Hdm Test 4, Vaccines

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active immunity vs. passive immunity

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ACTIVE immunity: the body's response to exposure to a potential pathogen (via immunization, natural infection or exposure), hopefully leading to a long-term protective response
PASSIVE immunity: created via the transfer of pre-formed antibodies to an individual (no long-term response

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definition of vaccine

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a substance designed to induce a potent and protective immune response to potential microbial pathogens by exposing the host to antigenic, but non-pathogenic material

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purpose of vaccination

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prevention of the multiplication of invading microorganisms, neutralization of their toxins
[vaccines provide the opportunity to elicit an immune response in an individual to either prevent or modify the disease process]

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types of vaccines (4)

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whole killed/inactivated organism
live, attenuated organism
purified antigen/subunit
synthetic/recombinant
(also DNA vaccines)

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factors involved in the prevention of infection (at least 5)

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innate immunity
acquired immunity (to past infections/exposures)
avoidance of exposures to pathogens
general health (e.g. nutrition)
many others...

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passive immunization -- products

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include pooled polyclonal antibody, hyper-immune antibody preparations monoclonal antibodies

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common uses of passive immunization

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situations when immediate protection is needed, when the host is unable to produce an adequate immune response, or selected situations when no safe or effective vaccine is available to provide active immunity

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active vs. passive immunization -- length of time

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passive: short lived, does not induce memory
active: hopefully leads to a long-term protective response

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animal bite management

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-- emergency evaluation, supportive care
-- wound management, prevention of bacterial infection
-- consider risk of tetanus
-- consider risk of rabies (if high risk- administration of RIG and vaccine)

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management of well 5 month old who was delivered at 27 weeks, routine visit prior to onset of typical RSV season

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currently no safe or effective vaccine for RSV; a monoclonal antibody preparation is available for monthly injection to prevent severe RSV infections

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management of 10 month old with underlying immune deficiency with decreased immunoglobulin production

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need for Ig replacement therapy

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specific situations to use passive immunization

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- against tetanus, botulism, diphtheria, snake venom
- Rho-Gam to prevent Rh- mothers (with Rh+ fetus)
- polyclonal gamma globulin (e.g. IVIg) for serious deficiencies of humoral immune system
- antibody products directed against specific viral antigens (e.g. HepA, CMV, rabies, RSV)
- various other infections and autoimmune diseases

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whole bacteria or virus vaccines -- production

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either killed (inactivated) or weakened (attenuated) prior to use as vaccine

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inactivated bacteria or virus vaccines -- production

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large numbers of virus or bacteria grown then killed (inactivated) using heat or chemical fixation

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attenuated, live vaccines -- production

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repeated passages of the organism through cell culture or through lab animals until a non-virulent organism is isolated

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inactivated bacterial vaccines -- protection (immunity)

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usually generate limited protection, short-lived
NONE part of the routine recommended vaccines in US (used some in other countries)

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inactivated viral vaccines -- protection (immunity) and examples

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may not produce as good or as long-lived protection
e.g. inactivated influenza, rabies, polio (Salk) vaccine

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attenuated, live viral vaccines -- protection (immunity)

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effective; generate long-term protection
protection/immunity may be lifelong, but booster doses are recommended for some vaccines
e.g. measles (rubeola), mumps, rubella, chickenpox, rotavirus, live oral influenxa vaccine, [also oral polio, yellow fever]

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what is the benefit of the ability of attenuated live viruses to infect cells?

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the generation of both an antibody response and a good CTL response

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attenuated bacterial vaccines -- protection (immunity)

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e.g. BCG organism for TB

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one con of attenuated vaccines

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they contain live organisms, therefore safety is a concern in certain patients (e.g. those with immune deficiency)

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management of vaccinations in a well 15 month old patient with HIV

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Routine immunizations for this age: MMR and varicella vaccines
**Administration of these vaccines to children with specific immune deficiencies or those taking immunosuppressive agents depends on the degree of immune suppression**

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toxoid vaccines

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toxins inactivated, usually by chemical modification
very effective immunogens
e.g. diphtheria, tetanus

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purified polysaccharide antigens

