Meningococcal disease and vaccines

Question 1

What is invasive MD defined as?

Answer 1

bacteria present in systemic circulation

Question 2

How does invasive MD present as?

Answer 2

septicaemia and/or meningitis

Question 3

What is the carriage rate of N. meningitides?

Answer 3

10-40%

Question 4

Why is there a need for meningococcal vaccination?

Answer 4

non-specific early symptoms; rapid progression to disease; high fatality; serious sequelae

Question 5

When do the peaks of MD typically happen and why?

Answer 5

after peaks of influenza- breach of respiratory epithelium allows MD?

Question 6

Why does the ability of meningococcus to be invasive appear to be an accident?

Answer 6

cannot infect more people when invasive, kills off host- dead-end from evolutionary point of view of bacteria

Question 7

What age group does MD mainly affect?

Answer 7

infants and young adults (biggest infectious killer of 1-5 yo)

Question 8

Where are MD epidemics seen?

Answer 8

africa

Question 9

What are the 5 major advances in meningococcal vaccine development?

Answer 9

recognition of serological correlate of problem; development of polysaccharide vacines; polysacchraride-conjugate vaccines; outer membrane vesicle vaccines; reverse vaccinology

Question 10

What is mean by serological correlate of protection?

Answer 10

number of bactericidal antibodies present relates to meningococcal disease

Question 11

How does the serological correlate of protection relate to the patients who get MD?

Answer 11

at around a year, babies have lost mothers antibodies and have not made their own yet–very susceptible

Question 12

How is serum bactericidal activity used in vaccine development?

Answer 12

a way of measuring the success of vaccination

Question 13

What is the quadrivalent polysaccharide vaccine?

Answer 13

agaisnt A, C, W135 and Y

Question 14

What is the problem with the polysaccharide vaccines?

Answer 14

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

Question 15

What carrier proteins was capsular polysaccharide attached to in Hib conjugate vaccine?

Answer 15

tetanus toxoid; CRM197

Question 16

What is CRM197?

Answer 16

mutant diphtheria toxin

Question 17

What is the result of conjugate polysaccharide vaccines vs polysacchraide?

Answer 17

T-cell dependent response; immunological memory and prolonged protection; good response in infants; prevents colonisation

Question 18

What serogroup of meningitis affects the african meningitis belt previous to menafrivac?

Answer 18

A

Question 19

Which serogroups share the same sugar in the capsule and what differs?

Answer 19

B- a2-8 branching structure whereas C has an a2-9 branching structure

Question 20

What is the problem with serogroup B capsule?

Answer 20

poor immunogen but mostly that it shares structures with host cell neural cell adhesion molecules- risk of autoimmunity

Question 21

What were the proposed possibilities for developing non-capsular antigens for serogroup A?

Answer 21

outer membrane vesicle vaccines; reverse vaccinology

Question 22

What are OMVs??

Answer 22

blebs released spontaneously by growing meningococci that contains outer membrane proteins; lipids and LPS

Question 23

What is the problem with OMV vaccines?

Answer 23

are strain specific rather than covering hte whole serogroup

Question 24

What protein is mainly targeted in OMV vaccines?

Answer 24

PorA protein- which is antigenically variable

Question 25

What are the potential solutions to issues with OMV vaccines?

Answer 25

use genetically engineered strains which express more than PorA type and which over-express other outer membrane antigens – this has not been very successful

Question 26

Why is a B cells response to capsular polysaccharide T cell independent?

Answer 26

cannot be loaded onto MHC complexes

Question 27

How does reverse vaccinology being?

Answer 27

by sequencing the genome of hte pathogen and using a computer to predict the proteins produced by the pathogen

Question 28

What are the criteria for choosing a protein as a vaccine candidate?

Answer 28

not variable- not pilli or porA; expressed on OM; immunogenic

Question 29

What important protein was discovered by reverse vaccinology?

Answer 29

factor H binding protein