3 - Vaccines Flashcards
Vaccine side effects
- Inflammation and anaphylactic reactions
- Contaminates in vaccine preparation (ex: egg proteins in flu vaccine; mercury containing preservatives)
- Infection
- Improperly inactivated vaccine preparations
- Use of a live-attenuated vaccine in immune-deficient px
- Neurological and autoimmune reactions
- Caused by rare antigen cross reactions or perturbation of immuno-regulatory circuits
Autism and vaccines
Has been hypothesized that autism is induced by heavy metal poisoning associated w/ vaccination (thimerosal)
Vaccine immunology – innate immunity
- Comprises the cells and mechanisms that defend the host from infection by other organisms
- Cells of innate system recognize and respond to pathogens in a generic way
- Doesn’t provide long-lasting immunity to the host
- Innate immune systems provide immediate defence against infection
Vaccine immunology – adaptive immunity
- Composed of highly specialized, systemic cells and processes that eliminate pathogens or prevent their growth
- Creates immunological memory after initial response to a specific pathogen, and leads to an enhanced response to subsequent encounters w/ that pathogen
- Process of acquired immunity is the basis of vaccination
- Includes humoral immunity and cell-mediated immunity
Vaccine immunology
- Vaccines protect by inducing effector mechanism (both cells and molecules)
- Different components of vaccines induce different effector mechanism
- Capsular polysaccharides elicit B-cell response as T-independent manner
- Conjugation of bacterial polysaccharides to a protein carrier provides peptide antigens, which recruit antigen-specific CD4+ Tfh cells (kind of T-helper cell) as a T-dependent antibody response
- Protein antigens such as live attenuated vaccines generate CD8+ cytotoxic T cells
Effector mechanisms triggered by vaccine – antibody functions
- Prevent and reduce infections by clearing extracellular pathogens through:
- Binding to the enzymatic active sites of toxins or preventing their diffusion
- Neutralizing viral replication by preventing viral binding and entry into cells
- Enhancing extracellular bacteria clearance by macrophages and neutrophils
- Activating the complement cascade
Effector mechanisms triggered by vaccine – CD8+ T cells function
- Don’t prevent infection, but reduce, control, and clear intracellular pathogens by:
- Directly killing infected cells by release of perforin, granzyme, etc.
- Indirectly killing infected cells through antimicrobial cytokine release
Effector mechanisms triggered by vaccine – CD4+ T cells function
- Don’t prevent infection but participate in reduction, control, and clearance of extracellular and intracellular pathogens by the homing and cytokine production capacities
- Main subsets include:
- Follicular T-helper cells (Tfh) producing mainly interleukin (IL) 21 and providing B-cell help
- T-helper 1 (Th1) effector cells producing interferon gamma, tumour necrosis factor alpha, and IL-2, and mainly involved in protection against intracellular pathogens (viruses)
- Th2 effector cells producing IL-4, IL-5, IL-13 and responding to extracellular pathogens (bacteria)
- Th17 effector cells producing IL-17, IL-22, IL-26, and contributing mucosal defence (streptococcus pneumoniae)
Initiation of a vaccine response
- Pathogen-associated pattern contained in vaccine antigens attract dendritic cells, monocytes, and neutrophils that control throughout the body
- Stimulation of sufficient “danger signals” by the vaccine antigens/adjuvants activate monocyte and dendritic cells
- Activation changes their surface receptor and induces migration along lymphatic vessels to the draining lymph nodes
- In the lymph nodes, T and B lymphocytes are activated
Types of vaccines
- Killed pathogen – heat or formalin killed pathogen (ex: Salk polio vaccine)
- Live-attenuated – selection of less or non-pathogenic variants (ex: Sabin polio vaccine)
- Subunit vaccine – purified or genetically engineered structural component of a pathogen (ex: hep B vaccine)
