounted for 66% and 52% of 19A carriage and IPD isolates in 2009, respectively; all ST320 isolates were multidrug-resistant. No ST320 NP or IPD isolates were identified before PCV7. Conclusions: Serotype distribution among NP and IPD isolates in Atlanta has shifted to non-PCV7 serotypes; 19A was the leading serotype for both. The multidrug-resistant ST320 strain was responsible for two-thirds of 19A carriage isolates and half of IPD isolates. The predominance of serotype 19A in carriage and IPD among children in Atlanta highlights the potential direct and indirect benefits anticipated by implementation of PCV13 in the community.
    No preview · Article · Oct 2012 · The Pediatric Infectious Disease Journal
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the presence of normal serum, complement component C3 is deposited on pneumococci primarily via the classical pathway. Pneumococcal surface protein A (PspA), a major virulence factor of pneumococci, effectively inhibits C3 deposition. PspA's C terminus has a choline-binding domain that anchors PspA to the phosphocholine (PC) moieties on the pneumococcal surface. C-reactive protein (CRP), another important host defense molecule, also binds to PC, and CRP binding to pneumococci enhances complement C3 deposition through the classical pathway. Using flow cytometry of PspA(+) and PspA(-) strains, we observed that the absence of PspA led to exposure of PC, enhanced the surface binding of CRP, and increased the deposition of C3. Moreover, when the PspA(-) mutant was incubated with a pneumococcal eluate containing native PspA, there was decreased deposition of CRP and C3 on the pneumococcal surface compared with incubation with an eluate from a PspA(-) strain. This inhibition was not observed when a recombinant PspA fragment, which lacks the choline-binding region of PspA, was added to the PspA(-) mutant. Also, there was much greater C3 deposition onto the PspA(-) pneumococcus when exposed to normal mouse serum from wild-type mice as compared with that from CRP knockout mice. Furthermore, when CRP knockout mouse serum was replenished with CRP, there was a dose-dependent increase in C3 deposition. The combined data reveal a novel mechanism of complement inhibition by a bacterial protein: inhibition of CRP surface binding and, thus, diminution of CRP-mediated complement deposition.
    No preview · Article · Oct 2012 · The Journal of Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The standard opsonization phagocytosis and killing assay (OPKA) for antibodies to pneumococcal capsular polysaccharide was modified to permit evaluation of protection-mediating antibodies to pneumococcal surface protein A (PspA). We found that by increasing the incubation time with complement and phagocytes from 45 min to 75 minutes that the protective activity could be readily detected. In another modification we used a capsule type 2 target strain that expressed PspA but not pneumococcal surface protein C (PspC). Using these modifications separately or in combination, rabbit antisera to recombinant α-helical or proline-rich domains of PspA mediated > 50% killing of the target strain. The ability of normal human sera to mediate killing of pneumococci in this modified OPKA correlated with their levels of antibody to PspA and their ability to protect mice against fatal infection with a type 3 strain. Passive protection of mice against pneumococci and killing in the modified OPKA were both lost when normal human serum was adsorbed with rPspA on Sepharose, thus supporting the potential utility of the modified OPKA to detect protective antibody to PspA. In the standard OPKA, monoclonal antibody to PspA was strongly protective in the presence of sub-protective amounts of anti-capsule. Thus, the currently established high-throughput OPKA for antibody to capsule could be modified in either of two ways to permit evaluation of opsonic efficacy of antibodies to PspA.
    Full-text · Article · Aug 2013 · Clinical and vaccine Immunology: CVI
Show more