title: The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines.
abstract: Major epidemics of serogroup A meningococcal meningitis continue to affect the African meningitis belt. The development of an affordable conjugate vaccine against the disease became a priority for World Health Organization (WHO) in the late 1990s. Licensing of meningococcal vaccines has been based on serological correlates of protection alone, but such correlates might differ in different geographical regions. If high pre-vaccination antibody concentrations/titers impacts on the response to vaccination and possibly vaccine efficacy, is not clearly understood. We set out to define the pre-vaccination Meningococcal group A (Men A) antibody concentrations/titers in The Gambia and study their impact on the immunogenicity of Men A containing vaccines. Data from subjects originally enrolled in studies to test the safety and immunogenicity of the MenA vaccine recently developed for Africa meningococcal A polysaccharide conjugated to tetanus toxoid, MenAfriVac(®) (PsA-TT) were analyzed. Participants had been randomized to receive either the study vaccine PsA-TT or the reference quadrivalent plain polysaccharide vaccine containing meningococcal groups A, C, W, and Y, Mencevax(®) ACWY, GlaxoSmithKline (PsACWY) in a 2:1 ratio. Venous blood samples were collected before and 28 days after vaccination. Antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) for geometric mean concentrations and serum bactericidal antibody (SBA) for functional antibody. The inter age group differences were compared using ANOVA and the pre and post-vaccination differences by t test. Over 80% of the ≥19 year olds had pre-vaccination antibody concentrations above putatively protective concentrations as compared to only 10% of 1-2 year olds. Ninety-five percent of those who received the study vaccine had ≥4-fold antibody responses if they had low pre-vaccination concentrations compared to 76% of those with high pre-vaccination concentrations. All subjects with low pre-vaccination titers attained ≥4-fold responses as compared to 76% with high titers where study vaccine was received. Our data confirm the presence of high pre-vaccination Men A antibody concentrations/titers within the African meningitis belt, with significantly higher concentrations in older individuals. Although all participants had significant increase in antibody levels following vaccination, the four-fold or greater response in antibody titers were significantly higher in individuals with lower pre-existing antibody titers, especially after receiving PsA-TT. This finding may have some implications for vaccination strategies adopted in the future.
authors.affiliation: Medical Research Council Unit, P.O. Box 273, The Gambia. Electronic address: oidoko@mrc.gm.
authors.forename: Olubukola T
authors.initials: OT
authors.lastname: Idoko
authors.affiliation: Jos University Teaching Hospital, P.M.B. 2084, Jos, Nigeria.
authors.forename: Seline N
authors.initials: SN
authors.lastname: Okolo
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, 1600 Clifton Rd, NE Atlanta, GA 30329, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Plikaytis
authors.affiliation: Medical Research Council Unit, P.O. Box 273, The Gambia.
authors.forename: Adebayo
authors.initials: A
authors.lastname: Akinsola
authors.affiliation: Meningitis Vaccine Project (MVP), PATH Europe, 13 Chemin du Levant, Bâtiment Avant-Centre, 01210 Ferney-Voltaire, France.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Viviani
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, 1600 Clifton Rd, NE Atlanta, GA 30329, USA.
authors.forename: George
authors.initials: G
authors.lastname: Carlone
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Findlow
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, 1600 Clifton Rd, NE Atlanta, GA 30329, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Elie
authors.affiliation: Serum Institute of India Ltd., 212/2, Hadapsar, 411028 Pune, India.
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Kulkarni
authors.affiliation: MVP, World Health Organization, 20 Avenue Appia, 1211 Geneva, Switzerland.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Preziosi
authors.affiliation: Medical Research Council Unit, P.O. Box 273, The Gambia; WHO regional Office for Africa, Brazzaville, Congo.
authors.forename: Martin
authors.initials: M
authors.lastname: Ota
authors.affiliation: Medical Research Council Unit, P.O. Box 273, The Gambia; Academic Department of Paediatrics, Imperial College London, London W2 1NY, UK.
authors.forename: Beate
authors.initials: B
authors.lastname: Kampmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000907:Antibodies, Bacterial / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005714:Gambia; D006801:Humans; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000627:therapeutic use*; D058248:Serum Bactericidal Antibody Assay; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; C573970:MenAfriVac; D022401:Meningococcal Vaccines
keywords: Antibody; Conjugate vaccine; Immune response; Meningococcal A; Pre-existing