Randomized, Open-Label Study of the Impact of Age on Booster Responses to the 10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine in Children in India

Abstract

In this phase III, open-label, multicenter, and descriptive study in India, children primed with 3 doses (at ages 6, 10, and 14 weeks) of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) were randomized (1:1) to receive a booster dose at 9 to 12 (early booster) or 15 to 18 months old (late booster) in order to evaluate impact of age at booster. We also evaluated a 2-dose catch-up vaccination plus an experimental booster dose in unprimed children age 12 to 18 months. The early booster, late booster, and catch-up vaccinations were administered to 74, 95, and 87 children, respectively; 66, 71, and 81 children, respectively, were included in the immunogenicity according-to-protocol cohort. One month postbooster, for each PHiD-CV serotype, >95.2% (early booster) and >93.8% (late booster) of the children had antibody concentrations of >0.2 g/ml; >96.7% and >93.0%, respectively, had opsonophagocytic activity (OPA) titers of >8. The postbooster antibody geometric mean concentrations (GMCs) were in similar ranges for early and late boosters; the OPA titers appeared to be lower for most PHiD-CV serotypes (except 6B and 19F) after the early booster. After dose 2 and postbooster, for each PHiD-CV serotype, >88.6% and >96.3%, respectively, of the catch-up immunogenicity according-to-protocol cohort had antibody concentrations of >0.2 g/ml; >71.4% and >90.6%, respectively, had OPA titers of >8. At least 1 serious adverse event was reported by 2 children in the early booster (skin infection and gastroenteritis) and 1 child in the catch-up group (febrile convulsion and urinary tract infection); all were resolved, and none were considered by the investigators to be vaccine re- Streptococcus pneumoniae is the leading cause of pneumonia, meningitis, and septicemia. Worldwide, pneumococcal infections are estimated to have been responsible for 541,000 deaths in 2008 in children Ͻ5 years of age, with a high burden in Southeast Asia (108,000 deaths in 2008 in children Ͻ5 years) (http://www.who.int/ immunization/monitoring_surveillance/burden/estimates/Pneumo _hib/en/).The 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) has been shown to be immunogenic and well tolerated in infants in India (1). Moreover, recent double-blind randomized controlled trials demonstrated that infant vaccination with PHiD-CV was effective in preventing vaccine-type invasive pneumococcal disease (2, 3), communityacquired pneumonia (4, 5), and acute otitis media (6).PHiD-CV is typically given as a 2-or 3-dose primary series in infants, with a booster dose administered in their second year of life. However, in some countries, vaccination visits beyond the first year are not routine; thus, vaccination ends at the age of Յ6 months, without a booster dose being administered. Developing countries generally opt for a 3-dose primary schedule for PHiD-CV, without a booster dose. Moreover, compliance with vaccination decreases as children get older (7). Nevertheless, epi...

Impact of Pneumococcal Conjugate Vaccine Administration in Pediatric Older Age Groups in Low and Middle Income Countries: A Systematic Review

“…Characteristics of included studies are listed ( Table 1 ). Eight of the studies were conducted in low income countries [ 17 – 20 , 22 – 25 ], two in lower middle income countries [ 26 – 27 ], six in upper middle income countries [ 15 , 16 , 21 , 28 – 30 ], and two in high income countries [ 31 , 32 ], though they were classified as upper middle income countries at the time of the study. These studies were published between 2008 and 2014, with three presented as abstracts at the ISPPD [ 15 , 23 , 25 ].…”

“…Eight studies report on 1 dose of PCV catch up [ 15 – 21 , 30 ] and eight report on 2 doses of PCV catch up [ 23 – 28 , 31 , 32 ], with two reporting both one and two dose extended age regimens [ 22 , 29 ]. Nine studies were from Africa [ 17 – 20 , 22 – 25 , 27 ] , seven from South America [ 15 , 16 , 21 , 28 , 30 – 32 ], and two from Asia [ 26 , 29 ]. Eight examined PCV 7[ 17 – 21 , 28 – 29 , 31 ], nine examined PCV 10 [ 15 , 16 , 22 – 24 , 26 , 27 , 30 , 32 ], and one examined PCV 13 [ 25 ].…”

Safety profile of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV)

“…Catch-up groups not included in the analyses of pooled safety data were children in study 062 who received a 2+1 catch-up schedule in the second year of life [14], children in study 013 who received one dose above 2 years of age [11], and children in studies 042 and 046, who received two doses above 2 years of age [12,13] (Supplementary Table 4). …”

“…Some groups of children were not included in the analyses of pooled solicited and unsolicited AE data but were assessed separately (Supplementary Table 4): those who received three catch-up doses in the second year of life or catch-up above 24 months of age in studies 013 [11], 042 [12], 046 [13], and 062 [14], and additional dose groups from studies 042 [12] and 046 [13]. Other safety results that were considered separately were those from FinIP study 043, in which safety reporting was based on spontaneous reporting only [5], and those in populations at higher risk for pneumococcal infection: HIV-infected and HIV-exposed uninfected children in study 034 (submitted manuscript).…”

Panel 6: Vaccines

“…43 Studies examined the ability of immunization with PHiD-CV to induce an anamnestic antibody response following boosting, 44 the immunogenicity of booster and catch-up doses of the vaccine, 45 and the effect of variation in age on the immunogenicity of individual booster doses. 46 In each instance, the protein D component of the vaccine demonstrated excellent immunogenicity.…”