8 Defence and Vaccination Against Bacteria Flashcards
Q: Describe innate immunity. Requires? Speed? Mediated by? Initially?
A: -First line of defence
- Does not require exposure to the infectious agent
- Is immediate (almost)
- Mediated by (cells of the immune system) monocytes and polymorphonuclear PMNs
- Initially an inflammatory reaction
Q: Acquired immunity. Requires? Speed? Mediated by? (2)
A: -Requires exposure to infectious agents
- Takes time to develop
- Mediated mainly by lymphocytes (B and T cells)
- Other cell types involved, e.g. monocytes and dendritic cells
Q: Humoral immunity. Mediated by? from? (2)
A: -directly mediated by antibodies
- antibodies are produced by B lymphocytes
- Plasma cells (terminally differentiated B lymphocytes) are the primary source of secreted immunoglobulins/ antibodies
Q: What does not mediate cell mediated immunity.? Instead? (2) What’s the role of cell mediated immunity? examples (3). What’s key to the clearance of infection?
A: -not primarily mediated by antibody
- mediated by T lymphocytes and natural killer NK cells
- indirectly other cell types may play a role e.g. macrophages
- eliminating intracellular bacteria, e.g. tuberculosis, typhoid, legionella
- interaction of the reactive T lymphocytes and the macrophage
Q: How can the role of antibodies vary? 3 methods. 4 example bacterium.
A: depending on the disease itself
- Toxin neutralisation, e.g. tetanus, diphtheria, botulism, anthrax etc.
- As a focus for complement binding
- As an opsonin promoting phagocytosis
Q: In reality, the best protection will often be the result of?
A: a combination of humoral and cell mediated immunity
Q: Describe the ideal vaccine. (6)
A: -Stimulates an effective immune response
- safe and does not cause adverse reactions
- inexpensive to manufacture and distribute
- stable to aid distribution
- easy to administer
- simple for both manufacturer and regulatory authorities to control
Q: What are the different forms of protection you get from vaccines? (2)
A: -direct protection
-herd immunity
Q: What occurs in direct protection? (2)
A: immunise person and other them protection against the invasive process but doesn’t stop cycle of release and acquisition/ circulation
Q: What is herd immunity? What type of protection is this?
A: immunising a few people to protect the majority
-indirect protection where cycle of transmission is stopped
Q: How is vaccine safety and efficacy (producing desired result) assessed? What is involved?
A: clinical trials, have 3 phases
Q: What are phase 1 clinical trials used for? (2) Participants?
A: -Primarily for safety but are often also used to assess immunogenicity
-Usually small numbers of adults
Q: What are phase 2 clinical trials used for? (2) Participants? (2)
A: -Primarily for assessing immune response but also used to expand safety database
-Typically includes all groups that are likely to use the vaccine- larger number of people
Q: What are phase 3 clinical trials? Design? (2) What do they require? (3) What is the end goal to provide?
A: -Protection studies,
-usually placebo controlled double blind trials
- Require good disease surveillance
- case ascertainment
- definition of endpoint
provide statistically conclusive data for licensure
Q: In what phase clinical trial is efficacy determined? describe (2). Equation? Expressed?
A: Phase III trials- blinded, placebo controlled
attack rate in vaccinated group = 1 - ------------------------------------------------
attack rate in unvaccinated group
percentage
Q: What is the equation that relates the basic reproduction number R0, vaccine effectiveness and coverage needed to reduce or eliminate disease?
A: 1
1 - ————
R0
vaccine coverage = ———————-
effectiveness
Q: When is the herd effect determined? Equation?
A: post vaccine introduction
attack rate unvaccinated post-introduction = 1 - --------------------------------------------------------------
attack rate unvaccinated pre-introduction
Q: What are the constituents of a vaccine? (3) What are their functions? (1,1,4) (3 includes 6 examples).
A: Antigen- stimulate immune response to target disease
Adjuvant (in some)- enhance and modulate immune response
Excipients- Buffer, salts, saccharides and proteins to maintain the pH, osmolarity and stability of the vaccine
-Preservative, e.g. phenoxyethanol, thiomersal (not used so much anymore)
Q: What are the options for vaccine antigens? (5) How do they differ?
A: -Live attenuated organisms
-Killed whole organisms
=> complex, multiple antigens, ill defined
-Purified component vaccines
- Toxoids
- Polysaccharide conjugates
=>individual or small number of well defined antigens
Q: When does the UK childhood immunisation programme start? Summarise what is involved. When are the next set of vaccines?
A: 2 months
sets of vaccines at 2, 3, 4 and 12 months (4,2,3,4)
3 years and 4 months onwards
Q: Which vaccines are given at 2 months?
A: -rotavirus
- MenB
- Pneumococcal conjugate
- DTaP-Hib-IPV
Q: Which vaccines are given at 3 months?
A: -rota virus
-DTaP-Hib-IPV
Q: Which vaccines are given at 4 months?
A: -MenB
- Pneumococcal conjugate
- DTaP-Hib-IPV
Q: Which vaccines are given at 1 year?
