Safety and Immunogenicity of Pneumococcal Conjugate Vaccines in a High-risk Population: A Randomized Controlled Trial of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccine in Papua New Guinean Infants

Abstract

Background: There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population.

Methods: PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age.

Results: One month after the third dose of PCV10 or PCV13, ˃80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85-96) of children vaccinated with PCV10 and 81% (95% CI 72-88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events.

Conclusions: Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed.

Clinical trials registration: NCT01619462.

Keywords: S. pneumonia; Papua New Guinea; antibodies; carriage; pneumococcal conjugate vaccine.

Figure 1.

Flowchart. HIV, human immunodeficiency virus; LTFU, lost to follow-up; Mig, Migration; PCV10, 10-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PV, protocol violation; WC, withdrawn consent.

Figure 2.

GMCs of serotype-specific IgG antibodies. GMCs and 95% CIs for IgG antibodies against shared PCV10/13 serotypes, (*) PCV13-only serotypes, and (**) non-PCV serotype 2 measured before vaccination, at 4 months of age, and at 9 months of age were compared between children vaccinated with either three doses of PCV10 (orange square) or PCV13 (blue circle) using a 2-sample t-test and indicated with (#) when significantly different (P < .05). Abbreviations: CI, confidence interval; GMC, geometric mean concentration; IgG, immunoglobulin G; PCV, pneumococcal conjugate vaccine.

Figure 3.

GM fold change in PCV-induced IgG responses between 4 and 9 months of age. GM fold changes and 95% CIs in vaccine-induced IgG antibody titers between 4 and 9 months of age were calculated for shared PCV10/13 serotypes for both PCV10- (orange square) and PCV13- (blue circle) vaccinated children, as well as for PCV13-only serotypes (*) for the PCV13-vaccinated group. GMs and 95% CIs < 1 correspond to a significant (P < .05) decline in antibody responses. GM fold changes were compared between the groups for each shared vaccine serotype using a 2-sample t-test and when a significant difference was found P-values were included. Abbreviations: CI, confidence interval; GM, geometric mean; IgG, immunoglobulin G; PCV, pneumococcal conjugate vaccine.