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Immunogenicity and Safety of an Investigational Combined Haemophilus influenzae Type B-Neisseria meningitidis Serogroups C and Y-Tetanus Toxoid Conjugate Vaccine

Nolan, Terry MB BS, PhD*; Richmond, Peter MB BS†‡§; Marshall, Helen MB BS, MPH¶∥; McVernon, Jodie MB BS, PhD*; Alexander, Karyn MB ChB, MPH*; Mesaros, Narcisa MD**; Aris, Emmanuel PhD**†; Miller, Jacqueline MD**‡‡; Poolman, Jan PhD§§; Boutriau, Dominique MD§§

Pediatric Infectious Disease Journal: March 2011 - Volume 30 - Issue 3 - pp 190-196
doi: 10.1097/INF.0b013e3181fcb2bf
Original Studies

Background: Neisseria meningitidis serogroups B, C, and Y cause most meningococcal disease in industrialized countries. A Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was evaluated.

Methods: A total of 1104 infants (randomized 3:1:1) were vaccinated at 2, 4, and 6 months with HibMenCY-TT, MenC-CRM197 + Hib-TT, or Hib-TT. At 12 to 15 months, HibMenCY-TT and MenC-CRM-primed children received HibMenCY-TT; Hib-TT-primed received N. meningitidis serogroup B Hib-outer membrane protein complex. Antibody concentrations and rabbit/human complement serum bactericidal antibody titers (rSBA/hSBA) were determined. Safety was monitored after each dose (diary cards for first 31 days) until 6 months postdose 4.

Results: Postdose 3, rates of antipolyribosylribitol phosphate ≥1 μg/mL and rSBA-MenC ≥1:128 in HibMenCY-TT recipients were noninferior to licensed controls. Percentages reaching 0.15 μg/mL (1.0 μg/mL postdose 3) and antipolyribosylribitol phosphate GMC were significantly higher after HibMenCY-TT than Hib-TT postdose 2 and postdose 3. The GMC remained significantly higher before and after dose 4. Proportions of HibMenCY-TT recipients with rSBA ≥1:8 were 95.6% (MenC), 98.6% (MenY) postdose-2, ≥99% for MenC/Y postdose 3 and 4; hSBA ≥1:4 were 95.5% (MenC), 89.8% (MenY) postdose 2, >97% for MenC/Y postdose 3 and 4. HibMenCY-TT had a similar safety profile to control vaccines.

Conclusions: HibMenCY-TT induced noninferior Hib and MenC responses compared with monovalent Hib and MenC conjugates with a comparable safety profile. Bactericidal antibodies against MenC/Y were induced after 2 doses of HibMenCY-TT.

From the *Vaccine and Immunisation Research Group, Murdoch Children's Research Institute and School of Population Health, University of Melbourne, Victoria, Australia; †School of Paediatrics and Child Health, University of Western Australia, Subiaco, Western Australia, Australia; ‡Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia; §Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia; ¶School of Paediatrics and Reproductive Health, University of Adelaide, South Australia, Australia; ∥Vaccinology and Immunology Research Trials Unit, Department of Paediatrics, Women's and Children's Hospital, South Australia, Australia; **Group of Companies, Wavre, Belgium; ‡‡GlaxoSmithKline Group of Companies, King of Prussia, PA; §§GlaxoSmithKline Group of Companies, Rixensart, Belgium.

Accepted for publication August 19, 2010.

Supported by GlaxoSmithKline Biologicals. Funding included all costs associated with the development and the publishing of the present manuscript.

Presented in part at the 45th Annual Meeting of the Infectious Diseases Society of America; October 4–7, 2007; San Diego, CA, and at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12–15, 2009; San Francisco, CA.

E.A., D.B., N.M., J.P., and J.M. are employees of GlaxoSmithKline Biologicals (GSK). J.P., J.M., and D.B. own stock options. J.P. and D.B. are designated inventor on a variety of patents owned by GSK. H.M., T.N., P.R., J.McV., and K.A. are investigators in studies funded by GSK, but receive no personal remuneration from GSK for their contributions.

T.N., H.M., P.R., and J.McV. received travel support to attend scientific meetings to present independent scientific data and chair workshops. T.N. has received an honorarium for membership of an independent DSMB for an unrelated vaccine. H.M. and J.M.V. have been members of a vaccine advisory board. P.R. has received Institutional funding from GSK for investigator-led epidemiologic studies.

GlaxoSmithKline Biologicals was involved in all stages of the study conduct and analysis. The corresponding author had full access to the data and was responsible for submission of the publication. All authors contributed to the study and were involved in writing and reviewing the manuscript.

This trial has been registered at www.clinicaltrials.gov NCT00134719.

Address for correspondence: Terry Nolan, MBBS, PhD, Melbourne School of Population Health, University of Melbourne, L5/207 Bouverie St, Carlton 3010, Australia. E-mail: t.nolan@unimelb.edu.au.

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© 2011 Lippincott Williams & Wilkins, Inc.