Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination

Abstract

Trial designIn an earlier trial, Papua New Guinean (PNG) children at high risk of pneumococcal disease were randomized to receive 0 or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7), followed by a single dose of 23-valent pneumococcal polysaccharide vaccine (PPV23) at 9 months of age. We here studied in a non-randomized follow-up trial the persistence of pneumococcal immunity in these children at 3–5 years of age (n = 132), and in 121 community controls of a similar age with no prior pneumococcal vaccination.MethodsCirculating IgG antibody titers to all PCV7 and PPV23-only serotypes 2, 5 and 7F were measured before and after challenge with 1/5th of a normal PPV23 dose. Serotype-specific memory B-cells were enumerated at 10 months and 3–5 years of age for a subgroup of study children.ResultsSerotype-specific IgG antibody titers before and after challenge were similar for children who received PCV7/PPV23, PPV23 only, or no pneumococcal vaccines. Before challenge, at least 89% and 59% of children in all groups had serotype-specific titers ≥ 0.35μg/ml and ≥ 1.0 μg/ml, respectively. Post-challenge antibody titers were higher or similar to pre-challenge titers for most children independent of pneumococcal vaccination history. The rise in antibody titers was significantly lower when pre-challenge titers were higher. Overall the relative number of serotype-specific memory B-cells remained the same or increased between 10 months and 3–5 years of age, and there were no differences in serotype-specific memory B-cell numbers at 3–5 years of age between the three groups.ConclusionsImmunity induced by PCV7 and/or PPV23 immunization in infancy does not exceed that of naturally acquired immunity in 3-5-year-old children living in a highly endemic area. Also, there was no evidence that PPV23 immunization in the first year of life following PCV7 priming induces longer-term hypo-responsiveness.Trial registrationClinicaltrials.gov NCT01414504 and NCT00219401.

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea

“…In the 7vPCV trial PPV was found to be immunogenic when given at age 9 months to PNG infants previously primed with 3 doses of PCV [ 5 ], and antibody titres to PCV and non-PCV serotypes rose in response to a 1/5 th PPV challenge dose at age 3–4 years. These data further contribute to the evidence that long-lasting deleterious effects of PPV immunization in infancy are unlikely [ 43 ]. Limitations of the 7vPCV trial were the relatively long time interval between receipt of PPV at 9 months and assessment of response to challenge at 3–4 years of age, and that the study did not include a group of children who had received PCV with no PPV.…”

Pneumococcal conjugate vaccine primes mucosal immune responses to pneumococcal polysaccharide vaccine booster in Papua New Guinean children

“…Until new PCVs including more serotypes than the current 10- and 13-valent vaccines or serotype-independent vaccines become available, 23vPPV booster vaccination could provide these high-risk children with broader protection than induced by current PCVs alone. We have previously shown that PPV induces serotype-specific systemic IgG responses in PNG infants vaccinated with PCV as well as non-PCV recipients, with no evidence of inducing hypo-responsiveness [3] , [39] , [40] . We here show that a PPV booster results in enhanced mucosal IgA and IgG responses in PCV-primed PNG infants, which importantly could protect children against serotype-specific acquisition and carriage.…”

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

“…Earlier studies in PNG, conducted before PCVs became available, had already shown that despite the limited immunogenicity of PPV in children under 2 years of age, PNG children aged 6 months to 5 years had reduced mortality and severe morbidity due to acute lower respiratory infections (ALRI) if they had been vaccinated with PPV [9,10]. Responding to the concerns raised by the Fiji study, we followed up infants vaccinated as part of the PNG PCV7/PPV trial and found that at age 3–5 years all children responded to a pneumococcal challenge with increased antibody responses [11]. While this suggests that there was no evidence of hyporesponsiveness in the PPV vaccinated PNG children, the study had two limitations.…”