Scientific basis of vaccines Flashcards
State the definition of a (prophylactic) vaccine?
A biological substance that does not cause disease, which, when administered to the recipient, produces an adaptive immune response which provides protection against future disease
What considerations should be taken for vaccine development?
- Protection (when + where)
- Type of immune cells required
- Site of immune response
Vaccine rationale
What can vaccines give protection to?
- Individual (prevention or decrease of disease)
- Populations (via herd immunity),
- Eradiation of disease
Describe and explain herd immunity?
- Majority of population are immune to disease
- Risk of spread from person to person decreased
- Those who are not immune are indirectly protected as ongoing disease spread is very small
- % of people who need to be immune in order to achieve HI varies with disease.
Explain the vaccine paradox with herd immunity?
- Herd Immunity memory boosted via periodic outbreaks of disease in community + vaccines
- As diseases rate decreased - no natural boosting -> increased importance of vaccination uptake rates -> Vaccine uptake rate = reservoirs of infection = risk to population + individual -> epidemic (decreased VUR)
Principles of vaccines
Describe the primary and secondary responses to antigens?
- Primary: 5-7 days - AB response -> 2 weeks for full response - IgM -> IgG switching + memory B + T cells
- Secondary: (prior A exposure) - < 7 days for full response
- Post exposure immunoprotection occurs -> response to specific antigens -> good targets for vaccines
State the general principles of vaccines?
- Induce correct type of response
- Response in right place
- Duration of protection
- Age of vaccination
Principles
State examples of the correct type of response principle for vaccines?
AB (polio) or cell mediated immunity (TB)
State examples of inducing response in the right place principle for vaccines?
- Mucosal (secreted IgA - influenza)
- systemic (yellow fever) -> Vaccines: parenteral (poor mucosal immunity)
- Oral (mucosal)
- Lymphoid tissue (MALT - good IgA production)
State examples of the duration of protection principle for vaccines?
- Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical, or radiation, and when symptoms and signs are first apparent.
- Short term - AB sufficient
- Long term - memory essential
- Boosters - natural (seasonal epidemics, carriage)
OR vaccines, type of infection - Long incubation time (systemic - measles)
- Short incubation time (surface - cholera)
State examples of the age of vaccination principle for vaccines?
- Maternal IgG AB enter foetus through placenta + slgA in breast milk -> provides weeks to months protection in neonate -> maternal AB may interfere with vaccine -> Optimum timing of vaccine determined via vaccination
Describe the difference between monotypic and polytypic pathogens and what type of immunity is involved with immunity?
- Monotypic: surface antigens always remain same (measles) - single vaccinations = lifelong immunity
- Polytypic: SA change + immunity readily overcome (antigenic drift) -> influenza
- Antigenic drift: accumulation of mutations in genes that code for virus surface proteins with time
Type of vaccines
State the 4 types of vaccines?
- Live Attenuated organism
- Killed whole organism
- Sub-unit
- Conjugated
Describe how live, attenuated organisms are formed for vaccine use and state example of these?
- ‘Passage’ (measles) -> serial culture in foreign host -> Organisms mutate + adapt to foregin host - decreased danger
- Chemical mutagenesis + selection of harmless phenotypes -> salmonella typhi TY21a
- Genetic engineering to create knockouts lacking genes for virulence (vibrio cholerae)
- e.g. BCG, polio (sabin), MMR, yellow fever, VZV)
Describe problems behind using Live attenuated organisms as vaccines?
- Vaccines pick up mutation - revert to virulence (polio)
- Require cold chain (refrigeration) to keep alive -> increased cost
- LA vaccines usefulness -> infect APC cells -> produce Tc memory cells
Killed whole-organism
Describe how a killed whole-organism is formed + features of its protective level compared with live attenuated?
- Killed with heat or chemicals (formalin or B-propiolactone) -> e.g. pertussis, influenza, poilio (salk type), cholera, HA
- Protective level: boosting often required -> LA vaccine has natural boosting via live organism
Sub-unit
Describe the sub-unit vaccines and examples of these?
Individual components of pathogen used -> proteins (surface A - hep B), toxoids, peptides (synthetic), polysaccharide
Describe the use of bacterial toxins as vaccines?
toxins - tissue damage + disease -> Convert to toxoids -> vaccine -> produces AB -> binds toxins - protect -> e.a. tetanus + diptheria
Why may subunit vaccines need to be boosted?
- Specific antigens may lack PAMPs (‹ danger signals),
- immune response may only be AB-mediated, not cell-mediated -> immune response weaker than others -> Increase immune response = use adjuvants or boosters
Define antigen drift and shift
- Antigenic drift: Accumulation of mutations in genes that code for virus surface proteins with time
- Antigenic shift: Recombination of viral strains to produce a different subtype with a mixture of surface antigens from the original strains
Conjugated
Describe the use of bacterial capsular polysaccharides as vaccines?
- Increased immunogenicity via protein conjugation (BCP + protein) -> protein carriers
- diptheria or tetanus toxoids or outer membrane proteins from bacteria (e.g. N.meningitidis) which are conjugated to polysaccharide capsule
-> long lasting immunity + response in children -> e.g. Neisseria meningitidis Group C, MenC vaccine, Haemophilus influenza Type B, Hib vaccine
Why is bacterial capsular polysaccharides not good to use alone?
- Poor antigens -> short term memory + no T-cell immunity
Describe conjugation + how they work?
- Link carrier protein with polysaccharide of bacteria -> Binds BCR -> presents protein + recognised via Th cell -> Cytokine release -> T helps B -> Increased immune response + good memory
Vaccine adjuvants
What are vaccine adjuvants, their advantages + example?
Chemical added to vaccines
- immunogenic
- Increase immune response to antigens
- Increase uptake + antigen presentation
- Stimulate correct cytokine profiles - e.g. aluminium salts (alum) -> form trapped particles (antigen) in depot -> slow antigen release -> Increase immune response + potent vaccine
Vaccination programmes
Describe components of a successful vaccination programme?
- Case findings (surveillance)
- Movement control
- Effective vaccine
Why is it difficult to produce a HIV vaccine?
- Increased mutation rate
- Danger of reversion to virulence (stops use ALV to induce Tc cells)
- Newer vaccine technology being used to develop
Describe passive treatments for vaccines?
- Maternal transfer, treatment with AB from another source - serum -> prophalyxis +/OR treatment -> Rapid short effect use
- Used for rabies -> human rabies immunoglobin or equine rabies Ig (horse serum) use
