title: Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda.
abstract: BACKGROUND
  Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine.
  
  
  RESULTS
  We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a > or =4-fold increase in SBA against a target strain from each serogroup and SBA titer > or =128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies.
  
  
  CONCLUSIONS
  While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa, the use of 1/5 fractional doses should be considered as an alternative in mass vaccination campaigns.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00271479.
authors.affiliation: Epicentre, Paris, France. philippe.guerin@epicentre.msf.org
authors.forename: Philippe J
authors.initials: PJ
authors.lastname: Guerin
authors.forename: Lisbeth M
authors.initials: LM
authors.lastname: Naess
authors.forename: Carole
authors.initials: C
authors.lastname: Fogg
authors.forename: Einar
authors.initials: E
authors.lastname: Rosenqvist
authors.forename: Loretxu
authors.initials: L
authors.lastname: Pinoges
authors.forename: Francis
authors.initials: F
authors.lastname: Bajunirwe
authors.forename: Carolyn
authors.initials: C
authors.lastname: Nabasumba
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Leif O
authors.initials: LO
authors.lastname: Frøholm
authors.forename: Salah
authors.initials: S
authors.lastname: Ghabri
authors.forename: Vincent
authors.initials: V
authors.lastname: Batwala
authors.forename: Rogers
authors.initials: R
authors.lastname: Twesigye
authors.forename: Ingeborg S
authors.initials: IS
authors.lastname: Aaberge
authors.forename: John-Arne
authors.initials: JA
authors.lastname: Røttingen
authors.forename: Patrice
authors.initials: P
authors.lastname: Piola
authors.forename: Dominique A
authors.initials: DA
authors.lastname: Caugant
mesh_terms: D000293:Adolescent; D017954:Africa South of the Sahara / Q000453:epidemiology; D000818:Animals; D001428:Bacterial Vaccines / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008585:Meningitis, Meningococcal / Q000453:epidemiology / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000627:therapeutic use*; D011817:Rabbits; D012449:Safety; D016037:Single-Blind Method; D014454:Uganda / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001428:Bacterial Vaccines; D011135:Polysaccharides, Bacterial; D003165:Complement System Proteins