Antimicrobial Vaccines Flashcards
1
Q
Immunization Goals
A
- Prevent infection and/or reduce severity of disease in a given individual
-
Reduce transmission and if possible eradicate an infectious disease at the population level
- Herd immunity ⇒ possible if vaccine coverage high enough
2
Q
Protective Responses
A
- ⊗ colonization or invasion
- ⊗ growth and/or dissemination of microbes
- Promote lysis and/or phagocytosis
- Neutralize toxins
- Counter immune evasion strategies
- Facilitate pathogen recognition by immune system
3
Q
Passive Immunization
Definition
A
Transfer of human (or equine) Ig w/ high concentration of Ab for specific pathogen or toxin to non-immune individuals.
Ex. passive transfer of IgG from mother to fetus
4
Q
Therapeutic
Passive Immunization
A
-
Prevent disease in non-immune pts when high risk but not enough time for active immunization
- Ex. needle stick w/ HBV blood
-
Reduce sx of ongoing disease
- Ex. tetanus d/t would infection
- Protect immunosuppressed or immunodeficient individuals
5
Q
Passive Immunization
Pros and Cons
A
- Pro ⇒ protection is immediate
- Cons
- Limited duration
- No memory
- Risk for subsequent infection w/ same pathogen
- Active immunization needed if available
- Potential for hypersentivitity rxn
6
Q
Passive Immunization
Examples
A
7
Q
Active Immunization
Overview
A
Prime the acquired immune response to viral antigens
- By natural infection or vaccination
-
Results in immunologic memory
- Prevent infection
- Reduce disease/pathology
- Limit transmission
- More effective secondary immune response on subsequent exposure
- Cheapest way to control infectious diseases
- Ex. Variola virus ⇒ Smallpox
- Toxoid vaccines protect against sx or pathology of disease
8
Q
Active Immunization
Requirements
A
Present protective Ag in appropriate context to promote immune recognition and response.
Expansion of protective, pathogen specific immune effector and memory lymphocytes.
9
Q
Vaccine Success
A
-
Efficacy
- Nature and complexity of protective immune response
- Ability to elicit appropriate responses by immunization
- Duration of immunity
- Safety
- Stability
- Cost
10
Q
Target Populations
A
11
Q
Vaccine Classes
A
- Live attenuated
- Whole virus
- Cross-reactive
- Whole killed
- Subunit (several types)
12
Q
Live Attenuated
Vaccines
A
Sufficient to induce a protective response but limited replication in vivo
-
Serial passage in cell culture
- Temperature-sensitive mutants
- Host-range mutants
- Ex. MMR
-
Targeted genetic modification
- Deletion of virulence factors
- Modify membrane proteins
- Creation of nutritional auxotrophs
- Ex. Salmonella typhi, Vibrio cholera
- Often results in a very robust response
13
Q
Antigenically Cross-reactive
Vaccines
A
Non-human pathogen that shares enough Ag to produce a cross-reactive, protective immune response
- Live pathogen given but cannot cause human disease
- Ex. Smallpox & Cowpox
- Ex. M. tuberculosis (TB) and M. bovis (BCG)
14
Q
Live Vaccine
Advantages
A
- Smaller doses required
- Stimulate immune response @ natural portal of entry
- Induces wide spectrum of responses
- More effectively mimic a natural immunity
- Longer long-lasting immunity
- Less frequent boosting
- Usu. cheaper
15
Q
Live Vaccines
Disadvantages
A
-
Safety issues
-
Reversion of virulence
- Oral polio vaccine combines w/ Sabin to regain virulence
-
Contamination
- Lubeck diaster ⇒ BCG vaccine contaminated w/ wild-type TB
- Yellow fever w/ HBV
-
Reversion of virulence
- Viral interference ⇒ competition from other viruses either natural or in vaccines
- Hard to store
- Side effects
- Vaccine related illnesses
16
Q
Live Vaccines
Contraindications
A
- Immunosuppressed individuals
- Pregnant women
17
Q
Whole Killed
Vaccines
A
-
Whole inactivated organisms
- Formalin, acetone, heat, irradiation
- Retained immunogenicity ⇒ induces a protective immune response
- Unable to replicate
- Lost ability to cause disease
- Ex. poliovirus, influenza virus, 1st gen Bordetella pertussis
18
Q
Subunit Vaccines
A
Specific component of organism containing necessary Ag determinants to elicit a protective immune response
Types:
- Toxoids
- Purified capsular polysaccharides
- Recombinant antigens
19
Q
Toxoid
Vaccines
A
- Inactivated toxins
- Induces neutralizing Ab to prevent toxin-mediated damage
- Does not prevent infection
- Ex. Diphtheria, tetanus, pertussis (acellular)
20
Q
Purified Capsular Polysaccharide
Vaccines
A
- Induce opsonizing Ab ⇒ promote phagocytosis and killing
- Infants do not respond well ⇒ T-cell independent
-
Capsular polysaccharide + protein carrier used for infants ⇒ hapten-carrier effect
- Elicits CD4+ T-cell help for Ab production
