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.

Towards the endgame and beyond: complexities and challenges for the elimination of infectious diseases

“…In 2010 and 2011 more than 55 million persons aged 1 to 29 years in Burkina Faso, Mali and Niger received conjugate vaccine that reduces carriage and transmission. It is thought that high coverage in this age group can eliminate meningococcal A epidemics in sub-Saharan Africa, but the main challenges are achieving and maintaining vaccine coverage [24]. …”

Genetic and Molecular Basis of Kingella kingae Encapsulation

“…Polysaccharide conjugate vaccines based on the capsular polysaccharides of Neisseria meningitidis, Haemophilus influenzae type b, and Streptococcus pneumoniae have dramatically reduced morbidity and mortality worldwide (5). The development of these vaccines has been among the most successful public health innovations of the last 25 years (6).…”

A Synthetic Disaccharide Analogue from Neisseria meningitidis A Capsular Polysaccharide Stimulates Immune Cell Responses and Induces Immunoglobulin G (IgG) Production in Mice When Protein-Conjugated

“…6 In addition, these vaccines are not easy to handle and not fully effective, as demonstrated by the meningococcal epidemics still occurring in Africa. 7 Exceptions among carbohydrate immunogens are some zwitterionic polysaccharides (ZPS), that are, bacterial polysaccharides containing both positive and negative charge centers within a repeating unit. ZPS behave like traditional T cell-dependent antigens, triggering in vitro antigen presenting cells (APC) and CD4 + T cells through TLR2-and MHC IIdependent pathways.…”