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Meningococcal vaccines: Advances but new questions?

fulminant presentations, attracts considerable medical, media and public attention. The disease affects all ages, but has its highest incidence in infants and adolescents. The mortality, even in what is otherwise usually a healthy population, remains at approximately 10%, a factor that provokes both emotion and a search for better individual management and community based interventions. The epidemiology of IMD and disease outcome in infected individuals may be materially affected by the characteristics of the causative organism and the host response is also a significant determinant of mortality and morbidity. Antibodies to capsular polysaccharides are the major factor in protection against IMD.1 However, strategies aimed at inducing a protective level of capsular antibody by vaccination suffer from a number of limitations. Serogroup B meningococcal infection, the most common type in Australia, is not prevented by this means, probably because of immune tolerance; the group B capsular polysaccharide is identical to cell-surface polysaccharides in the developing brain.2 In contrast, polysaccharide vaccines have been available for some time for meningococci of serogroups A, C, Y and W135, either as bivalent (A plus C) or quadrivalent options. For these vaccines, the combined problems of a lack of immunogenicity in the very young, in whom the disease is most prevalent, and poor memory response (similar to that identified with pneumococcal and Haemophilus influenzae type b (Hib) polysaccharide vaccines2) limit their application essentially to the control of defined outbreaks. These problems have seen investigation into the use of outer membrane protein and other non-capsular antigens as vaccine candidates, especially for serogroup B infection, and conjugated polysaccharide group C vaccines have now been widely used in the UK. Given the extremely high rates of epidemic group A disease that exist, most obviously in subSaharan Africa, the greatest global need would seemingly be for a group A conjugate vaccine, but this prospect seems some way off. The UK approach to the use of the serogroup C conjugate vaccine raises a number of questions pertinent to the use of vaccines for the prevention of IMD in Australia and these are examined in a series of papers in this issue. The meningococcus is a strictly human pathogen with a very narrow habitat range. Serogroup A organisms stand out as a ‘clonal’ and epidemicinducing subset of meningococci, but have not been seen in Australia for many years. The survival of meningococci other than those of serogroup A seems to depend on their capacity for colonization of and transmission between mucosal membranes and their ability to evade or neutralize host mucosal defences. To achieve this, the meningococcus displays a genetic diversity rarely seen in other human pathogens. This is accomplished mainly by horizontal genetic transfer, but also by recombination of repeat genetic sequences within the genome. ‘Successful’ recombination events see the appearance of new subtypes that may become prevalent, whereas an ‘unsuccessful’ change does not survive. Therefore, invasive meningococci appear to arise from chance recombination events linking successful transfer and colonization characteristics with virulence features in the one organism. There is also evidence that capsule switching probably occurs in vivo, at least between serogroup C and B meningococci, and indeed may be common when carriage of both serogroups occurs simultaneously.3 This capacity for recombination in meningococci should introduce some wariness in the widespread application of vaccination against a single capsular type. This and other considerations, such as the effect of vaccination on meningococcal throat carriage, are part of the continuing evaluation of the UK vaccination project. In their contribution, Pollard and Scheifele4 discuss the considerable variation in the distribution of invasive meningococcal subtypes in North America. They also note the particular diversity of group B subtypes recorded in a number of studies. It has been estimated that the 20 most common serogroup B phenotypes in the US account for only 60% of serogroup B strains there. While Pollard and Scheifele4 see the conjugate serogroup C vaccine as providing an opportunity to decrease the already low disease rate in the US, they also caution that the predominant group B organisms ‘. . . could take up the ecological niche vacated by vaccine strains’. Evidence from Hajj-associated disease in 2000, whereby serogroup W135 cases have increased following use of bivalent A/C polysaccharide vaccine, indicates that strain replacement (without the need to postulate genetic recombination) does J. Paediatr. Child Health (2001) 37, S1–S2