- Ex. Haemophilus influenzae (Hib), Strep. pneumoniae, Neisseria meningiditis
21
Q
Conjugate
Vaccines
A
Capsular polysaccharide + protein carrier
- Polysaccharide capsular Ag
- Target Ag for B-cell response
- Production of opsonizing Ab
- Protein Carrier
- Target Ag for T-cell response
- Elicits CD4+ T-cell help for Ab production
- Hapten-carrier effect
- Used for infants
22
Q
Recombinant Antigen
Vaccines
A
- Purified recombinant major surface protein
- Made using recombinant DNA in euk/prok systemis
- Induces neutralizing or opsonizing Ab
- Ex. Hep B surface Ag, Borrelia burgdorferi (Lyme’s)
23
Q
Inactivated and Subunit Vaccines
Advantages
A
- Safer ⇒ no reversion
- Increased stability during storage
- Little interference from other viruses
24
Q
Inactivated and Subunit Vaccines
Disadvantages
A
- Large amount of Ag required
- Requires adjuvants
-
Limited range of immune responses induced
- Do not necessarily mimic natural immunity
-
Low immunogenicity w/ shorter duration of protection
- Multiple booster shots usually needed
- Must have well-defined target Ag ⇒ limited complexity
- Subunit not always as effective as whole, killed vaccine
- Ex. influenza
25
Adjuvants
* **Components that non-specifically enhance immune responses**
* Purified PAMPs
* Monophosphoryl lipid A
* Muramyl dipeptide
* CpG DNA
* Cytokines
* Stimulates PRRs ⇒ TLR's
* **Stimulates APC's**
* Mφ and dendritic cells in draining LN
* ↑ cytokine production & costimulatory molecules
* **Modulate balance of Th1 vs Th2 type responses**
* **Antigen depot effect** ⇒ slow, sustained Ag release
* Aluminum salts
* Oil in water emulsions
* **Usually needed for subunit vaccines**
* **Tend to be responsible for minor, local side effects**
26
Live Attenuated & Recombinant Virus Vaccines
Immune Response
* **Endogenous** (MHC I) and **exogenous** (MHC II) Ag processing pathways potentially involved
* CD8+ T-cells, CD4+ T-cells, and B-cells activated
27
Whole Killed and Subunit Vaccines
Immune Response
* 1° involves **exogenous** Ag processing pathway
* CD4+ T-cells and B-cells activated
* Difficult to prime CD8+ T-cells
28
DNA Vaccines
* **Introduce plasmid DNA encoding pathogen Ag directly into host tissue**
* **Host cells take up the DNA, express, and present Ag**
* Endogenous Ag processing pathway
* Immunogenicity improved by:
* Adding DNA plasmids encoding cytokines or co-stimulatory molecules
* Novel delivery methods to enhance uptake ⇒ electroporation
* Currently experimental
29
Live Vectors
* **Introduce microbial genes into non-cytopathic virus or bacteria as vector**
* Organism replicates and produces protein ⇒ **self-replicating vaccine**
* Ex. Advenovirus, poxviruses, attenuated Samonella or Listeria
* Currently experimental
30
Heterologous Prime-Boost
Strategies
* Method:
* _Priming immunization_ w/ DNA based vaccine
* Second _booster immunization_ w/ live, viral vectored vaccine
* **↑ immunogenicity of subunit vaccines**
* Focuses immune response on vaccine Ag
31
Vaccine
Regulation
* **CDC and FDA**
* Maintain national surveillance system
* Monitor safety and side effects after licensure
* **Vaccine Adverse Event Reporting system (VAERS)**
* Online tool for providers and pts to report any problems or side effects
32
Public Health
Considerations
* Vaccine-preventable illness still prevalent
* Not all vaccines are 100% effective
* **Vaccine-preventable diseases occur in developed countries**
* Immunization programs neglected
* ↓ compliance w/ recommendations
* Concerns of real or perceived safety issues
* **Immunization programs in developing countries limited**
* Cost
* Limited resources
* Inadequate healthcare infrastructure
33
Hep B
Vaccine
Recombinant HbsAg
34
Haemophilus influenzae type B
Vaccine
Polysaccharide/protein conjugate
35
Polio
Vaccine
Whole killed virus
| (3 strains)
36
DTaP
Vaccine
Diphtheria & tetanus ⇒ toxids
Pertussis ⇒ acellular (toxoids + adhesins)
37
MMR
Vaccine
Measles, mumps, and rubella
## Footnote
**Live attenuated virus**
38
Varicella
Vaccine
Live attenuated virus
39
Neisseria meningitidis
Vaccine
Polysaccharide
40
Rotavirus
Vaccine
Live attenuated virus
41
Influenza
Vaccine
Trivalent inactivated (TIV)
or
Live attenuated (LAIV)
42
Recommended Childhood Vaccines
Summary
43
Strep. pneumoniae
Vaccine
Polysaccharide ⇒ over 60 y/o
Conjugate ⇒ infants
44
HPV
Vaccine
Subunit (virus-like particle) ⇒ adolescent children
45
Rabies
Vaccine
**Inactivated virus**
Given for recent bite, vets, animal caretakers.
46
Yellow Fever
Vaccine
**Live attenuated**
Given for travel to endemic areas.
47
Hep A
Vaccine
**Killed virus**
Given for travel to endemic areas.
48
Salmonella typhi
Vaccine
**Live attenuated or killed**
Given for travel to endemic areas.
