Reduced-dose schedules with pneumococcal conjugate vaccine: impact on nasopharyngeal carriage and herd immunity

Abstract

The success of the 4-dose schedule with 7-valent pneumococcal conjugate vaccine (PCV7) is based on direct protection against vaccine serotype pneumococcal disease in vaccinees but also on the observed large herd effect in unvaccinated age groups. However, the nasopharyngeal vacant niche is filled by non-vaccine serotype pneumococci. A reduced-dose vaccination schedule would lower the needle-burden for infants and save costs. Adequate immune responses after a reduced-dose schedule implicating adequate direct protection in vaccinees have been demonstrated but the impact on carriage and herd immunity are unknown. We showed that a reduced-dose PCV7-schedule with 3 (at age 2, 4 and 11 months) or even 2 doses (at 2 and 4 months) adequately reduced vaccine serotype pneumococcal carriage in vaccinated children and parents. This implicates that herd effects will be preserved after implementation of a reduced-dose schedule. However, a reduced-dose schedule did not prevent nasopharyngeal replacement in both children and parents. We showed that PCV7 facilitated nasopharyngeal acquisition of non-vaccine serotypes, in particular of serotype 19A. Also, a temporary increase in nasopharyngeal colonization with S. aureus was observed. Furthermore, we showed that vaccine serotype pneumococci have been virtually eliminated in the population 3 years after implementation of PCV7 in the Dutch National Immunization Program (NIP). The findings in this thesis support implementation of a 2+1- or even 2-dose PCV schedule in the NIP. Current PCVs prevent pneumococcal disease and save lives but broader coverage vaccines, which include serotype 19A, are needed for further pneumococcal disease prevention in the near future. Furthermore, due to the adaptive nature of the pneumococcus, surveillance of disease, immune responses and carriage remains warranted.