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.
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.


BACKGROUND
ClinicalTrials.gov NCT01028326.
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya ; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Laura L
LL
Hammitt
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya.
John
J
Ojal
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya.
Mahfudh
M
Bashraheil
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya ; Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom.
Susan C
SC
Morpeth
KEMRI-Wellcome Trust Research Programme, Centre for Geographic Medicine-Coast, Kilifi, Kenya.
Angela
A
Karani
GlaxoSmithKline Vaccines, Wavre, Belgium.
Ahsan
A
Habib
GlaxoSmithKline Vaccines, Wavre, Belgium.
Dorota
D
Borys
Institute of Child Health, University College London, London, United Kingdom.
David
D
Goldblatt
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.
J Anthony G
JA
Scott
D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D002353:Carrier State; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D006192:Haemophilus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D006193:Haemophilus influenzae / Q000276:immunology; D022362:Hepatitis A Vaccines / Q000008:administration & dosage; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007072:Immunoglobulin D / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D007630:Kenya; D008074:Lipoproteins / Q000276:immunology; D008297:Male; D011008:Pneumococcal Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D013296:Streptococcus pneumoniae / Q000276:immunology; D018074:Vaccines, Conjugate
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D022362:Hepatitis A Vaccines; D007072:Immunoglobulin D; D008074:Lipoproteins; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; C067989:glpQ protein, Haemophilus influenzae