Scientific Basis of Vaccines Flashcards
Describe the relation between smallpox and cowpox
- Smallpox virus (variola virus)
- Milkmaids that had cowpox never got smallpox and could not be variolated
- Variola caused smallpox
- If you inoculated someone with a lesion from someone who was recovering from smallpox, they would recover
Define Variolation
Variolation is inoculation with materials from infected individual (pus).
Describe jenners observed principles
- Challenge dose – proves protection from infection. Proves that the vaccine is working.
- Concept of attenuation something weakened may give you protection
- Concept that prior exposure to agent boosts protective response
- Cross-species protection – antigenic similarity
How and why was smallpox eradicated?
How?
- Vaccination programmes
- case finding (surveillance) and movement control
Why possible?
- No sub-clinical infections
- After recovery, the virus was eliminated - no carrier states
- No animal reservoir
- Effective vaccine (live vaccinia virus)
- Slow spread, poor transmission
Define vacccine
What does it produce?
Does it prevent disease?
What does it lead to?
Vaccine: material from an organism that will actively enhanced adaptive immunity.
• It produces an immunologically primed state that allows of a rapid secondary immune response on exposure to an antigen
• Its prevents disease but not infection
• Long lasting – requires immunological memory
• Leads to T-cell memory or antibodies
Describe the rationale behind vaccines
- Protects the individual by reducing rate and severity.
- Protects population through herd immunity.
- Eradicates the disease.
- Take into account reservoirs of infection and vaccine uptake rate.
- Balance risk to individual against risk to population.
- Prevention of epidemics.
- Rubella is a mild disease to vaccine is not to protect population but to prevent congenital damage.
Describe the vaccine paradox
- Herd immunity- memory boosted by periodic outbreaks of disease in the community.
- As rates of disease decline, there is no natural boosting.
- This then increases the importance of vaccination take up rates.
What are the two types of immunity?
- Active- natural exposure, infection or vaccination and has long-term effect.
- Passive- naturally acquire antibodies through placenta/breastmilk. Due to prophylaxis and/or treatment. Short effect.
- In first world war, horse anti-tetanus sera was used to treat soldiers with wound infections reduced mortality by x30.
- Post exposure protection in rabies- incubation is 30 days so can build immunity through vaccination before infection takes hold. Few prophylaxis vaccines available.
- Pooled human immune sera (passive) with high antibody titre against varicella-zoster virus (chicken pox) in vulnerable (neonates).
- Hypogammaglobulinemia: keep infection free with pooled normal human IgG.
Describe the immune response to an antigen
On image
Describe the general principles of vaccines
- Induce correct type of response (antibodies needed for polio, cell mediated for tuberculosis).
- Induce response in right place- mucosal- secretory IgA (flu/polio), systematic (yellow fever).
- Parenteral vaccines give poor mucosal immunity.
- Oral vaccines processed by MALT so good IgA.
- Duration of protection- short-term (travel)- antibody is sufficient, long-term- memory is essential.
- Boosters- natural (seasonal epidemics, carriage) or vaccines.
- Type of infection- long incubation time (systematic- measles) or short incubation time (surface- cholera).
- Difficult to induce long-lasting immunity at mucosal surfaces.
- Age of vaccination- maternal antibodies in neonate sIgA in milk lasts 6 months.
- Problem for live attenuated vaccines (e.g. MMR). Virus is neutralised by maternal antibody so no acquired protection .
- Vaccinate after 9 months but many babies already infected by then in endemic areas.
Describe the nature of antigens
Can serology be used to differentiate between antigens?
- Monotypic (only get once)/polytypic (can get multiple times)- antigen variation and genetic diversity. E.g. measles (monotypic) , flu and gonorrhoea (polytypic).
- Most antigens are immunogenic but not immune-protective as they can’t predict.
- Serology can differentiate exposure from vaccination. E.g. Hep B- viral surface antigen.
How can bacterial toxins be used as vaccines?
Inactivation with formaldehyde to form toxoid (antigenic and non-toxic).
Initiates antibody production and immunity with no tissue damage or disease.
What are capsular polysaccharides
Poor antigens as short term memory, no T cell immunity, less immunogenic in children under 3, poor IgG2 responses, which would promote opsonisation and major recognition of polysaccharides, also B cells less mature.
Enhance immunogenicity by protein conjugation i.e, toxoids + outer membrane proteins to get long-lasting immunity and response in children. E.g. MenC/Hib vac.
How does conjugation work?
Link polysaccharide antigen to protein carrier that the infant immune system already recognises to provoke an immune response.
Polysaccharide binds BCR and won’t produce a lot of antibody- poor memory in children.
Once conjugated, b cell will activate T cell which will in turn activate B cell through CD4 to increase antibody count against antigen as it is also being recognised by the B cell.
What are Vaccine Adjuvants?
What 3 things do they do?
- Chemicals or lipid structures that enhance immune response using vaccine components (e.g. aluminium salts and lipids- trap antibody’s in vaccine so not cleared as well/quickly so it stays in circulation longer).
- Without, immune response is much lower and not well maintained.
- Enhance immune response to antigen.
- Promote uptake and antigen presentation.
- Stimulate correct cytokine profiles.
