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A Randomized Controlled Trial in Chile

Jordan W. Tappero, MD, MPH; Rosanna Lagos, MD; Aurora Maldonado Ballesteros; Brian Plikaytis, MSc; Derrick Williams, BS; Janet Dykes, BA; Linda L. Gheesling, BS; George M. Carlone, PhD; E. Arne Høiby, MD; Johan Holst, MSc; Hanne Nøkleby, MD; Einar Rosenqvist, PhD; Gustavo Sierra, MD; Concepción Campa, MD; Franklin Sotolongo, PhD; Jeanette Vega, MD; Julio Garcia, MD; Patricio Herrera, MD; Jan T. Poolman, PhD; Bradley A. Perkins, MD

JAMA. 1999;281:1520-1527.

Context  Meningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group.

Objective  To evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy.

Design  Double-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994.

Setting  Santiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993.

Participants  Infants younger than 1 year (n=187), children aged 2 to 4 years (n=183), and adults aged 17 to 30 years (n=173).

Intervention  Participants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3.

Main Outcome Measure  Immune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer.

Results  Children and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen.

Conclusions  These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain–specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.

Author Affiliations: Centers for Disease Control and Prevention, Atlanta, Ga (Drs Tappero, Carlone, and Perkins, Messrs Plikaytis and Williams, and Mss Dykes and Gheesling); Hospital Roberto del Río (Dr Lagos), Centro para Vacunas en Desarrollo-Chile (Dr Lagos), Instituto de Salud Publica (Ms Ballesteros and Dr Garcia), Pan American Health Organization (Dr Vega), and the Universidad de Chile (Dr Herrera), Santiago, Chile; National Institute of Public Health, Oslo, Norway (Drs Høiby, Nøkleby, and Rosenqvist and Mr Holst); Finlay Institute, Havana, Cuba (Drs Sierra, Campa, and Sotolongo); and the Laboratory for Vaccine Development and Immune Mechanisms, National Institute for Public Health and Environmental Protection, Bilthoven, the Netherlands (Dr Poolman). Dr Poolman is now with SmithKline Beecham Biologicals, Rixensart, Belgium.

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