A: -MenB
- Pneumococcal conjugate
- Hib + MenC booster
- MMR
Q: Which vaccines are given 3 years and 4 months on? (6)
A: -pre primary school: DTaP-IPV booster, MMR booster
- live attenuated influenza vaccine
- girls 12-13 years are given HPV
- during secondary school: dT-IPV booster, MenACYW
Q: What does the DT in DTaP-Hib-IPV stand for? What method is used to treat? Describe the vaccine. (6)
A: Tetanus and diphtheria toxoids
-chemical inactivation of bacterial exotoxin via neutralisation
- Simple to produce
- Relatively pure
- Safe
- High protective efficacy
- very immunogenic
- appropriate immune response i.e. toxin neutralizing antibodies block activity
Q: What does the aP in DTap-Hib-IPV stand for? What is the disease? Which bacteria causes it? how? (2) Characterised by? What does recovery coincide with?
A: acellular pertussis
-Whooping cough
Bordetella pertussis
- infecting ciliated epithelium
- and releasing toxin
Condition identified by characteristic convulsive cough
antibody production
Q: What was the early vaccine for Bordetella pertussis? Effectiveness? Associated with? (4) Current vaccine? development was driven by?
A: (whooping cough)
Whole cell pertussis vaccine
effective -> efficacy rates typically >90%
associated with a number of adverse reactions
- anaphylaxis
- prolonged crying
- febrile siezures
- acute encephalopathy (now known to be due to mutations within a sodium channel gene)
Development of acellular (component) vaccine driven by poor acceptance of the whole cell vaccine
Q: What could make up the B. pertussis component vaccine? (3)
A: lots of potential antigens
- Antigens that attach to ciliated epithelium
- Antigens that adhere and complement resistance
- Toxins
Q: What is the current vaccine for whooping cough? Made of? Compared to old one? Efficacy? Problem that arose? Solution? 2 questions that were asked.
A: Acellular vaccine against Bordetella pertussis
- multicomponent (bi-,tri- and pentavalent fromulations)
- safe and efficacious (75-90%)
10 deaths in newborns in 2012
-pregnant women were offered vaccination in third trimester= effective
- additional booster needed?
- improved vaccine needed?
Q: What does Hib stand for in DTap-Hib-IPV? What does this cause? (2) What is the vaccine targeted at? downside? Vaccine type?
A: -H. influenzae type b
-meningitis and septicaemia in the young
-capsule that protects organisms but it is made of polysaccharides = poorly immunogenic (polyribosyl-ribitol phosphate capsule)
The Hib component is a conjugate vaccine
Q: Hib vaccine effectiveness? 10 years later?
A: very effective
booster introduced after cases increases
Q: What is the main paediatric combination vaccine? What does it contain? (6) Examples? (2)
A: Antigens: -Tetanus toxoid -Diptheria toxoid -Pertussis components: -Hib PRP-conjugate -Inactivated polio virus types 1,2 and 3 Adjuvant: aluminium phosphate
Pediacel® (Sanofi) and Infanrix® (GSK)
Q: What type of antigens are polysaccharides? Structure? (3) Good at? how? Resulting immune response is ideal for? why? Characterised by? (2)
A: T cell independent antigens
-Usually large and linear and repetitive
-stimulating B cells (when they bind to Ig receptors on B cell surface) in the absence of antigen presentation, by cross-linking immunoglobulin receptors on the cell surface
The resulting immune response is not ideal for vaccination.
-in many cases repeated doses rather than boosting can lead to immunological hyporesponsiveness
- poor immunological memory
- low avidity antibodies (no affinity maturation- Predominantly IgM) that are less likely to offer functional protection against disease,
Q: What are conjugate vaccines based on? Requires? Result? examples (3). Benefits? (5)
A: Polysaccharide chemically linked to immunogenic protein
Sophisticated technology= expensive
Highly purified components
purified saccharide and carrier proteins such as tetanus toxoid, diphtheria toxoid or CRM197
- safe
- simple for licensure and control
- Very effective when humoral immunity is required
- long-lived, boostable immunity
- reduce carriage i.e. offer herd immunity
Q: What are the 3 ways to prepare a conjugate vaccine? How do the results vary?
A: Random activation of high molecular weight or partly size reduced polysaccharide
Degradation of the polysaccharide to form active functional groups at both terminals
Degradation of the polysaccharide to form active functional group at only one terminal
vary in size. (largest at top to smallest)
Q: How do conjugate vaccines interact with T cells? What does this require? Explain. What else is activated? what do they do?
A: Naive T cells primed by interaction with vaccine conjugate through interaction with antigen presenting cells
Requires antigenic stimulation via MHCII-TCR pathway
- Saccharide specific B cells take up conjugate and present the carrier peptides to T cells via MHCII
Activated B cells differentiate into antibody secreting plasma cells and memory B cells
Q: Name currently licensed conjugate vaccines. (5) Future?
A: -Hib vaccine
- Pneumococcal conjugates
- MenC conjugates
- MenC+Hib booster - Menitorix
- Meningococcal A, C, W, Y conjugates
In the future Group B streptococcal vaccines (treat neonatal meningitis and septicaemia in new borns
Q: Describe the mass vaccination programme for MenC in the UK. Result? (against?) Overall? What was needed later?
