Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans — NEJM

Original Article

Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans
Samba O. Sow, M.D., Brown J. Okoko, M.D., M.P.H., Aldiouma Diallo, M.D., M.P.H., Simonetta Viviani, M.D., Ray Borrow, Ph.D., George Carlone, Ph.D., Milagritos Tapia, M.D., Adebayo K. Akinsola, M.D., Pascal Arduin, M.Sc., Helen Findlow, Ph.D., Cheryl Elie, M.Sc., Fadima Cheick Haidara, M.D., Richard A. Adegbola, Ph.D., F.R.C.Path., Doudou Diop, M.D., Varsha Parulekar, M.Sc., Julie Chaumont, M.Sc., Lionel Martellet, M.A., Fatoumata Diallo, M.D., Olubukola T. Idoko, M.D., Yuxiao Tang, Ph.D., Brian D. Plikaytis, M.Sc., Prasad S. Kulkarni, M.D., Elisa Marchetti, Ph.D., F. Marc LaForce, M.D., and Marie-Pierre Preziosi, M.D., Ph.D.

N Engl J Med 2011; 364:2293-2304June 16, 2011

Abstract
Background
Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed.


Methods
We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A–specific enzyme-linked immunosorbent assay.


Results
In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported. Conclusions The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine. (Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.) open here please: Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans — NEJM