Background: The highest rate of invasive meningococcal disease is among children under 2 years of age. There is currently no licensed quadrivalent (serogroups A, C, W-135, and Y) meningococcal glycoconjugate vaccine approved for infants. We evaluated the immunogenicity and reactogenicity of a novel quadrivalent nonadjuvanted meningococcal glycoconjugate vaccine (MenACWY-CRM) in healthy infants.
Methods: One hundred eighty infants (90 in Canada and 90 in the United Kingdom) received 2 doses of MenACWY-CRM at 2 and 4 months of age administered concomitantly with routine infant vaccines. At 12 months of age, the Canadian infants received either MenACWY-CRM or a reduced dose of a licensed meningococcal polysaccharide vaccine. In the United Kingdom, all infants received a further dose of MenACWY-CRM. The serological marker of protection was a titer of ≥1:4 using a serum bactericidal assay with human complement (hSBA).
Results: Two doses of MenACWY-CRM induced hSBA titers ≥1:4 in 57% (95% confidence interval [CI]: 45–67) and 50% (95% CI: 38–62) of infants against serogroup A in Canada and the United Kingdom, respectively, 93% (95% CI: 85–97) and 86% (95% CI: 46–93) against serogroup C, 95% (95% CI: 87–99) and 82% (95% CI: 71–90) against serogroup W-135, and 91% (95% CI: 82–96) and 74% (95% CI: 63–83) against serogroup Y. After a booster dose of MenACWY-CRM at 12 months, at least 94% of participants achieved hSBA titers ≥1:4 against each of the serogroups C, W-135, and Y and more than 79% against serogroup A. The vaccine was well tolerated.
Conclusions: The nonadjuvanted MenACWY-CRM is immunogenic and well tolerated in infancy and could provide broad protection against meningococcal disease in this vulnerable age group.
From the *Oxford Vaccine Group, and †Centre for Statistics in Medicine, University of Oxford, Oxford, UK; ‡Canadian Centre for Vaccinology, Dalhousie University and IWK Health Centre, Nova Scotia, Canada; §Canadian Center for Vaccinology, Dalhousie University and Queen Elizabeth II Health Sciences Center, Nova Scotia, Canada; ¶Novartis Vaccines and Diagnostics, Srl., Sie·na, Italy; and ∥Vaccine Evaluation Centre, British Columbia Children’s Hospital, Vancouver, British Columbia, Canada.
Accepted for publication September 16, 2008.
Supported by Novartis to attend scientific meetings (to K.P.P.); Wyeth Vaccines and Novartis Vaccines to attend conferences and has had travel and accommodation expenses paid by Novartis Vaccines while working with Novartis Vaccines in Siena, Italy (to M.D.S.); Wyeth to attend conferences (to T.J.); major vaccine manufacturers for performance of clinical trials (to J.L., S.M., S.D., and S.A.H.); employees of Novartis Vaccines and Diagnostics (to P.D., F.C., and A.A.); chief investigator for clinical trials conducted on behalf of Oxford University, sponsored by vaccine manufacturers (Novartis Vaccines, GlaxoSmithKline, Sanofi-Aventis, Sanofi-Pasteur MSD, and Wyeth Vaccines), and has received assistance from vaccine manufacturers to attend scientific meetings (to A.J.P.); industry-sourced honoraria 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, Oxford, United Kingdom. Supported by grants from the Novartis Vaccines and Diagnostics (formerly Chiron Vaccines). The sponsor (Novartis Vaccines and Diagnostics) was responsible for the development and manufacture of the study vaccine and for the development of the study protocol (with input from Drs Pollard, Halperin, and Dobson). The sponsor was responsible the initial data analysis, which was subsequently verified, who had full access to the study data (to L.Yu). Employees of the sponsor reviewed the manuscript before submission for publication. This work was supported by the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health’s NIHR Biomedical Research Centers funding scheme.
The views expressed in this publication are those of the authors and not necessarily those of the Department of Health. A.J.P. is a Jenner Institute Investigator. K.F. has no conflicts of interest to declare.
Study registered at clinicaltrials.gov: Identifier NCT00262002.http://clinicaltrials.gov/ct/show/NCT00262002?order=10.
Address for correspondence: Kirsten P. Perrett, MBBS, Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Centre for Vaccinology and Tropical Medicine, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, UK. E-mail: Kirsten.firstname.lastname@example.org.