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

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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.

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