Persistence of antibody response following a booster dose of Hib-MenC-TT glycoconjugate vaccine to five years: a follow-up study.
BACKGROUND
Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) persist better to 3½ years of age after a 12-month booster dose of a combination Hib-MenC glycoconjugate vaccine (Hib-MenC-TT) in children primed in infancy with Hib-MenC-TT and diphtheria-tetanus-acellular-pertussis-inactivated poliovirus vaccine (DTaP-IPV) than in those who received a monovalent MenC-CRM197 and DTaP-IPV-Hib (also TT conjugated). Pertussis antibodies against filamentous hemagglutinin and pertactin are higher at 5 and 12 months in children who received DTaP-IPV compared with those immunized with DTaP-IPV-Hib. We evaluated whether these differences persisted to later childhood, following a preschool booster of DTaP-IPV at 3½ years of age.


METHODS
Children in the United Kingdom and Poland previously enrolled in the aforementioned randomized-controlled trial had a blood sample taken at 5 years of age. Antipolyribosylribitol phosphate (Hib) IgG and MenC bactericidal antibody (baby rabbit complement) titers were compared between those immunized in infancy (at 2, 3 and 4 months) with DTaP-IPV/Hib-MenC-TT (Hib-MenC-TT group) and those who received DTaP-IPV-Hib with a monovalent MenC-CRM197 (control group). Antibody concentrations against filamentous hemagglutinin, pertactin and pertussis toxin were also measured at this visit.


RESULTS
Two hundred sixty-eight participants aged 58-64 months were enrolled. MenC baby rabbit complement titers ≥1:8 were seen in 115 of 194 of the Hib-MenC-TT group (59.3% [52.0-66.3%]) and 26 of 58 (44.8% [31.7-58.5%]) of control group participants. MenC baby rabbit complement geometric mean titers were 30.4 and 11.3, respectively (ratio 2.70 [1.55- .73]). Antipolyribosylribitol phosphate (Hib) IgG concentrations ≥ 1.0 μg/mL were seen in 171 of 197 (86.8% [81.3-91.2%]) of the Hib-MenC-TT group and 36 of 58 (62.1% [48.4-74.5%]) of control group participants. Antipolyribosylribitol phosphate IgG geometric mean concentrations (GMCs) were 3.82 and 1.67, respectively (ratio 2.29 [1.59-3.28]). Sixty-eight UK participants aged 58-63 months had sera analyzed for the pertussis antigens (44 DTaP-IPV recipients, 14 DTaP-IPV-Hib recipients). Antipertussis toxin IgG GMCs were similar for participants immunized with DTaP-IPV and DTaP-IPV-Hib: 8.2 EL.U/mL (6.1 - 10.9) compared with 7.2 EL.U/mL (3.9 - 13.4). Antifilamentous hemagglutinin IgG GMCs were higher for DTaP-IPV recipients (164.7 EL.U/mL [119.4-227.1]) compared with DTaP-IPV-Hib recipients (66.8 EL.U/mL [43.8-101.7]), as were antipertactin IgG GMCs: 102.8 EL.U/mL (67.1-157.3) compared with 23.4 EL.U/mL (15.1-36.2).


CONCLUSIONS
Vaccines used for infant immunization against Hib and MenC differ in their ability to prime responses to a booster dose of Hib-MenC-TT, and this difference persists to at least 5 years of age. Persistence of antipertussis antibody following a preschool booster of DTaP-IPV is also influenced by immunizations received at 2, 3 and 4 months of age, underlining the importance of infant immune priming in the maintenance of antibody levels through childhood.
Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre and Department of Paediatrics, University of Oxford, Oxford, United Kingdom. ameneh.khatami@paediatrics.ox.ac.uk
Ameneh
A
Khatami
Matthew D
MD
Snape
Jacek
J
Wysocki
Tessa M
TM
John
Sharon
S
Westcar
Narcisa
N
Mesaros
Kavitha
K
Peddiraju
Dominigue
D
Boutriau
Ly-Mee
LM
Yu
Andrew J
AJ
Pollard
D000907:Antibodies, Bacterial / Q000097:blood*; D001770:Blood Bactericidal Activity; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D011044:Poland; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D013997:Time Factors; D006113:United Kingdom; D014611:Vaccination / Q000379:methods*
D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D013745:Tetanus Toxoid; D003165:Complement System Proteins