Vaccination and Immunization

• Briefly describe passive immunization
  • Passive immunization occurs with the transfer of preformed antibodies to an unimmunized individual, causing short-term immunity.
  • Sources
    • Natural sources: maternal antibodies via placenta and breast milk
    • Artificial sources: human immune gamma globulin, anti-venom, anti-toxins
• Briefly describe active immunization
  • Active immunization occurs with exposure of an unimmunized individual to a pathogenic agent, casing long-term immunity.
  • Types
    • Natural active immunization: Exposure to antigen i.e. VZV
    • Artificial active immunization: vaccines i.e. PCV

Distinguish between passive and active immunity

• Briefly describe vaccination
  • Vaccination is the process of stimulating protective and adaptive immune responses against microbes by exposure to non-pathogenic forms or components of the microbes.
  • Small pox is the only disease to be intentionally eradicated from the earth.
  • Polio has been eliminated and is on its way to eradication (foci still exists e.g. in refugee camps)
  • The aim of vaccination is to induce a protective immune reaction without much of the necessary adverse effects.
  • After elimination of the antigens (Cell-mediated and humoral response) and immunological memory is formed (persistence of antibodies and generation of memory cells that can rapidly reactivate upon subsequent exposure to the same pathogen)

Distinguish between vaccination and immunization

• What is the clinical utility of vaccines
  • Individual protection
  • Protection of unvaccinated population: by reducing person-person transmission and limiting the risk for individuals to be exposed
  • Herd or community protection: (requires large proportion, 75-95%, immunity in a special group that plays a key role in transmission of the disease, is often essential for the success of vaccination programs, such as measles)
  • Indirect protection of infants in their first months of life: via vaccination of pregnant women and passive immunity through the placenta, concept has been successfully established for tetanus, influenza and pertussis)
• Briefly describe Live-attenuated vaccines
  • Live attenuated vaccines contain pathogens that have been weakened, altered or selected to be less virulent than their wild-types.
  • Techniques include:
    • passing the virus through a series of in-vitro cell cultures (chick embryo cells),
    • low-temperature passages (25*C),
  • These viruses present the same antigens as the wild-type virus. They induce robust cell-mediated and antibody responses that confer long-term immunity.
  • They also induce herd immunity via excretion of viral particles (viral shedding) which may indirectly “vaccinate” individuals living in the environment of the vaccine.
• Give examples of Live-attenuated Vaccines
  • MMR
  • Yellow Fever
  • OPV
  • Chicken pox (varicella)
  • **BCG (**Only bacterial live attenuated vaccine – Mycobacterium bovis has been attenuated through cultures over the years)
• What are the limitations of Live-attenuated Vaccines
  • Clinical disease can occur after vaccination (vaccine-induced symptoms are milder though)
  • Immunocompromised individuals are at risk of unregulated pathogen replication (leads to severe infection or death)
  • Potential to revert back to a form able to cause disease (very rare e.g. OPV)
  • Contraindicated in immunosuppressed and pregnancy
• Briefly describe Inactivated whole pathogen vaccines
  • Inactivated vaccines are produced by inactivating preparations of whole pathogens (heat, radiation, chemicals such as formalin or formaldehyde)
  • Inactivation make the microorganisms stable
  • These vaccines do not require refrigeration but can be freeze dried.
• Give examples of Inactivated whole pathogen vaccines
  • Inactivated PV (Salk-IPV)
  • whole-cell pertussis (wP)
  • Rabies Vaccine
  • Hepatitis A Vaccine
• Describe the various Sub-unit vaccines giving examples under each
  • Protein based sub-unit vaccines
    • Recombinant Hepatitis B vaccine – produced via recombinant genetic engineering – gene for HBsAg is inserted into appropriate vectors for production in yeast (Engerix-B, GSK, Recombivax-HB, MSD) or mammalian cells (GenHevac-B, Sanofi Pasteur)
    • Recombinant malaria vaccine (RTS, S/ASO1, Mosquirix)
    • Acellular pertussis vaccine
  • Polysaccharide vaccine
    • Largely ineffective in children <2y of age as immune system is not mature enough to mount a response
  • Polysaccharide conjugate vaccine (second gen
    • Polysaccharides coupled to protein to improve its immunogenicity.
    • Examples:
      • Pneumoccoccal Conjugate Vaccine,
      • Haemophilus influenza Type B Vaccine
      • Meningococcal Vacine
  • Virus-Like Protein based vaccine
    • Viral particle that lacks the viralgenome
    • Examples:
      • HPV vaccines (Cervarix, GSK; Gardasil 9. MSD)
• Briefly describe Toxoid vaccines
  • Vaccines against Clostridium tetani, Clostridium difficile or Corynebacterium diptheria are produced by detoxifying the toxin using heat, chemicals (formaldehyde) or both.
  • Toxoids are no longer pathogenic but retain their ability to induce neutralizing antibodies.
• Briefly describe DNA vaccines
  • Naked plasmid DNA (not attached to vectors), still in the experimental stage of development.
  • Injected IM
    • Skeletal muscles and APCs synthesize antigens which stimulate immune system.
  • Delivery systems (gene guns) deliver DNA coated with gold micro projectiles intradermally (skin has better immune surveillance with APCs and innate cells)
• Give trial examples of DNA vaccines
  • Rabies vaccine
  • Malaria vaccine
• Give FDA approved examples of DNA vaccines
  • Veterinary West Nile Vaccine for Horses
  • Apex IHN for Salmon Fish
• What are the advantages of DNA vaccines
  • Versatile (both cellular and humoral immunity)
  • Flexibility (can be fused with multiple epitopes)
  • No risk of infectivity
  • Stability (does not require cold chain storage and transportation)
  • Cheaper and simpler production
• What is the disadvantage of DNA vaccines
  • Genomic integration is possibly linked with disease causation????
  ***I haven’t done my research on this. Take it with a grain of salt.
• Briefly describe mRNA vaccines
  • mRNA is translated into antigens in muscle cells and APCs.
  • Naked mRNA is quickly degraded by extracellular RNAses and is not internalized efficiently (reduces the risk for metabolic toxicity and genomic integration)
• Briefly describe Recombinant vector vaccines
  • Uses either attenuated virus or microbe to introduce microbial DNA into body cells, antigen against which immunity is sough comes from a foreign transgene inserted into the vector.
  • Vectors include adenoviruses and CMV
• List the routes of administration of vaccines
  • Conventional needle injections
    • Intramuscular (DTwP, DTaaP, DT, Td, TT, HepB, IPV, HiB, PCV-7)
    • Subcutaneous (Measles, Yellow Fever)
    • Intradermal (BCG)
  • Alternative routes
    • Intranasal (Live attenuated influenza vaccine)
    • Oral (OPV, Cholera vaccine, Rotavirus)
    • Sublingual
    • Through the skin using microneedle or needle-free devices
• What are some adverse effects of vaccines
  • Intussusception with the first rotavirus vaccine
  • Narcolepsy with the adjuvanted H1N1 influenza vaccine
• Summarize the different types of vaccines giving examples under each
  1. Live-attenuated vaccines
     • Contains pathogens that have been weekened, altered or selected to be less virulent than their wild-types.
     • Examples: MMR, Yellow Fever, Sabin OPV, Varicella, BCG (Only bacterial Live-attenuated vaccine, M-bovis)
  2. Inactivated (Killed) vaccine
     • Inactivated vaccines produced by inactivating preparations of whole pathogens using heat, chemicals, and radiation.
     • Examples: Salk IPV, whole-cell pertussis wP, rabies, Hepatitis A Vaccine
  3. Sub-unit vaccines
     • Protein sub-unit vaccine
       • Produced via recombinant genetic engineering
       • Examples: Recombinant Hepatitis B vaccine (Engerix-B, GSK; Recombivax-HB, MSD), Recombinant malaria vaccine (RTS, S/AS01, Mosquirix), Acellular Pertussis vaccine aP, Novavax Covid-19
     • Polysaccharide conjugate vaccine
       • Polysaccharide coupled to proteins to improve immunogenicity
       • Example: Pneumococcal conjugate vaccine, Hemophilus Influenza Type B, Neisseria Meningitidis
     • Viral-like protein based vaccine
       • Viral particles that lack the viral genome
       • Examples: HPV vaccine (Cervarix [bivalent – 16 & 18], GSK; Gardasil 9vHPV, MSD)
  4. Toxoid vaccines
     • Produced by detoxifying toxins using heat, chemicals, or both
     • Examples; Tetanus toxoid, Clostridium difficile, Corynebacterium diphtheria
  5. DNA vaccine
     • Naked plasmid DNA injected IM to stimulate muscle and APC synthesis of antigens
     • Trial examples: Rabies vaccine, Malaria vaccine
     • FDA approved examples: Veterinary West Nile Vacine for Horses, Apex INH for Salmon Fish
  6. mRNA vaccines
     • mRNA Injected IM to stimulate antigen production by muscles and APCs
     • Examples: Pfizer-Biontech, Moderna
  7. Recombinant vector vaccines
     • Uses either attenuated virus (adenovirus, CMV) or microbes with a foreign inserted transgene to introduce microbial DNA into body cells
     • Examples: Astrazeneca-Oxford vaccine, Johnson & Johnson

