Immunogenicity and Immune Memory after a Pneumococcal Polysaccharide Vaccine Booster in a High-Risk Population Primed with 10-Valent or 13-Valent Pneumococcal Conjugate Vaccine: A Randomized Controlled Trial in Papua New Guinean Children

Anita Van Den Biggelaar,Peter Richmond,Peter Jacoby,Lea-Ann Kirkham,William Pomat,Rebecca Ford,Jacinta Francis,Geraldine Masiria,Birunu Nivio,Deborah Lehmann,Megan Passey,Sandra Wana

doi:10.3390/vaccines7010017

Abstract

We investigated the immunogenicity, seroprotection rates and persistence of immune memory in young children at high risk of pneumococcal disease in Papua New Guinea (PNG). Children were primed with 10-valent (PCV10) or 13-valent pneumococcal conjugate vaccines (PCV13) at 1, 2 and 3 months of age and randomized at 9 months to receive PPV (PCV10/PPV-vaccinated, n = 51; PCV13/PPV-vaccinated, n = 52) or no PPV (PCV10/PPV-naive, n = 57; PCV13/PPV-naive, n = 48). All children received a micro-dose of PPV at 23 months of age to study the capacity to respond to a pneumococcal challenge. PPV vaccination resulted in significantly increased IgG responses (1.4 to 10.5-fold change) at 10 months of age for all PPV-serotypes tested. Both PPV-vaccinated and PPV-naive children responded to the 23-month challenge and post-challenge seroprotection rates (IgG ≥ 0.35 μg/mL) were similar in the two groups (80–100% for 12 of 14 tested vaccine serotypes). These findings show that PPV is immunogenic in 9-month-old children at high risk of pneumococcal infections and does not affect the capacity to produce protective immune responses. Priming with currently available PCVs followed by a PPV booster in later infancy could offer improved protection to young children at high risk of severe pneumococcal infections caused by a broad range of serotypes.

Highlights

Streptococcus pneumoniae remains a leading cause of death in children under5 years of age and is estimated to cause over 500,000 deaths and nearly 14 million episodes of the disease annually, mainly in young children in low-income countries [1]
We have recently shown in a head-to-head study that the two currently available pneumococcal conjugate vaccines (PCV), the 10-valent (PCV10) and 13-valent (PCV13) vaccines, are comparably safe and immunogenic in Papua New Guinea (PNG) infants when given at 1, 2 and 3 months of age in line with national guidelines [5]
In the pneumococcal polysaccharide vaccine (PPV)-naive group IgG responses remained the same or declined between 9 and 10 months of age at the same rate for PCV10- and PCV13 serotypes varied between 44% (PCV13)-primed children. These findings demonstrate that PPV is immunogenic in 9-month-old infants who have been primed with PCV10 or PCV13

Summary

Introduction

5 years of age and is estimated to cause over 500,000 deaths and nearly 14 million episodes of the disease annually, mainly in young children in low-income countries [1]. The epidemiology of pneumococcal infections is different in high-risk compared to low-risk settings, including that the onset and burden of pneumococcal colonization and disease happen at a younger age, often within weeks after birth, and that the spectrum of colonizing and invading pneumococcal serotypes is broader [1,2,3,4]. Preventing pneumococcal disease in children in high-risk settings requires strategies that are tailored towards providing the earliest possible protection against the broadest possible spectrum of invasive pneumococcal serotypes, and that are highly effective for at least the first 12–18 months of life when the burden of disease and death from S. pneumoniae is highest. An alternative is to complement priming with 3 doses of PCV with one dose of the 23-valent pneumococcal polysaccharide vaccine (PPV); this approach may elevate the waning antibody titers but may induce protection against a broader spectrum of serotypes during the most critical period of life

Methods

Results

Conclusion