- Conjugate vaccines – combination of multiple components to increase immunogenicity or memory induction
- Secreted or extracted bacterial products – toxoids or cell wall polysaccharides
- Toxoids are toxins inactivated by chemical treatment or induced mutation to be immunogenic but not pathogenic toxins
Features of effective vaccines
- Safe – vaccine must not cause illness or death itself
- Protective – must protect against illness resulting from exposure to live pathogen
- Gives sustained protection – protection against illness must last for several years or lifelong
- Induces neutralizing antibody – some pathogens (ex: poliovirus) infect cells that cannot be replaced (ex: neurons); neutralizing antibodies are essential to prevent infection of such cells
- Induces protective T cells – some pathogens are more effectively dealt w/ by cell-mediated responses particularly intracellular pathogens
- Practical considerations – low cost per dose, biological stability, ease of administration, few side effects
Composition of incomplete Freund’s adjuvant
Oil-in-water emulsion
Composition of complete Freund’s adjuvant
Oil-in-water emulsion w/ dead mycobacteria
Composition of Freund’s adjuvant w/ MDP
Oil-in-water emulsion w/ mutamyl dipeptide (MDP) – a constituent of mycobacteria
Composition of alum (aluminum hydroxide)
Aluminum hydroxide gel
Composition of alum + bordetella pertussis
Aluminum hydroxide gel w/ killed B pertussis
Composition of immune stimulatory complexes (ISCOMs)
Matrix of Quil A (saponin adjuvant) containing viral proteins
MOA of incomplete Freund’s adjuvant
Delayed release of Ag, enhanced uptake by macrophages
MOA of complete Freund’s adjuvant
Delayed release of Ag, enhanced uptake by macrophages, induction of co-stimulators in macrophages
MOA of Freund’s adjuvant w/ MDP
Similar to complete Freund’s adjuvant
MOA of aluminum hydroxide
Delayed release of Ag, enhanced macrophage uptake
MOA of alum + bordetella pertussis
Delayed release of Ag, enhanced uptake by macrophages, induction of co-stimulators
MOA of immune stimulatory complexes (ISCOMs)
Delivers Ag to cytosol, allow induction of cytotoxic T-cells
Various aspects of vaccine development
- Inactive or killed vaccine – vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed using a method such as heat or formaldehyde
- Live or attenuated vaccine – vaccine uses pathogens that are still active but are almost attenuated or weakened
How to generate attenuated vaccines
- Viruses may be attenuated via passage of the virus through a foreign host, such as:
- Tissue culture
- Embryonated eggs
- Live animals
- Isolate virus in human cells -> infect non-human cells -> virus mutates to grow well in non-human cells -> attenuated virus no longer grows well in human cells
What are conjugate vaccines? What is the difference between this and a free polysaccharide?
- Conjugate vaccines – created by covalently attaching a poor Ag to a strong Ag to elicit a stronger immunological response to the poor Ag
- In most cases, the poor Ag is a polysaccharide that is attached to a strong protein Ag
- However, peptide/protein and protein/protein conjugates have also been developed
- Free polysaccharide = short duration of Ab response, no memory, no affinity maturation, no response in young infants (< 18 months)
- Conjugate = long duration of Ab response, memory, affinity maturation, protective response in young infants (> 2 months)
Follicular T-helper cells
- Unique helper T cell population
- Have high Ag binding potential
- Adjuvants can affect the quantity and quality of Tfh cells
Define toxoid and DNA vaccine
- Toxoid: inactivated part of virus or bacteria, similar process to production of inactivated or killed vaccine
- DNA vaccine: uses recombinant DNA technology to introduce gene of Ag into DNA expression vector, and then introduce recombinant DNA expression vector into human or cells
What is thimerosal? What is its function?
- Thimerosal is a mercury containing compound used as a preservative in DTP, MMR, and other vaccines
- Thimerosal contains ethylmercury, which prevents growth of bacteria in vaccines and can be eliminated from the body easily
