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A systematic review of invasive pneumococcal disease vaccine failures and breakthrough with higher-valency pneumococcal conjugate vaccines in children

ABSTRACT Introduction The pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV/PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) protect against vaccine-serotype invasive pneumococcal disease (VT IPD). However, VT IPD can still occur in fully or partially vaccinated children (vaccine failure or breakthrough). We performed a systematic review of vaccine failures and breakthrough IPD with PCV10 and PCV13 in ≤5-year-olds. Areas covered We searched Scopus/Medline/EMBASE to retrieve articles/abstracts published between 1/2008-7/2019. We excluded reports only including data from ≥6-year-olds, exclusively assessing PCV7-vaccinated children or children with comorbidities. Twenty-six reports (20 PCV13, 1 PCV10, 5 both), covering studies with various designs in six continents, using different schedules, were included. Collectively, they reported 469 VT IPD cases classified as vaccine failures and 403 as breakthrough. Vaccine failure and breakthrough rates were low: 8.4% and 9.3%, respectively, of all IPD in vaccinated children, consistent with the vaccines’ high effectiveness. The main serotypes associated with vaccine failure/breakthrough were 19A, 3 and 19F for PCV13 and 14, 6B and vaccine-related 19A and 6A for PCV10. Expert opinion As we move to vaccines with more serotypes, it is not only important to consider which serotypes are added, but also monitor and address incomplete protection against specific serotypes. PLAIN LANGUAGE SUMMARY What is the context? Pneumococcal conjugate vaccines have been given to children for over 20 years to prevent infections caused by the bacterium Streptococcus pneumoniae (such as pneumonia, meningitis and sepsis). At least 100 different types of S. pneumoniae, so called serotypes, exist, but a relatively small number causes most disease. Two current vaccines (Synflorix, GSK and Prevnar 13, Pfizer) protect against 10 to 13 serotypes and have significantly reduced pneumococcal disease caused by these serotypes. A rise in serotypes not targeted by these vaccines has lessened the vaccines’ expected impact. As no vaccine is 100% protective, some serotypes targeted by the current vaccines continue to circulate. What is new? We performed a systematic literature review to evaluate which serotypes are most often associated with invasive disease occurring after receives all planned pneumococcal vaccine doses (vaccine failure) or after a child receives part of the planned vaccine doses (breakthrough). We found that vaccine failures and breakthrough disease were uncommon with both vaccines, irrespective of the administered schedule. A small number of serotypes were responsible for most vaccine failures and breakthrough disease with both vaccines. What is the impact? The low rate of vaccine failures and breakthrough disease observed with the current vaccines confirms their high effectiveness in preventing pneumococcal disease. The primary consideration in developing pneumococcal conjugate vaccines that include more than 13 serotypes will be how additional protection they can provide. Reduced protection against individual serotypes remains a risk. The evaluation of current vaccines demonstrates that incomplete protection against specific serotypes should also be addressed.