FMS Week 10: Vaccines Flashcards
Adaptive immunity and the primary infection
What are vaccines?
Vaccines are harmless agents that elicit adaptive immune responses
Consequences of immunization
4 listed
- circulating Antibody in serum (ideally high-affinity IgG)
- Increased frequency of pathogen-specific B and T cells (memory cells)
- Rapid response to infection
- these immune responses prevent or modify disease
Most Vaccines do not prevent infection but…
some do!
Herd Immunity
Pathogens are unable to spread if they cannot infect people
The first vaccine was
Smallpox
Critical issues in Vaccine Development
3 Listed
Most modern vaccines against bacteria target …
Capsular Polysaccharides
Typical Extracellular Bacteria Vaccine targets
3 Listed
- Capsular Polysaccharides
- Bacterial toxins
- induce neutralizing antibodies
Appropriate targets of Intracellular Bacteria
2 Listed
- CTL responses are probably the most important (antibodies may also have value)
- There are no particularly effective vaccines against intracellular bacteria that are currently clinically approved
Effector mechanism likely for Tuberculosis?
T cell Vaccines
Factors that influence the immune response as it pertains to vaccines
5 Listed
- Type of Antigen (structure, protein vs carbohydrate)
- Dose, route of administration (e.g. intramuscular, subcutaneous, Mucosal, etc.)
- Age (newborns, infants/children, adolescents/adults, elderly)
- Adjuvants
- State of the host: e.g. underlying immune deficiency (e.g. splenectomy, HIV infection, congenital immune deficiency, chemotherapy)
Adjuvant definition
Adjuvants are agents that enhance the immunity induced by vaccines
Adjuvant functions
3 Listed
- can enhance translocation of antigens to lymphoid tissues
- Provide physical protection to antigens, allowing a more prolonged exposure to the immune system
- Often provoke local immune reactions at the site of immunization, usually through interactions with innate immune receptors such as TLRs
Common Adjuvants
4 Listed
- Alum
- Mineral Oil
- Squalene
- TLR agonists (MPL & CpG)
Main Classes of Vaccines
6 Listed
- Live Attenuated
- Inactivated
- Subunit
- Conjugate
- Virus-like particles
- DNA
Classical Vaccine Strategy classes of vaccines
3 listed
- Live Attenuated
- Inactivated
- Subunit
Classes of Vaccines: Recombinant DNA Technology
4 Listed
- Subunit
- Conjugate
- Virus-Like Particles
- DNA
Safety of the various vaccine types
Most Safe
- DNA
- Recombinant proteins and VLPs
- Isolated pathogen components
- Inactivated
- Live Attenuated
Least Safe
Immunogenicity of the various vaccine types
Most Immunogenic
- Live attenuated
- Inactivated and VLPs
- Isolated pathogen components
- Recombinant proteins
- DNA
Least Immunogenic
Live Attenuated Vaccines definition
Live pathogens that replicate in the host but do not cause disease because the pathogen has been mutated to a non-pathogenic form
Live Attenuated Vaccines: Methods of Attenuation
6 listed
- Repeated passage in a different species
- Repeated passage in cell lines
- Repeated passage in cold
- Genetic reassortment with attenuated genes
- Deletion or mutation of genetic sequences
- Use of a naturally occurring non-pathogenic relative
Consequences of Attenuation
4 Listed
- Tropism
- Gene expression
- Immunogenicity
- Ability to replicate
Advantages of Live Attenuated Vaccines
4 Listed
- Highly immunogenic and stimulates a broad immune response (innate and adaptive)
- All antigens are expressed (multiple targets)
- Usually effective with a single dose
- Often inexpensive to manufacture
Disadvantages of Live Attenuated Vaccines
4 Listed
- Can revert back to pathogenic form
- Requires a system to grow the virus
- Potential for contamination
- Can be dangerous in immunodeficient or pregnant individuals
Inactivated Whole Pathogen Vaccines Description
Preparations of normal, infectious pathogen that have been inactivated, usually by treatment with a clinical agent
Advantages of Inactivated Vaccines
2 Listed
- Reversion not an issue
- Multiple Antigens are present
Disadvantages of Inactivated Vaccines
6 Listed
- Risk of incomplete inactivation
- Requires a system to grow the virus
- Manufacture requires handling of large volumes of virulent pathogen
- Manufacture often expensive
- Inactivation may alter immunogenicity
- Requires Boosting
Comparisons of immune responses to live and killed vaccine
Subunit Vaccine Description
4 listed
Consists of purified components derived from the pathogen such as
Subunit Purified Components Examples
3 Listed
- Toxins (Tetanus, Diptheria, Pertussis)
- Polysaccharide derived from bacterial capsule (pneumococcus, Meningococcus)
- Viral Surface antigens (Hepatitis B Surface Antigen)
