Hammitt L.L., Ojal J., Bashraheil M., Morpeth S.C., Karani A., Habib A., Borys D., Goldblatt D., Scott J.A.G.
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; GlaxoSmithKline Vaccines, Wavre, Belgium; Institute of Child Health, University College London, London, United Kingdom; Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
Hammitt, L.L., KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States; Ojal, J., KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya; Bashraheil, M., KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya; Morpeth, S.C., KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Karani, A., KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya; Habib, A., GlaxoSmithKline Vaccines, Wavre, Belgium; Borys, D., GlaxoSmithKline Vaccines, Wavre, Belgium; Goldblatt, D., Institute of Child Health, University College London, London, United Kingdom; Scott, J.A.G., KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom, Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
Background: The 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. Methods: 600 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. Results: Following 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. Conclusions: Vaccination 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 Registration: ClinicalTrials.gov. NCT01028326 © 2014 Hammitt et al.
diphtheria pertussis tetanus vaccine; Haemophilus influenzae protein D conjugate vaccine; Haemophilus influenzae vaccine; hepatitis A vaccine; immunoglobulin G; unclassified drug; antibody production; article; bacterial colonization; bacterial load; child; controlled study; double blind procedure; drowsiness; drug hypersensitivity; drug tolerance; enzyme linked immunosorbent assay; female; fever; human; immune response; immunogenicity; injection site erythema; injection site pain; injection site swelling; Kenya; male; nasopharynx; nose smear; opsonization; opsonophagocytic killing assay; phase 3 clinical trial; pneumococcal infection; randomized controlled trial; serotype; Streptococcus pneumoniae; throat culture; vaccination; Antibodies, Bacterial; Bacterial Proteins; Carrier Proteins; Carrier State; Child, Preschool; Diphtheria-Tetanus-Pertussis Vaccine; Double-Blind Method; Female; Haemophilus Infections; Haemophilus influenzae; Haemophilus Vaccines; Hepatitis A Vaccines; Humans; Immunization Schedule; Immunization, Secondary; Immunoglobulin D; Infant; Infant, Newborn; Kenya; Lipoproteins; Male; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate