Immunogenicity, Impact on Carriage and Reactogenicity of 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine in Kenyan Children Aged 1–4 Years: A Randomized Controlled Trial

Abstract

BackgroundThe impact on carriage and optimal schedule for primary vaccination of older children with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) are unknown.Methods600 Kenyan children aged 12–59 months were vaccinated at days 0, 60 and 180 in a double-blind randomized controlled trial according to the following vaccine sequence: Group A: PHiD-CV, PHiD-CV, diphtheria/tetanus/acellular pertussis vaccine (DTaP); Group B: PHiD-CV, DTaP, PHiD-CV; Group C: hepatitis A vaccine (HAV), DTaP, HAV. Nasopharyngeal carriage of Streptococcus pneumoniae was measured at five timepoints. In 375 subjects, serotype-specific responses were measured by 22F-inhibition ELISA and opsonophagocytic killing assays (OPA) one month after vaccination.ResultsFollowing one dose of PHiD-CV, >90% of recipients developed IgG≥0.35 µg/mL to serotypes 1, 4, 5, 7F, 9V and 18C and OPA≥8 to serotypes 4, 7F, 9V, 18C, 23F. After a second dose >90% of recipients had IgG≥0.35 µg/mL to all vaccine serotypes and OPA≥8 to all vaccine serotypes except 1 and 6B. At day 180, carriage of vaccine-type pneumococci was 21% in recipients of two doses of PHiD-CV (Group A) compared to 31% in controls (p = 0.04). Fever after dose 1 was reported by 41% of PHiD-CV recipients compared to 26% of HAV recipients (p<0.001). Other local and systemic adverse experiences were similar between groups.ConclusionsVaccination of children aged 12–59 months with two doses of PHiD-CV two to six months apart was immunogenic, reduced vaccine-type pneumococcal carriage and was well-tolerated. Administration of PHiD-CV would be expected to provide effective protection against vaccine-type disease.Trial RegistrationClinicalTrials.gov NCT01028326

10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers

“…The carriage rate of non-vaccine serotypes remained unchanged at 45·7% (16 of 35). These findings are consistent with the patterns observed in the parent study [21]. …”

“…Notably, these kinetics of memory B cells differed from those of plasma antibodies, suggesting independence in the generation of the two compartments. There were significant increases in plasma antibodies against all assessed serotypes after each dose of PHiD-CV, with the highest increases being observed after the first dose [21]. …”

“…This analysis is a substudy of a double-blind, randomized controlled trial that evaluated the immunogenicity, impact on nasopharyngeal carriage and reactogenicity of PHiD-CV among 600 Kenyan children aged 12-59 months [21]. In a randomly selected subset of 35 children aged 12-23 months who received PHiD-CV at enrolment and 6 months later, the frequencies of antigen-specific memory B cells were assessed on the day of enrolment before vaccination and 1 month after each dose of PHiD-CV.…”

Measuring the effects of pneumococcal conjugate vaccine (PCV7) on Streptococcus pneumoniae carriage and antibiotic resistance: The Palestinian-Israeli Collaborative Research (PICR)

“…Interestingly, randomized controlled intervention studies assessing the direct effect of different PCVs on carriage, reported an early decrease of S. pneumoniae carriage among vaccinated individuals [15,16]. Implementation of PCV7 did not affect overall S. pneumoniae carriage prevalence in our population-based study.…”

Pneumococcal Carriage in Children under Five Years in Uganda-Will Present Pneumococcal Conjugate Vaccines Be Appropriate?

“…Importantly, studies from South Africa, Kenya and Gambia show promising effectiveness [15,18–21]. In a study on patients with IPD in Uganda between 2003–2007 the potential vaccine serotype coverage was 55% for PCV7, 58% for PCV10 and 79% for PCV13 [22].…”