L5 vaccination

Variolation

inject patients with active small pox

• disease that have been globally eliminated

• disease poised for global elimination

• small pox (1980)

• rinderpest (2011)

poised (one reservoir, one source — human)

• polio

• measles

• guinea worm

Natural adaptive immunity

acquired as part of normal life experience, NO MEDICAL INTERVENTION

type:

• natural passive immunity

• natural active immunity

artificial adaptive immunity

acquired through a medical procedure (i.e. vaccine)

type:

• artificial passive immunity

• artificial active immunity

natural passive immunity

transfer of preformed antibodies from mother to fetus (placental → IgG) or newborn child (milk)

natural active immunity

development of immunity by naturally contracting the disease

artificial passive immunity

• definition

• advantage

• disadvantage

• transfer of preformed antibodies from a vaccinated individual (or animal) to a recipient

• used in immunocompromised individuals or cases in which immediate effects are required (snake bites, tetanus)

advantage

• simple process, act immediately

disadvantage

• short term (2-3 months)

• does not create memory

• consists only a transferred element (Ab) with SINGLE moa

• no evolution of immunity to greater strength and specificity

artificial active immunity

• definition

• advantage

• disadvantage

• inject recipient with antigen (s) that stimulate production of antibodies or reactive cells → create memories, takes time, and is lasting

advantage

• long term effects, elicit memory

• stimulate multi-component response (ab and cell mediated immunity

• evolution of response toward greater strength and specificity

disadvantage

• more complex process

• takes time to develop immunity (cuz we are stimulating 1˚ response)

Killed or inactivated vaccines

• cultivate desired strain, treat it with formalin or other agent that kills the strain but does not destroy its antigenicity

• often require a larger dose and more booster to be effective

• ex. SALT polio

Live attenuated cells or viruses

• use process that substantially lessen or negates the virulence of viruses or bacteria, but alive

• usually pass virus to cell they not use to

  • ex. Sabin vaccine - polio thru monkey - once adapted to monkey → don’t do well in human

advantage and disadvantage of live preparation of live attenuated vaccine

Think sabin polio vaccine

• Advantages of live preparations are:

–Can multiply and produce limited infection (but not disease) like the natural pathogen

–They often confer greater and longer-lasting protection

–Usually require fewer doses and boosters

• Disadvantages of live preparations include:

–Sometimes require special storage

–Can potentially be transmitted to other people

–Can conceivably mutate back to virulent strain

Acellular or subcellular vaccine (subunit - if a virus)

• antigens stimulate imunity but no pathogen is present

• exact antigenic determinants can be used when known:

  • capsules - pneumococcus, meningococcus

  • surface protein - anthrax, hep B

  • exotoxin - diphtheria, tetanus

Genetically engineered vaccines

• insert genes for pathogen’s antigen into plasmid vector → clone them in an appropriate host → stimulate the clone host to synthesize and secrrete a protein product (antigen) → harvest and purify the protein.

ex. hep B

Genetic engineered vaccine: “trojan horse” vaccine

• genetic material from a pathogen is inserted into a live carrier nonpathogen → recombinant expresses the foreign gene

• currently in experimental stage

Genetically engineered vaccine: DNA vaccines

• naked DNA or microbial DNA inserted into plasmid vector

• human cells will pick up the DNA plasmid and express the microbial DNA as protein → cause B and T  cells to respond, be sensitized, form memory cell

• currently in experimental stage

Genetically Engineered vaccines: RNA vaccines

• same idea as DNA, but use RNA to induce production of desired antigen in host cells

• COVID

Advantages and disadvantages of RNA vaccine

Advantages

• Directly translated in cytoplasm -- no need for nuclear uptake, no alteration of host genome

• Modified nucleoside forms available that avoid degradation

• Can be engineered for optimal translation in various organisms/tissues

• Standardized and scalable methods for synthesis, manufacturing and delivery

Disadvantages

• Can elicit cellular antiviral response (interferon) that will destroy the vaccine RNA

• Can lead to inflammatory reactions and, potentially, immune hypersensitivities

Thimerosal (mercury) in vaccines

• mercury-based preservative once added to some vaccines and injectables.

• safe and effective, with no link to autism or other diseases

• It was removed from most vaccines over 25 years ago out of caution,

• kept in some influenza vaccines to allow safe use of multidose vials and lower cost during mass immunizations.

• never used in MMR vaccines, and the CDC’s Advisory Committee has recently voted to remove it from all influenza vaccines as well.

Aluminum in vaccine

False claim: ingredient in vaccines responsible for inducing allergies, depression and autism

• adjuvant to enhance the immune response → allowing lower doses and fewer boosters, especially in killed or subunit vaccines.

• It is not used in live vaccines like MMR.

• very well studied, with an excellent safety record backed by billions of doses.

• Infants up to 6 months in the U.S. receive about 4 mg of aluminum from vaccines.
  In comparison: much lower than daily intake of aluminum.

Guillan-Barre syndrome

• complication of several vaccine, especially influenza

• 1/100,000 vaccines

• neurological condition - destruction of peripheral neuronal myelin sheath → weakness and sensory loss

• due to autoimmune reaction elicited by viral proeins

• most patient recover but some get chronic GBS and some die