A: used conjugate vaccine and targeted high risk age groups over the years (risk group changed as population was treated)
seen to be very effective as incidence decreased for that serogroup
serogroup C meningococcal infections
other age groups that weren’t immunised showed decreased incidence-> shows herd immunity
booster (MenC)
Q: What do conjugate vaccines promote?
A: Promotes efficient antibody response to polysaccharide capsule
Q: What does Streptococcus pneumoniae cause? (3) Serotypes? Problem? What are the 2 vaccines for it? What did clinical trials show?
A: -meningitis
- septicaemia
- mucosal infections, e.g. pneumonia and otitis media
More than 90 serotypes determined by capsular polysaccharide -> antibiotic resistance associated with some serotypes
- Pneumovax II™, 23-valent plain (unconjugated) polysaccharide vaccine -> only effective in adults
- Prevenar 7™, Prevenar 13™ and Synflorix™ conjugate vaccines -> clinical trails showed to be effective
Q: Describe the occurrence of pneumococcal disease after the introduction of Prevenar 13. Possible solution?
A: incidence of unvaccinated serotypes increased despite vaccinated ones decreasing
using protein based vaccines instead
Q: What do vaccines against group B meningococcal disease target? Reason?
A: outer membrane vesicles (OMV) that are released spontaneously by them in vivo and in culture and they contain all the protein antigens usually associated with the outer membrane
Men B capsule contains polysaccharides (unlike MenC) that are similar to ours= not good (almost seen as self)
Q: What are the vaccine against group B meningococcal disease? How is it made? Safety aspect step? When are these vaccines useful? Downside?
A: outer membrane vesicle vaccines
Vaccines are produced by detergent extraction to reduce endotoxin content -> turn into safe vaccine
Hyper-producing mutants have been isolated
- only offer good protection against the homologous strain in single outbreaks
- not good for epidemics with multiple strains
Q: How were new MenB vaccines produced? Result? What do they now target?
A: ‘reverse vaccinology’ approach
instead of pasteurs principle of isolate inactivate and inject, they started from the genomic sequence and used computer predictions to express possible recombiant proteins etc
3 additional antigens were identified
- Factor H binding protein (fHbp)
- Neisseria adhesin (NadA)
- Heparin binding protein (Nhbp)
-OMV and above
Q: What is the vaccine against tuberculosis? How? Result? (2)
A: (BCG) = live attenuated strain of Mycobacterium bovis
Serial passage, 231 times over 13 years (1908-1921)
- Phenotypic changes: rough/dry to moist/smooth
- Genotypic changes: loss of RD1 region encoding 9 proteins (we figured out now)
Q: How does the BCG work? What did it do when it was first introduced? (2) What are the new vaccines?
A: (vaccination for tuberculosis)
Cannot be answered definitively as programmes instituted at the same time as social, economic and public health improvements
Generally accepted that it prevents severe childhood TB and leprosy
New candidate vaccines are in the research pipeline
recombinant modified vaccinia virus expressing antigen 85A
Q: What is typhoid caused by? Transmission? What are the 2 vaccines for it? (type, isolation by, offered to, suitable for). What’s in development?
A: Typhoid, or enteric fever, is caused by the bacterium Salmonella enterica servar typhi. It is transmitted by the ingestion of faecally contaminated food or water.
Vivotif ® live attenuated vaccine
-isolated by chemical (NTG) mutagenesis
Vi polysaccharide
- Offered to those travelling to typhoid endemic areas
- Only suitable for >2 year olds
- Conjugates in development
Q: What are the 3 cholera vaccines? Describe them.
A: -Killed whole cell parenteral vaccine
- poor efficacy
- short-lived protective response
- strain specific
Killed whole cell oral vaccine
- good efficacy in cholera endemic area (Vietnam trials)
- safe
Dukoral™
- killed whole cell + CtxB oral vaccine
- drink formulation (3 doses at weekly intervals, booster every 2 years)
- may also protect against ETEC
Q: What do adjuvants do? What are the 2 categories they fall into? examples (4,5).
A: potentiate the immune response (humoral, cellular or both)
-Delivery systems, usually a depot of antigen which is slowly released eg mineral salts, synthetic microparticles, oil-water emulsions, liposomes
Immune potentiators that are recognised as bacterial components and elicit inflammatory/ innate immune response eg Toxins and lipids, Peptidoglycan, Cytokines and hormones
Q: What are immune potentiators also called? Detected by? result? Specificity?
A: PAMPs- Pathogen Associated Molecular Pattern
Pattern recognition receptors (PRRs) bind microbial PAMPs and stimulate the immune response
can elicit specific responses by targeting different receptors
Q: What must you do when considering to get the immunosuppressed vaccinated? What do you need to consider? How can it be achieved? What does the decision to vaccinate depend on?
A: risk benefit analysis- Live vaccines need particular consideration
Need to protect the vulnerable patient
- Public health perspective (herd immunity)= v important
- Protect the patient by immunising close contacts
nature of the immunodeficiency and the vaccine
