Vaccines (part A and part B) Flashcards
What are the principles and aims for vaccines?
Principles: Prime the adaptive immune system to the antigen of a particular microbe –> on first contact with the live organism = rapid and effective secondary immune response will be induced by memory T and B cells
Aims
- Public health: Eradication of the dsease (e.g. smallpox, eradication of polio is being attempted)
- Individual level: protect the individual against symptoms or pathology from infectious disease (diphtheria and tetanus vaacines)
What roles did Edward Jenner and Louis Pasteur play in development and understanding of modern vaccination
Edward Jenner
- First to publish scientific results
- Observed that milk maids with cowpox (mild disease) were resistant to smallpox
- Smallpox eradication in 1977
- Cowpox and smallpox viruses share some surface antigens, immunization with cowpox induces antibodies against cowpox surface antigens , cowpox antibodies to and neutralize the smallpox virus
Louis Pasteur (daddy of microbiology) –> 1822-1985
- Developed process of sterilisation (pasteruisation)
- Developed idea of attenuated microbes (weakened organisms)
- Pasteur developed vaccines for chickenpox, cholera, rabies and anthrax by using attenuated pathogens
Why are vaccines so effective?
- Most effective public health tool –> cost effective
- save many lives (2.5 millions each year from diptheria, tetanus, pertussis and measles)
- estimated 1.5 million people still died from a vaccine-preventable disease (result of poor vaccine uptake and sypply to remote and war-torn areas)
How do vaccines work to prepare the immune system?
Clue: 3 steps
- Expose a patient to an antigen from a pathogen
- Can be whole organism: live (attenuated), inactivated (killed) or components (e.g. protein, polysaccharide)
- must be a capable of producing a specific immune response
- Patients immune system reponds:
- mounts limitied response = primary immune reponse
- followed by memory cells (years to life time immunity)
- Subsequent exposure to the wild-type pathogen/antigen:
- Immune system will be challenged
- Memory cells and long-lived plasma cells producing antibodies
- Will respond quickly to kill/neutralize pathogen and avoid illness = secondary immune response
What are the different types of vaccines?
- Live attenuated (viral, bacterial)
- Inactivated (whole virus, whole bacteria)
- Fractions (toxoids, protein subunits, polysaccharides, conjugates)
- What are live attenuated vaccines?
- Provide example and discuss how long vaccines work
- Discuss advantages and disadvantages
- Usually created from naturally occuring pathogen
- Can still infect people but very rarely cause serious disease
- Viruses are weakened/attenuated by growing them repeatedly in lab under nourishing conditions –> virluence factors are lost
- Mostly possible with viruses due to relatively simple genome (measles, mumps, rubella, oral polio)
* Also possible for bacterial (BCG, oral typhoid)
3.
- Advantages: Replicated immune response is closer to the natural infection, usually effective with one dose
- Disadvantages: Generally not suitable for immunocompromised or during pregnancy, concern about recreating a wild-type pathogen that can cause disease, fragile –> must be stored carefully and diffcult to get to remote places
- Oral polio vaccine (OPV, sabin) –> some of the 1st doses of vaccine can cause paralysis
What is the MMR vaccine and desribe how the doses are given
MMR = measles, mumps, rubella
- Contain live attenuated viruses: measles, mumps, rubella and varicella (for priorix-tetra)
- Requires 2 doeses: 1 and 4 years (1st dose gives 95% immunity while 2nd dose gives 99-100 %)
Contraindication
- Immunosuppressed, pregnancy (need to wait 28 days after vaccine)
What are inactivated (killed) vaccines, also discuss their advantages and disadvantages
- Inactivated vaccines contained killed, whole microorganisms
- Cannot replicate and cause an infection
- Stimulate a protective immune response
- Viruses are inactivated with chemicals such as formaldehyde and glutaraldehyde; antigens still present
Examples: polio, influenza, hep A, pertussis, cholera, typhoid
Advantages
- No chance of creating live pathogen (no reversion to virlulent form)
- Safe to use in immunocompromised individuals
Disadvantages
- cannot replicate and thus generally not as effective
- limited immune response –> usually antibody only
- usually required 3-5 doses for signficant immunological memory
What are the differences between the attenuated and inactivated(killed) versions of the Polio vaccine
Inactivated polio vaccine (IPV): SALK 1954
- Injection plus alum (adjuvant)
- Can be given with other childhood vaccines
- Risk if inadequately killed
- Developed countries are using this as there is limited possibility of spread
- three types of inactivated polio viruses –> type 1: mahoney strain, type 2: MEF-1, type 3: Saukett strain
Attenuated oral polio vaccine (OPV), Sabin vaccine: 1960
- Oral route
- Boosts IgA immunity, Herd immunity
- Reversion to virulence
- Reproduces natural infection –>produces mucuous membrane immune mecahnism which stops transmission
What are toxoid and subunit vaccines and what is the difference between them?
