6 - Vaccines Flashcards
Describe the B cell response to viruses?
B cells as APCs (rare), and are producers of antiviral antibodies that fix complement and make neutralizing antibodies.
This antibody response is sufficient to control very few viruses (influenza, west nile, hepatitis A and B viruses) but is mostly insufficient in controlling virus infection.
What is the T cell response to virus infection?
Required for clearance when B response is not enough (majority of viruses)
- CD8 cells required for clearance during acute infection
- CD4 cells help B cells and CD8 T cells, including making long-term CD8 T memory
What are the goals of immunization against viral disease?
To prevent infection of accelerate clearance of the virus while minimizing symptoms/disease.
Most vaccines still allow the disease, but they minimize the response and accelerate clearance.
Describe characteristics of an “ideal pathogen” for which a vaccine can be made?
- Limited # or serotypes or protective antigens
- Limited mutagenesis of protective antigens
- Infection is acute and cleared from vast majority of immunocompetent pts
- Natural immunity to infection is sterilizing (virus is cleared and reinfection with the same pathogen is prevented).
What pathogens fit the characteristics of an “ideal pathogen”?
Hep A and B Measles Poliovirus Rabies Smallpox
What are characteristics of pathogens that can or have been eradicated?
Have minimal is any mutation of antigens recognized by the immune system
Have no animal reservoir
Immunization of the vast majority of pop can be achieved (cheap and effective)
How was the smallpox vaccine developed?
Edward jenner used cowpox inoculation to show protective immunity against smallpox
Using his approach, smallpox was eradicated in 1980
What is immunotherapy and how does it work? What type of infections does this work for?
Applies to chronic infections not cleared from the host (or cleared very slowly).
Stimulates the ability of the immune system to fight an infection.
What is an example of immunotherapy that has proven to be successful?
Varicella-Zoster Vaccine (aka shingles vaccine).
VZV can reactivate from latency later in life and cause skin lesions and postherpetic neuralgia. Shingles vaccine is a stronger chicken pox vaccine given to pts over 50 to boost their immune response against VZV.
What are the types of immunization?
Passive: immune system does have to work
Active: inactive, live, or DNA pathogen introduction that makes your system work
What is passive immunization? What are examples?
Transfer of antibodies - immune response produced by another host.
Examples of transferred antibodies:
- Human Ig
- Recombinant human monoclonal antibodies
- Maternal antibodies passively immunize infants for first 9 mo of life
What is active immunization? What are the three main types of active immunization?
Admin of the antigen that makes the host generate an immune response against the antigen.
3 types: live, inactivated, and rDNA-based
Describe live vaccination and examples?
Amin of a fully infectious agent capable of some replication.
Polio, measles, mumps, rubella, VZV, flu, and smallpox.
What are advantages of a live vaccination?
Humoral and T cell mediated immunity, usually no adjuvant needed.
Long lived response and mucosal antibodies.
Generally cheaper to make.
*immune system may be able to recognize activities of live microbe to improve response
(emerging concept)
What are the disadvantages to live vaccination?
Expensive to store, more symptomatic, may cause disease in immunocomp.
Can be transmitted to immunocomp, revertance to virulent, potential to carry other life viruses on board within vaccine.
What was the action of the live attenuated polio vaccine created by Sabin? What are the advantages and disadvantages?
Given orally and replicates in intestines.
Good: inexpensive, easy to give, makes systemic and mucosal antibodies.
Bad: can mutate to more virulent strain and less reliable in tropical climates.
What are four ways to design a live vaccine for a virus?
- Isolation of naturally attenuated viral mutant - passage of virus in unrelated host sometimes generates a mutant with decreased virulence.
- Identification of virus that naturally infects different species
- Temperature sensitivity - passage of virus in culture under reduced temp and selection of mutants that no longer effectively replicate at body temp
- Direct mutagenesis
What is an inactivated vaccine?
Admin of a viral antigen that elicits immune response but cannot result in the generation of infectious virus.
What are the advantages of using an inactivated in vaccine?
Easy to store, generally safer than live vaccination, and fewer symptoms of vaccination as compared to live vaccines.
What are the disadvantages of using an inactivated in vaccine?
More expensive to produce, requires adjuvant, generally only humoral immunity induced (no IgA), and requires more booster shots and sometimes larger doses.
Describe the advantages and disadvantages of the inactivated polio vaccine made by Salk?
Good: cannot undergo mutation to increase virulence, safe for immunocompromised.
Bad: no gut immunity, requires parenteral admin, expensive, requires multiple immunizations (boosters), and must ensure antigenic potency and inactivation.
What are the ways to design an inactivated vaccine?
Killed inactivated: infectious virus mixed with inactivating chemical - flu shot
Subunit vaccine: purified recomb. viral proteins that cause protective immune response (usually envelope or capsid) - Hep B, newer flu
Virus-like particles: type of subunit vaccine. Some recomb. proteins will self-assemble into empty viral particle - HPV vaccine
What is an adjuvant? What adjuvants are used in inactivated vaccines?
A “danger” signal for the immune system that makes antigen presenting cells more potent at stimulating immune responses.
In US - alum is oldest/most popular, but not great
Newer have MF59 (emulsified squalene) and monophosphoryl lipid A (MPL).
What is herd immunity?
Resistance to the spread of a contagious disease within a population that results if a sufficiently high proportion of individuals are immune to the disease, especially through vaccination.
What is the threshold level needed for herd immunity to occur?
~90% vaccination rate appears to be the threshold needed for herd immunity to be effective and prevent the spread of infection.
How are infants protected for virus infections?
9 mo from maternal antibodies, which can attenuate immunization to the same pathogen - higher doses and more boosts are needed.
What is the immune response in the first 12 months of life in infants?
It’s immature: CD8 cell response is attenuated and humoral is the default pathway.
Infant antibodies are freq not hypermutated (decreased affinity) and have limited in isotype switching.
Describe the immune system in the elderly?
Decreased expansion of T and B cells in response to antigen.
High proportions of CMV-specific T cells attenuates the development of T cell responses against other pathogens.
Decreased cytokine production and waning of immune competence requires more aggressive prevention of infectious disease.
