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Persistence of Immunity Following a Booster Dose of Haemophilus Influenzae Type B-Meningococcal Serogroup C Glycoconjugate Vaccine: Follow-up of a Randomized Controlled Trial

Khatami, Ameneh MB ChB*; Snape, Matthew D. MD*; John, Tessa MA*; Westcar, Sharon BSc*; Klinger, Chaam MB BS*; Rollinson, Llinos BSc*; Boutriau, Dominique MD; Mesaros, Narcisa MD; Wysocki, Jacek PhD‡§; Galaj, Andrzej PhD; Yu, Ly-Mee MSc; Pollard, Andrew J. PhD*

The Pediatric Infectious Disease Journal: March 2011 - Volume 30 - Issue 3 - p 197-202
doi: 10.1097/INF.0b013e3181f728fd
Original Studies

Background: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) wane after early infant immunization.

Methods: Children previously immunized in a randomized controlled trial at ages 2, 3, and 4 months with DTPa-IPV-Hib and MenC-CRM197 (MenC-CRM group) or DTPa-IPV and Hib-MenC-TT (Hib-MenC-TT group) had blood samples drawn at 1 and 2 years following a booster dose of Hib-MenC-TT at 12 to 15 months of age. A blood sample was also drawn at the year 2 follow-up from a separately recruited age-matched control group who had not received a booster.

Results: In 271 children at year 1, mean 14.6 months (range: 12–18 months) following the Hib-MenC-TT booster, MenC bactericidal titers above the protective threshold (rSBA ≥1:8) was demonstrated in 89.0% of the Hib-MenC-TT group and 69.5% of MenC-CRM participants. Antipolyribosylribitol phosphate Ig ≥1.0 μg/mL (Hib correlate for long-term protection) was seen in 94.9% and 82.5%, respectively.

In 379 participants (including 72 control children) at year 2 (age: 39–43 months, 25–31 months post Hib-MenC-TT) persistence of MenC antibodies was demonstrated in 67.1% of the Hib-MenC-TT group and 40.5% of the MenC-CRM group, compared with 44.1% of control group participants. Antipolyribosylribitol phosphate Ig ≥1.0 μg/mL was seen in 89.0%, 74.7%, and 38.9%, respectively.

Conclusions: A toddler Hib-MenC-TT booster helps sustain immunity against Hib to 3½ years of age. Persistence of MenC antibody is similar in children primed with MenC-CRM197 in infancy who receive a booster Hib-MenC-TT, to those who receive no booster. Persistence of MenC antibody is better when primed and boosted with Hib-MenC-TT.


From the *Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; †GSK Biologicals, Rixensart, Belgium; ‡Specjalistyczny Zespol Opieki nad Matka i Dzeckiem, Poznan, Poland; §Poznań University of Medical Sciences, Poznan, Poland; ¶VITAMED, Bydgoszcz, Poland; and ∥Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom.

Accepted for publication August 12, 2010.

Supported by GlaxoSmithKline Biologicals, Rixensart, Belgium. With the exception of the authors employed by GSK Biologicals (D.B. and N.M.), no authors have received direct payment from GSK Biologicals. The sponsor funded the study and developed the study protocol in collaboration with A.J.P. and M.D.S. Employees of the sponsor reviewed the manuscript before submission for publication. Also supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the NIHR Biomedical Research Centre Programme, which also provides support to the Oxford Vaccine Group (to M.D.S. and T.J.), received financial assistance from GSK Biologicals to attend conferences (to A.K., M.D.S., J.W., and A.G.), and received honoraria for giving lectures (to J.W.).

Andrew J. Pollard acts as chief and principal investigator for clinical trials conducted on behalf of Oxford University, sponsored by vaccine manufacturers (Novartis Vaccines, GlaxoSmithKline, Sanofi-Aventis, Sanofi-Pasteur MSD, and Pfizer Vaccines), and has received assistance from vaccine manufacturers to attend scientific meetings. Industry sourced honorariums for lecturing or writing are paid directly to an independent charity or an educational/administrative fund held by the Department of Paediatrics, University of Oxford. Dominique Boutriau and Narcisa Mesaros are employees of GSK Biologicals.

All authors have completed the Unified Competing Interest form available at: (available on request from the corresponding author).

Ethical approval was granted by Oxfordshire Research Ethics Committee B (Reference: 07/Q1605/33) in the UK, and the relevant Ethics committee in Poland. registration number: NCT00454987.

Address for correspondence: Ameneh Khatami, MBChB, Oxford Vaccine Group, Department of Paediatrics, CCVTM, Churchill Hospital, Oxford, OX3 7LJ, United Kingdom. E-mail:

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© 2011 Lippincott Williams & Wilkins, Inc.