14 - Vaccination Flashcards
Variolation
Pus taken from a smallpox blister and introduced into skin of an uninfected person to confer protection
Who discovered vaccination
Edward Jenner
Discovery of vaccination
Inoculation with cowpox protects against smallpox (closely related)
First human viral disease to be eradicated by vaccination
Smallpox (caused by infection with variola virus) via protective immunity induced by closely related virus (vaccinia virus)
Herd immunity
- Occurs when a large portion of a community becomes immune to a disease.
- The spread of disease from person to person therefore becomes unlikely, protecting susceptible individuals who cannot be vaccinated
Passive immunity
- Administration of antiserum containing preformed antibodies
- Immediate protection against recent infection or ongoing disease
Limitations of passive immunity
Can trigger hypersensitivity, antibodies are degraded very quickly
Active immunity
- Protection induced by person’s own immune system with specificity and memory
- Both humoral and cell mediated
- Can last decades
Types of vaccines
Inactivated, subunit, killed
Passive natural immunity
Antibodies acquired through breast milk or placenta
Passive artificial immunity
Immunity gained through antibodies harvested from another person or animal
Active natural immunity
Immunity gained through illness and recovery
Active artificial immunity
immunity acquired through vaccine
Rabies
- Zoonotic viral disease spread to humans via bite of infected animal
- Virus travels along nerves to reach CNS
- Delay between infection and arrival in CNS means post-exposure prophylaxis can prevent disease
- Most people with symptomatic rabies do not survive
Rabies vaccine
Inactivated vaccine (killed virus), or rabies immunoglobulin are offered, depending on exposure or degree of risk
Live attenuated viral vaccines
- Have modified genomes and are less virulent than wild type viruses
- Antigens are similar enough to WT to induce immune response that protects against WT
- More potent than killed/inactivated/non replicative antigens as they infect target cells and induce a broad range of effect immune responses (including CD8+ T cells)
Method for deriving live attenuated vaccines
- Pathogenic virus is isolated from a patient and grown in human cultured cells
- The cultured virus is used to infect monkey cells
- The virus acquires many mutations that allow it to grow well in monkey cells
- Virus no longer grows well in human cells
Why are live attenuated replicating virus vaccines best immunogen
Because both T cell and B cells responses are induced
What response is best for immunisation
Not just antibodies, also CD8+ T cell specific response
Yellow fever vaccine
- Derived by passage thorugh mice and other lab animals
- 48 nucleotide substitutions (of ~11,000 nt) of which 22 are non-synonymous, scattered throughout genome
- Induces neutralising antibodies and T cell responses
Polio sabin attenuated vaccine
- Grows in epithelial cells
- Does not grow in nerves (no paralysis)
- Local gut immunity (IgA), important as virus replicates in gut
- 1 in 4,000,000 vaccine infections
Polio salk killed vaccine
- Formaldehyde fixed
- No reversion
- No gut immunity
- Cannot wipe out wild type virus
Subunit vaccine advantages
- Prepared from components of virus (proteins). May self aggregate to produce virus like particles
- Recombinant DNA technology
- No viral genomes or infectious virus
Subunit vaccine disadvantages
- Expensive
- Injected
- Poor antigenicity
HPV vaccine
- HPV vaccine is a non infectious virus like particle
- One of most successful vaccine
- Quadrivalent vaccine includes HPV types 6, 11, 16 and 18
Polysaccharide vaccines
- Induce short lived antibody producing plasma cells by cross linking the BCR
- Affinity maturation of the antibody response and the induction of memory B cells do not occur
Protein polysaccharide conjugate vaccines
- Can engage T cells that recognize the carrier protein, as well as B cells that recognize the polysaccharide.
- T cells provide help to B cells, leading to affinity maturation and the production of both plasma cells and memory B cells.
Adjuvant
Substance added to vaccine to increase body’s immune response to vaccine
How do adjuvants work
- Act as antigen depot, releasing it slowly
- Inducing an inflammatory response that enhances the host immune response to the vaccine antigen
Is T cell vaccination predicted to prevent infection
No, but is predicted to control the viral load until escape mutants arise
Features of effective vaccines
- Safe
- Protective
- Gives sustained protection
- Induces neutralising antibody
- Induces protective T cells
- Practical considerations
