The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis?

Abstract

The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci.

Keywords: Haemophilus influenzae; Neisseria meningitidis; Streptococcus pneumoniae; herd immunity; population biology; vaccines.

Figure 1.

Evolution of meningococcal disease in the US Army in the Vietnam War era. The disease outbreak was predominantly caused by sulphonamide-resistant organisms belonging to the ST-11 (ET-37 complex), with a capsule replacement event that replaced sulfonamide-resistant serogroup B meningococci with sulfonamide-resistant serogroup C organisms. Plain polysaccharide vaccines against serogroup C were introduced in 1971, against serogroup C and A in 1978, and against serogroups A, C Y and W in 1982. Data compiled from Brundage & Zollinger [45] and Wang et al. [50]. NG, not-groupable isolates.

Figure 2.

The number of laboratory confirmed cases of meningococal disease in England and Wales before and after the introduction of MCC vaccines in autumn 1999. Drawn with data from Gray et al. [71] and the UK Health Protection Agency (http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/MeningococcalDisease/EpidemiologicalData/). Ungroupable isolates were those samples for which no serogroup could be obtained (e.g. as a result of non-culture diagnosis without serogroup determination).

Figure 3.

The fate of the epidemic meningococcal strain serogroup C, ST-11 complex, in carriage by UK teenagers (aged 15–19 years) before (1999) and for two years subsequent to the introduction of MCC vaccines in the UK [86,87]. Black represents ST-11 complex meningococci that were expressing their capsule and white indicates ST-11 complex isolates that contained the serogroup C capsular region but did not express it. Note the very low rates of carriage of the epidemic strain even before vaccine introduction.