Semester 2: Vaccines and Vaccine Immunology Flashcards
What is immunization?
The process of producing a long-term, adaptive immunological response to a pathogen
What are the conditions that a vaccine should fulfill.
Prevent the establishment and spread of a given infection
Produce antibodies against one or more epitopes of the pathogen
Provide lifelong protection (memory response)
Be immunogenic against the desired antigen
Be safe
What is passive immunity with regards to vaccine?
The transfer of active immune mediators to a host Typically antibodies Maternal transfer Artificial transfer Provides protection against antigen Does not provide memory
What is active immunity with regards to vaccines?
The production of active immune mediators within a host
Innate adaptive (humoral and cellular)
Provides protection against antigen
Provides immune memory
What is innate immunity?
Antigen non-specific
Involves recognition of PAMPs and DAMPs
Produces antimicrobial cytokines/chemokines, leads to inflammation, complement activation and clearing
Provides limited immunological memory
What is adaptive immunity?
Antigen-specific
involves recognition of antigenic peptides following antigen presentation by APCs
Produces a cellular response (T cell, cytotoxic)
Humoral response (B-cell, antibody)
Immunological memory and sterilizing immunity
When was the first vaccine administered?
1796 to a 6 year old boy for smallpox, inoculated with scrapings of cowpox lesions
What characteristics does an ideal vaccine have?
Produces a lifelong memory response to infection that is sufficient to prevent disease following subsequent exposure to a given pathogen
Which immune processes should be taking place when a person is vaccinated?
Both innate and adaptive
Innate influences the nature of the adaptive response
Which immune response is crucial to efficacy?
Adaptive response
What are the four vaccine types?
Live attenuated
Killed/inactivated
Subunit
Toxoids
What are live attenuated vaccines?
Live/viable whole bacteria, virus etc
Often replication-deficient
May be strains of pathogen that do not cause disease in host (smallpox vaccine)
Grown in vitro
What are the advantages of live attenuated vaccines?
Highly immunogenic
Best mimics exposure to the pathogen
Induces a response against multiple components of the pathogen
What are the disadvantages of live attenuated vaccines?
Highly immunogenic
May cause mild illness
Difficult to develop against highly mutagenic pathogens
What are killed/inactivated vaccines?
Non-living/non-viable whole bacteria, virus etc
Do not replicate, do not elicit de novo bacterial/viral gene expression
Inactivation by heat, irradiation, chemical inactivation
What are the advantages of killed/inactivated vaccines?
Vaccine components cannot replicate
Contains multiple epitopes/antigens
What are the disadvantages of killed/inactivated vaccines?
Relatively less immunogenic than live attenuated vaccines
May cause mild illness
Chemical inactivation compounds may elicit adverse reactions (Formaldehyde)
What are subunit vaccines?
Contain one or more components of a pathogen
Do not replicate, do not elicit de novo bacterial/viral gene expression
May be delivered in a recombination vector
What are the advantages to subunit vaccines?
Vaccine components do not replicate
Higher safety profile
What are the disadvantages to subunit vaccines?
Relatively less immunogenic than live attenuated or inactivated vaccines
Contains limited epitopes/antigens
Does not effectively mimic the natural exposure of the host to pathogen
What are toxoid vaccines?
Contains a modified or inactivated toxic component of a pathogen
I.e. diptheria toxoid, tetanus toxoid
Does not replicate, is not toxic, elicits immune response against bacterial/viral ect. toxin
What are the advantages to toxoid vaccines?
Vaccine components cannot replicate
Higher safety profile?
What are the disadvantages to toxoid vaccines?
Relatively less immunogenic than live attenuated or inactivated vaccines
Contains limited epitopes/antigens
Does not effectively mimic the natural exposure of the host to pathogen
Why are vaccines recommended to immunocompromised patients?
To reduce risk of complication in response to exposure to disease
What vaccines are CI’d in severely immunocompromised patients?
Live vaccines
What vaccine components may elicit allergic reactions?
Formaldehyde
Egg albumin
What vaccines are CI’d in pregnant patients?
Live vaccines
What would cause you consider the possibility of neurological complications in response to a vaccine?
History of Guillian-Barre syndrome (autoimmune) in response to vaccine
What vaccines are grown in chick embryos and therefore may contain egg albumin?
Influenza virus
Measles, mumps, rubella (MMR)
Rabies virus
Yellow fever virus
What preservatives are added to vaccines?
Formaldehyde
Thimersoal (mercury)
Antibiotics
Why are adjuvants/immunogens added to vaccines? What substances are added?
added to vaccines to instigate or potentiate an immune response to the vaccine epitopes
Alum, aluminum
Squalene
What is squalene?
An organic component (cholesterol precursor) produced by all plants and animals, including humans.
Higher levels of anti-squalene antibodies found in patients suffering from gulf war syndrome
What is gulf war syndrome?
Spectrum of acute and chronic illnesses observed in military following exposure to a variety of chemical weapons, depleted uranium, combat stress, and vaccines.
Fatigue, muscle weakness, myalgia, cognitive impairment, rash, diarrhea
Unclear etiology - no link to squalene
What is vaccine-associated paralytic poliomyelitis? What is the incidence rate?
Reversion of vaccine strain to a neurovirulent strain of virus (oral polio vaccine)
Incidence rate - 1:2,400,000 cases
What is a possible risk from the rotavirus vaccine?
Intussusception
1~2:100,000 infants
What are the four childhood vaccines?
Pentavalent combination (Diptheria toxoid, tetanus toxoid, acellular or whole killed pertussis, inactivated poliomyelitis, H.influenza serotype b) Pneumococcal vaccine (strep pneumoniae polysaccharides or conjugated to modified DT) Meningococcal (neisseria meningititis polysaccharides or conjugated to modified DT/TT) MMR (measles mumps rubella all live attenuated)
What are the adult vaccines?
Human papillomavirus
Poliovirus (salk killed oral poliovirus vaccine)
Influenza virus (2 A serotypes and 1 B serotype, live attenuated or killed whole)
Tetanus (toxoid vaccine, booster every 10 years)
What are the vaccinations for travel to high risk areas?
Hep A Hep B Yellow fever virus Salmonella typhi (typhoid fever) Vibrio cholera
Why do some vaccines need boosters?
Duration of protection of different vaccine formulations is highly variable. Many influences on the maintenance of memory T cell and memory B cells. Some vaccines require booster shots to re-stimulate the immune system
Some vaccines schedules requires multiple stimulations to achieve lifelong immunity (HPV, HAV, HBV)
What are current vaccines in development?
HIV vaccines
Cancer vaccines
What is the MOA of cancer vaccines?
Post exposure prophylaxis, therapeutic vaccines
Vaccine immunizes against tumor-associated antigens (TAAs)
Many clinical trials in progress
What are the emerging vaccine platforms?
DNA-based vaccines
Dendritic cell-based vaccines (stimulate with DC with antigen to achieve antigen presentation. DCs removed and then immunized via peptide/DNA/viral vector. Immunized DCs are reintroduced to the patient to stimulate immune response)
Plant based vaccines (transgenic plants to produce large-scale subunit vaccines)
CAR vaccines (Chimeric antigen receptors, stimulates T cell mediate response associated with better antitumor responses)
