Research ArticleVaccine Design

Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity

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Science Translational Medicine  13 Jul 2011:
Vol. 3, Issue 91, pp. 91ra62
DOI: 10.1126/scitranslmed.3002234

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All for One and One for All

The three musketeers were a formidable team, but imagine combining all of their skills and valor into just one musketeer. That is precisely the approach that Rappuoli and his colleagues have taken with their design of a vaccine against meningococcus B, the bacterial pathogen that causes meningitis. Although mining of the genome sequence of this pathogen has yielded excellent targets that could be used in a vaccine, many of these antigens show a high degree of variation that has stymied attempts to use them as vaccine immunogens. For example, factor H binding protein is essential for the survival of meningococcus B in the human host because it protects the pathogen from the onslaught of the human immune system’s complement pathway. Because it is essential for survival, factor H binding protein should be a valuable immunogen, but because it has at least 300 sequence variants, it is impractical to make one vaccine that contains all of these variants.

Rappuoli and his colleagues have tackled this problem by dividing the 300 sequence variants of factor H binding protein into three major groups. Using detailed structural information about these three major variants, they engineered variant 1 to carry patches of amino acids from the surfaces of variants 2 and 3. They then introduced groups of point mutations into the amino acids of these transplanted patches to mimic the natural variation of variant 2 and 3 strains of meningococcus B. They then tested which of the 54 engineered single chimeric immunogens could elicit bactericidal antibodies against many different strains of meningococcus B. To do this, they injected the immunogens into mice and assayed mouse sera in vitro for bactericidal activity against multiple bacterial strains. One chimeric immunogen, called G1, was capable of inducing bactericidal antibodies that could kill all strains of meningococcus B, suggesting that it could be used to produce a broadly protective vaccine. This structure-based approach to vaccine design may be useful not only for meningococcus B but also for other pathogens like HIV that show a high degree of antigenic variation.

Footnotes

  • * These authors contributed equally to this work.

  • Citation: M. Scarselli, B. Aricò, B. Brunelli, S. Savino, F. Di Marcello, E. Palumbo, D. Veggi, L. Ciucchi, E. Cartocci, M. J. Bottomley, E. Malito, P. Lo Surdo, M. Comanducci, M. M. Giuliani, F. Cantini, S. Dragonetti, A. Colaprico, F. Doro, P. Giannetti, M. Pallaoro, B. Brogioni, M. Tontini, M. Hilleringmann, V. Nardi-Dei, L. Banci, M. Pizza, R. Rappuoli, Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity. Sci. Transl. Med. 3, 91ra62 (2011).

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