Toxoid Vaccine
- Modified bacterial entotoxins
- Toxins are treated with iodine, pepsin, ascorbic acid or formalin to reduce toxicity while retaining ability to stimulate immune response
- Antibodies directed at the toxoid neutralize exotoxins before they reach the target cell
- Examples: diphtheria and tetanus vaccines contain toxoids which stimulate an immune response
- Vaccine = infanrix hexa
Protein Subunit Vaccines
Only the immunogenic determinant or antigenic molecules critical for protection against pathogen
- Originally purified proteins from infected patients but now use recombinant DNA techonology to produce specific proteins in yeast
- Examples: Hepatitis B virus vaccine –> composed of only the surface proteins; HBsAg
- HPV vaccine- composed of the viral major capsid protein
- Influenza virus vaccine- composed of the hemmagglutinin and neuraminidase subunits
How are polysaccharide vaccines more effective against encapsulated bacterial pathogens?
- Revolutionised vaccine approach against encapsulated bacterial pathogens
- Hummoral immunity (antibodies) is critical for protection against encapsulated bacteria but:
>Most polysaccharides are T-independent antigens and are usually poor immunogens –> no immunological memory
>Children upto the age of 2 respond poorly to these antigens, particularly type 2 T-independent antigens –> at high risk e.g. S.pneuomoniae and H. influenzae
- By linking these outer coat polysaccharides to other immunogenic proteins (e.g. toxins), immune system can be led to recognize the polysaccharide as if it were a protein antigen –> T cell dependent mechanism –> strong + memory
Describe the H.influenzae type b conjugate vaccine
- Out of the 6 bacterial capsule sub types, type B causes 95% infections
- Conjugated the polysaccharide to T-dependent antigen (tetanus toxoid)
- Need 3-4 doses to induce good immunity
What are adjuvants and how do they promote the immune reaction?
Adjuvant is a substance added to vaccine to increase the body’s immune response to the vaccine
- Inducing activation of Toll-like receptors (TLR) on dendritic cells to improve antigen presentation
- Forming an antigen depot which allows antigen to persist and leak out slowly over time
- Freund’s complete ajduvant (water-in-oil emulsion and dead mycobacteria –> effective but suitable for animals only
- Aluminium salts are now most commonly used and are powerful adjuvants
What is Herd immunity?
Herd Immunity = if enough individuals in a population are immunized, this will reduce or stop transmission of the infection
- When too many parents decide that their child will not be immunized, because they think the risk to child is low
- This may contribute to the disease becoming more common
- Herd immunity also protects those that cannot be immunized due to weak immune system (newborne, pregnancy, illness, old)
What are some of the adverse reactions of vaccination?
Local
- Pain, swelling, redness at site of injection
- Common with inactivated(killed) vaccines
- Usually mild and self-limited
Systemic
- fever, malaise, headache
- Faint
- Non-specific
- May be unrelated to vaccine
- Anaphylaxis
Anaphylaxis –> most severe adverse effect
>happens within 15 minutes
>rare but can be life threatening
>Adminster epinephrine and antihistamines
What are some of the symptoms of anaphylaxis?
What are some of the differences between chemotherapy and vaccination
Chemotherapy: Given after exposure to infection (offers short-term that wanes once drugs is no longer given)
Vaccination: Given before exposure (can give protection for years to life-time without repeated treatment)
