Invasive and noninvasive Streptococcus pneumoniae capsule and surface protein diversity following the use of a conjugate vaccine

Abstract

The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media. While many studies have reported its potential efficacy for IPD, not much is known about the epidemiology of noninvasive disease following its introduction. We characterized the capsular types and surface protein genes of noninvasive pediatric pneumococcal isolates collected between 2002 and 2010 (n = 1,058) at Children's of Alabama following the introduction of PCV7 and tested a subset of noninvasive and previously characterized IPD isolates for the presence of the pspA, pspC, and rrgC genes, which encode protection-eliciting proteins. PCV7 serotypes had dramatically decreased by 2010 (P < 0.0001), and only 50% of all noninvasive infections were caused by the PCV13 capsular serotypes. Serotype 19A accounted for 32% of the noninvasive isolates, followed by serotypes 35B (9%), 19F (7%), and 6C (6%). After 7 years of PCV7 usage, there were no changes in the frequencies of the pspA or pspC genes; 96% of the strains were positive for family 1 or 2 pspA genes, and 81% were also positive for pspC. Unexpectedly, more noninvasive than invasive strains were positive for rrgC (P < 0.0001), and the proportion of rrgC-positive strains in 2008 to 2010 was greater than that in 2002 to 2008 (IPD, P < 0.02; noninvasive, P < 0.001). Serotypes 19F, 19A, and 35B were more frequently rrgC positive (P < 0.005) than other serotypes. A vaccine containing antigens, such as PspA, PspC, and/or RrgC, can provide coverage against most non-PCV13-type pneumococci. Continued surveillance is critical for optimal future vaccine development.

Fig 1

Serotype distribution of noninvasive isolates by period of isolation. Serotype distributions for IPD isolates are shown for the years 2002 through 2010. Each seasonal period spans from July 1 through June 30 of the second year. N, total number of isolates from the indicated period; PCV7, capsular serotypes in the heptavalent pneumococcal conjugate vaccine; PCV13, capsular serotypes in the 13-valent PCV that are not included in PCV7; NVT, typeable serotypes not included in the PCV13; NT, nontypeable isolates. Overall, 49% of noninvasive infections were caused by serotypes included in the Prevnar13 (PCV13).

Fig 2

Gene frequencies in IPD and noninvasive isolates. IPD (n = 157) and noninvasive (n = 221) isolates were typed by PCR for pspA, pspC, or rrgC. Gene names separated by slashes refer to pneumococci that are positive for those genes. All strains were typed at least twice for each gene. ***, P < 0.0001. P values were obtained using Fisher's exact test.

Fig 3

Gene frequencies over a period of time in IPD and noninvasive isolates. IPD (n = 157) and noninvasive (n = 221) isolates were typed by PCR for pspA, pspC, or rrgC and grouped into two periods, 2002 to 2008 and 2008 to 2010. *, P < 0.05; **, P < 0.001. P values were obtained using Fisher's exact test.

Fig 4

Strains of PCV13 serotypes are more likely to be rrgC positive. All strains were grouped together by serotype, regardless of disease group, and rrgC frequency was determined. Only serotypes with 4 isolates or more are shown; however, all strains were included in determining the proportion expressing rrgC in the PCV7, PCV13, and NVT groups, even if a serotype is not represented in the graph. The number of isolates per serotype is given in parentheses. *, P < 0.005, per Fisher's exact test with Bonferroni's correction.