In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study.
In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement.
Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5–38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series.
A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.
From the *Kaiser Permanente Vaccine Study Center, Oakland, CA; †Primary Physicians Research, Pittsburgh, PA; ‡Alabama Clinical Therapeutics, Pinson, AL; §Biostatistics, Novartis Vaccines and Diagnostics, Cambridge, MA; ¶Center for Global Health and Development, Boston, MA; and **Clinical Development, Novartis Vaccines and Diagnostics, Cambridge, MA.
Accepted for publication October 18, 2011.
Conflicts of interest and sources of funding: N.P.K supported by grants from Novartis, Pfizer, GlaxoSmithKline, Sanofi Pastuer, and Merck. W.J. supported by funds from Novartis for serving on a speaker bureau. N.P.K's and K.S.S's institutions are currently receiving grants from Novartis in support of this study. C.J.G. was employed by Novartis through 2010. T.O., L.B., and P.D. are currently employed by Novartis. Novartis paid for assistance in manuscript preparation. The authors have no other funding or conflicts of interest to disclose.
Address for correspondence: Nicola P. Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, 1 Kaiser Plaza, 16th Floor, Oakland, CA 94612. E-mail: Nicola.Klein@kp.org.