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not efficient at inducing long term protection (T independent)
more effective when coupled to proteins --- conjugate vaccines
e.g. H. influenza type b chemically conjugated to tetanus toxoid

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advantage to purified antigen/subunit vaccines

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very safe

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disadvantages to purified antigen/subunit vaccines

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- short shelf-life
- difficulty in producing the vaccine
- failure to stimulation CTL response since they are mostly recognized as exogenous antigens

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synthetic/recombinant antigen vaccines -- active part

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a synthesized protein/amino acid(s)
-- amino acid polymer corresponding to antigenic determinants
-- large peptide
-- entire protein

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synthetic/recombinant antigen vaccines -- technology requirements

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technology requires identification of antigenic epitopes on a particular molecule
e.g. Hep B vaccine

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advantage to synthetic/recombinant antigen vaccines

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safe

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disadvantages to synthetic/recombinant antigen vaccines

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short shelf-life, difficulty in producing the vaccine, failure to stimulate significant CTL response

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live viral vector vaccines

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-- Introduction of genes encoding microbial antigens into the genome of a non-cytopathic virus
-- Induces a strong CTL response, B cell response, and memory
-- A common viral vector is vaccinia virus; several viruses have been utilized
-- Multiple clinical trials of vaccine candidates; safety concerns

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DNA vaccines

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-- Inoculation of a plasmid containing a specific gene
-- Plasmid DNA integrates into cell genome, is expressed, inducing both T and B cell responses
-- Naked DNA is delivered into host cells in vivo

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polyvalent/combination vaccines -- examples

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*diphtheria, tetanus, and pertussis combination vaccine used for some time
*pentavalent vaccine with antigens for diphtheria, tetanus, pertussis (acellular vaccine), hepatitis B (recombinant protein), and Haemophilus influenzae b (Hib)

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advantage to polyvalent/combination vaccines

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reduction in number of injections

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polyvalent/combination vaccines -- limitations

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not all vaccines can be combined
- risk of interference with immune responses
- all comb. vaccines tested to confirm adequate immune response for each component
- many are not available world-wide

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what additional substances/components are in a vaccine?

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adjuvants
diluent
atbilizers
antibiotics
preservatives

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adjuvants -- definition, example

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substances added to vaccine to improve or stimulate the immune response

*Some substances induce severe inflammation in humans*
E.g. common adjuvant: Aluminum salts (e.g. aluminum hydroxide gel)

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diluent

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usually water or saline

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what do stabilizers do? examples

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maintain vaccine potency
e.g. MSG, albumin, phenols, gelatin, glycine

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general principles of vaccine efficacy (1 of 2)

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immunization against microorganisms that are limited to human hosts and are invariant in their surface structures is effective
e.g. smallpox

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general principles of vaccine efficacy (2 of 2)

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vaccination programs against microorganisms that have animal reservoirs and exhibit diversity in their surface structures are likely to be LESS effective
e.g. influenza

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examples of diseases for which vaccines exist

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((see pictures on PP))
smallpox, polio, diphtheria, measles, mumps

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Are additional vaccines still needed?
Why or Why Not?

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Yes!
**Many important infectious diseases still have ineffective means of prevention
**Many diseases without vaccines are the cause of significant morbidity and mortality worldwide
**Integration of communities and populations across the world
**The emergence of greater antimicrobial resistance

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benefits of immunization

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individual immunity
herd immunity (microorganism have difficulty surviving in the population)

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risks of immunization

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adverse reactions
- local reactions
- mild systemic reactions
- varied allergic reactions
ongoing concerns about vaccine safety

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who tests the safety of vaccines?

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FDA
ACIP (Advisory Committee on Immunization Practices, *part of CDC*)
state legislatures

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vaccine safety 'hot topics'

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possible role of vaccines/constituents in several disease processes:
autism (MMR)
thimerosal
other childhood disorders (SIDS, MS, autoimmune)

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Some studies have raised the possibility that the MMR vaccine or the use of the preservative thimerosal is linked to the development of autism...

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... Convincing studies and reviews have refuted this association.

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what pathogen should be considered if a patient who has had no immunizations has periorbital cellulitis?

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Haemophilus influenza type b