Real-World Impact of Pneumococcal Conjugate Vaccines on Vaccine Serotypes and Potential Cross-Reacting Non-Vaccine Serotypes

Abstract

Background: Clinical trials and serological studies have demonstrated that vaccine-induced antibodies can cross-react with some non-vaccine serotypes. However, there are limited longitudinal data on the impact of pneumococcal conjugate vaccines (PCV) on cross-reactive serotypes after implementation in immunization programs. This study examines the impact of PCVs on pneumococcal disease cases due to potential cross-reactive serotypes.

Methods: Eleven countries with serotyped invasive pneumococcal disease (IPD) surveillance data that had introduced PCV10 or PCV13 were identified. The analysis focused on IPD cases due to serotypes included in PCV10 and PCV13 (PCV10/13 VTs: 6B, 9V, 19F, 23F; PCV13 only VTs: 6A, 19A) and to vaccine-related serotypes (VRTs: 6C, 9N, 23A, 23B) that may be immunologically related to VTs in children under 5 years old. For each country, the number of IPD cases were charted over time according to serogroup.

Results: Following PCV introduction, reductions in VT IPD cases were observed in all countries, while some VRT IPD cases remained unchanged or increased. Serotype 19A cases declined in PCV13 countries but increased in countries that introduced PCV10. VRT 6C cases rose in PCV10 countries but showed minimal change in PCV13 countries. In PCV13 countries, 9N cases remained unchanged while 23A and 23B experienced modest increases.

Conclusions: The inclusion of VT 19A in PCV13, but not in PCV10, may account for the significant increase in VRT 19A cases in PCV10 countries. The slight change in VRT 6C cases in PCV13 countries compared to the significant rise in PCV10 countries suggests that PCV13 provides cross-protection for serotype 6C through serotype 6A. Cross-protection could not be determined for other VRTs, as their cases increased or remained unchanged or had insufficient data for evaluation.

Keywords: Streptococcus pneumoniae; invasive pneumococcal disease; pneumococcal conjugate vaccines; serotype epidemiology.

Figure 1

Trends in IPD cases attributable to serogroups 6, 9, 19, and 23 after PCV10 introduction. For Brazil, Chile, Finland, and Paraguay, only PCV10 (medium gray) was introduced during the study period. For Colombia, PCV7 was the first PCV implemented (medium gray), followed by PCV10 (dark gray). Brazil, Chile, Colombia, and Paraguay did not have data available for serogroups 9 and 23.

Figure 1

Trends in IPD cases attributable to serogroups 6, 9, 19, and 23 after PCV10 introduction. For Brazil, Chile, Finland, and Paraguay, only PCV10 (medium gray) was introduced during the study period. For Colombia, PCV7 was the first PCV implemented (medium gray), followed by PCV10 (dark gray). Brazil, Chile, Colombia, and Paraguay did not have data available for serogroups 9 and 23.

Figure 2

Trends in IPD cases attributable to serogroups 6, 9, 19, and 23 after PCV13 introduction. In Germany, both PCV10 and PCV13 are licensed and recommended; however, PCV13 is used primarily with >90% uptake in NIP. For Germany, Israel, Mexico, South Africa, and USA, PCV7 (medium gray) and PCV13 (dark gray) were implemented. In Argentina, only PCV13 (dark gray) was introduced. Argentina and Mexico did not have data for serogroups 9 and 23.