Advantages of Subunit Vaccines
1 Listed
- Can induce specific immune responses against molecules involved in virulence/pathogenesis
Disadvantages of Subunit Vaccines
2 Listed
- Often poorly immunogenic without adjuvants
- Polysaccharide antigens elicit T-independent responses
T-Cell-independent Immune Responses of Polysaccharide Vaccines
Conjugate Vaccines Description
2 listed
Consist of purified component(s) of a pathogen linked to a highly immunogenic carrier (such as inactivated bacterial toxins)
&
Allows for a T-dependent antibody response
T-Cell-Dependent Immune Response to Protein or Protein-conjugate Vaccines
Virus-like Particle Vaccines Description
2 Listed
- Consist of the viral structural proteins that when overexpressed, spontaneously self-assemble into particles that are indistinguishable from infectious virus
- VLPs do not contain viral nucleic acid and are therefore, non-infectious
Advantages of Virus-like Particle Vaccines
4 Listed
- Excellent safety profile
- Does not rely on the ability to grow pathogen
- Highly immunogenic due to the repetitive structure
- Inside of particle can be modified with adjuvants
Disadvantages of Virus-like Particle Vaccines
3 Listed
- May require multiple doses (recent data says maybe not)
- Induces a limited immune response (to surface antigens)
- Can be expensive to manufacture
DNA Vaccines Description
3 Listed
- Injection of DNA coding for the target molecule. The gene can be introduced using a viral vector or can be injected as naked DNA. Once the DNA enters the cell, the target antigen is expressed at high levels
- Secreted antigens can elicit antibodies
- Antigens delivered to APCs can elicit T cell responses
Advantages of DNA Vaccines
3 Listed
- Inexpensive to manufacture
- Vaccines are often highly stable
- quick development time
Disadvantages of DNA Vaccines
4 Listed
- Effectiveness is unclear
- It May be more effective in generated cell-mediated immune responses (for therapeutic vaccines)
- Safety unclear
- Likely require multiple doses and multiple delivery platforms
Barriers to vaccine development
4 Listed
- Target Identification
- Immunogenicity (magnitude of Response)
- Safety issues (especially with new technologies)
- Antigenic Variation (RNA viruses (such as HIV, Influenza, Hepatitis C Virus) Certain bacteria and protozoa)
Emerging Trends in Vaccines
4 Listed
- Novel Delivery Systems
- Novel Adjuvants
- Emerging Infectious Diseases
- Non-traditional Vaccine Targets
Novel Delivery Systems Examples
4 Listed
- Mucosal Delivery
- Skin patches
- Microneedles
- Aerosol
Novel Adjuvants Examples
3 Listed
- Activators of innate immunity
- Toll-like Receptors (CpG oligonucleotides, others)
- Targeting of specific cell types (B cells, Mucosal cells)
Trends in Vaccines: Emerging Infectious Diseases description
Rapid production of vaccines to face emerging threats
Non-traditional Vaccine Targets Examples
3 listed
- Self-molecules involved in disease processes
- Allergens
- Substances of abuse (Nicotine, Cocaine)
Harmonized Schedules for Vaccination
4 Listed
- Provided by the American Committee on Immunization Practice (ACIP) under the National Immunization Program (CDC)
- Schedules of primary series and booster injections for children and adults
- ACIP general recommendations and harmonized schedules define acceptable variation in dosing, vaccine intervals, and age of immunization
- Updated every year
Alleged or Disproved Vaccine Adverse Effects
4 Listed
- Causation or relapse of Multiple Sclerosis; Hep B Vaccines
- Causation of juvenile diabetes; Haemophilus Vaccines
- Causation of convulsive disorders or chronic encephalopathy; whole cell DPT
- Causation of autism; Measles Vaccine; Thimerosal (Ethyl mercury)
Immediate Vaccine Reactions time frame
Within 24 hours
Delayed Vaccine Reactions time frame
Within 14-28 days
Generalized systemic reactions of Vaccines
5 Listed
- Fever
- Arthralgia
- Headache
- Fatigue
- Generalized Rash
Arthralgia AKA
Joint pain
Local Reactions of Vaccines
3 Listed
- Swelling
- Pain
- Erythema
Allergic Vaccine Reactions
4 Listed
- Anaphylaxis
- Generalized urticaria (hives)
- Dizziness
- Syncope (fainting)
Likelihood of Allergic Vaccine Reactions
- Rare events & risk is minimized by screening (do you have an allergy to eggs)
Transient Thrombocytopenia Description & Vaccine Reaction
2 listed
- Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes, also known as platelets, in the blood
- e.g. Measles; immune-mediated
Rare Vaccine Reaction Associations
2 Listed
- Guillain-Barre Syndrome
- Post-vaccine encephalitis
VAERS AKA
Vaccine Adverse Effects Reporting System (VAERS)
Vaccine Preventable Diseases Examples
15 Listed
