A STRUCTURAL EXPLANATION OF THE IMPORTANCE OF ACETYLATION IN NEISSERIA MENINGITIDIS SEROGROUP. A CAPSULAR POLYSACCHARIDES TO RAISE FUNCTIONAL ANTIBODIES

摘要

Meningococcus remains a devastating cause of meningitis epidemics and sepsis, with more than one million cases resulting in approximately 135,000 deaths reported annually worldwide with a fatality rate of 20% in developing countries [1]. Neisseria meningitidis serogroup A (MenA) is a Gram-negative encapsulated bacterium responsible for epidemic meningitis in the sub-Saharan region of Africa, termed meningitis belt [2]. Multivalent conjugate vaccines containing also MenA capsular polysaccharide are now available in western countries, and their efficacy in preventing infection in humans is well established. In a surveillance study monitoring the introduction of vaccination with the conjugate vaccine MenAfriVac (specific for serogroup A) in the meningitis belt, a 57% of decline in incidence was recorded [3]. MenA capsular polysaccharide (CPS) consists of (1->6) linked 2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units with O-acetylation predominantly at position 3 [4]. Two parameters influence the immunogenicity of MenA conjugates: the oligomer length and the acetylation level [5]. Moreover, MenA glycoconjugate vaccines have a poor hydrolytic stability [6]. Although a conjugate vaccine containing MenA oligosaccharides with an average chain length of six was immunogenic in adults [7], the minimal antigenic determinant of MenA polysaccharide is still unknown. Therefore molecular understanding antigen-antibody interactions is crucial to reveal the minimal structural requirements for the vaccines immunological activity and the rationale for a more stable MenA vaccine based on glycan mimetics.