Meningococcal disease and vaccines Flashcards
What is invasive MD defined as?
bacteria present in systemic circulation
How does invasive MD present as?
septicaemia and/or meningitis
What is the carriage rate of N. meningitides?
10-40%
Why is there a need for meningococcal vaccination?
non-specific early symptoms; rapid progression to disease; high fatality; serious sequelae
When do the peaks of MD typically happen and why?
after peaks of influenza- breach of respiratory epithelium allows MD?
Why does the ability of meningococcus to be invasive appear to be an accident?
cannot infect more people when invasive, kills off host- dead-end from evolutionary point of view of bacteria
What age group does MD mainly affect?
infants and young adults (biggest infectious killer of 1-5 yo)
Where are MD epidemics seen?
africa
What are the 5 major advances in meningococcal vaccine development?
recognition of serological correlate of problem; development of polysaccharide vacines; polysacchraride-conjugate vaccines; outer membrane vesicle vaccines; reverse vaccinology
What is mean by serological correlate of protection?
number of bactericidal antibodies present relates to meningococcal disease
How does the serological correlate of protection relate to the patients who get MD?
at around a year, babies have lost mothers antibodies and have not made their own yet–very susceptible
How is serum bactericidal activity used in vaccine development?
a way of measuring the success of vaccination
What is the quadrivalent polysaccharide vaccine?
agaisnt A, C, W135 and Y
What is the problem with the polysaccharide vaccines?
T-cell independent, short term protection and no immunological memory; response is age dependent and worse in <2 years when protection is needed most; no protection against colonisation
What carrier proteins was capsular polysaccharide attached to in Hib conjugate vaccine?
tetanus toxoid; CRM197
What is CRM197?
mutant diphtheria toxin
What is the result of conjugate polysaccharide vaccines vs polysacchraide?
T-cell dependent response; immunological memory and prolonged protection; good response in infants; prevents colonisation
What serogroup of meningitis affects the african meningitis belt previous to menafrivac?
A
Which serogroups share the same sugar in the capsule and what differs?
B- a2-8 branching structure whereas C has an a2-9 branching structure
What is the problem with serogroup B capsule?
poor immunogen but mostly that it shares structures with host cell neural cell adhesion molecules- risk of autoimmunity
What were the proposed possibilities for developing non-capsular antigens for serogroup A?
outer membrane vesicle vaccines; reverse vaccinology
What are OMVs??
blebs released spontaneously by growing meningococci that contains outer membrane proteins; lipids and LPS
What is the problem with OMV vaccines?
are strain specific rather than covering hte whole serogroup
What protein is mainly targeted in OMV vaccines?
PorA protein- which is antigenically variable
What are the potential solutions to issues with OMV vaccines?
use genetically engineered strains which express more than PorA type and which over-express other outer membrane antigens – this has not been very successful
Why is a B cells response to capsular polysaccharide T cell independent?
cannot be loaded onto MHC complexes
How does reverse vaccinology being?
by sequencing the genome of hte pathogen and using a computer to predict the proteins produced by the pathogen
What are the criteria for choosing a protein as a vaccine candidate?
not variable- not pilli or porA; expressed on OM; immunogenic
What important protein was discovered by reverse vaccinology?
factor H binding protein
