Is the Interplay Between Maternal Tdap and Pneumococcal Conjugate Vaccines Relevant to Infant Pneumococcal Carriage?

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To The Editor—Maternal pertussis vaccination has been implemented for more than a decade in numerous countries and has demonstrated substantial benefits in preventing pertussis among young infants. In the absence of a monovalent pertussis vaccine, this strategy necessarily relies on combination vaccines that include diphtheria and tetanus toxoids in addition to the pertussis component. Early after implementation, maternal vaccination was shown to be associated with a transient reduction in the immunogenicity of infant vaccines sharing homologous antigens, a phenomenon commonly referred to as the “blunting effect” and related to levels of passively transferred maternal antibodies [1]. Multiple studies have confirmed reduced response to CRM197-conjugated pneumococcal conjugate vaccines (PCVs), deriving from the fact that CRM197 is a diphtheria toxoid mutant [2]. Importantly, no clinical impact of this reduced immunogenicity has been demonstrated, in terms of either pertussis and invasive pneumococcal diseases or nasopharyngeal carriage. A superficial reading of the article by Van den Bosch et al might suggest a clinically relevant negative consequence of maternal Tdap vaccination on pneumococcal carriage [3]. A careful examination of the data, however, does not support such an interpretation. Reanalysis of the data, pooling 2019 to 2021 as a transition period, yielded informative results (Table 1). Most differences between the Tdap and non-Tdap groups was confined to the period of high (94.6%) PCV10 coverage (serotype 6C, 15.2% vs 8.7% [P = .01], respectively; PCV13 serotypes, 32.1% vs 21.7% [P = .003]). In contrast, when PCV13 was widely used (2021–2022), differences were minimal and nonsignificant. Therefore, increasing the use of PCV13 corresponded to smaller differences between the Tdap and non-Tdap groups for PCV13 serotypes and serotype 6C. Most important, independent of maternal Tdap status, the introduction and use of PCV13 were associated with an approximately 3-fold reduction in the carriage of PCV13 serotypes (Tdap group, 32.1% vs 26.6% vs 10.9% [trend test, P < .0001]; non-Tdap group, 21.7% vs 24.0% vs 10.5% [trend test, P < .001]) [4]. These findings directly challenge the validity of the pooled analysis presented and raise serious concerns regarding the appropriateness of combining periods characterized by different PCVs. Furthermore, the reduced response in offspring of Tdap recipients is expected only with CRM197-conjugated PCVs. However, as we show, the main difference in carriage was during the almost exclusively PCV10 period. In PCV10, most vaccine serotypes are not conjugated to any diphtheria-associated antigen (except serotype 19F, for which no problem was shown in the current report); thus, no plausibility for interference with maternal Tdap can be argued.

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