Distinguish between the Salk-IPV and Sabin-OPV

• Outline the vaccines given under the Kenya Expanded Programme on Immunization
  • Primary infant and adolescent Vaccination Schedule
    • BCG: Birth
    • OPV: Birth, 6, 10, 14 weeks
    • Rotavirus: 6, 10 weeks
    • DTwPHiBHeP: 6, 10, 14 weeks
    • Pneumococcal conjugate vaccine: 6, 10, 14, weeks
    • IPV: 14 weeks
    • Yellow fever vaccine: 9 months
    • Measles: 9, 18 months (not available in all parts of the country)
    • HPV: 10 years; + 6 months (from January 2018)
  • Adult Vaccination schedule
    • High-risk groups (Health workers)
      • Hepatitis B adult dose vaccine: 1st contact; +1, +1months
    • Gestation
      • TT: 1st contact pregnancy; +1, +6 months; +1, +1 year
    • Travellers
      • Typhoid fever vaccine: 1st contact traveller
• What are Vaccine adjuvants
  • Vaccine adjuvants are substances that enhance and modulate the immunogenicity of the antigen
• Give examples of vaccine adjuvants
  • Alum: Aluminium salts, activates innate immune cells
  • Virosomes: spherical lipid layers, assemble in vitro with viral proteins to resemble viral membranes
• What is the utility of vaccine adjuvants
  • Adjuvants are used for subunit vaccines because they contain fewer antigens and lack intrinsic components present in whole pathogens
  • Virosomes are used with Influenza and Hepatitis A vaccine
  • Adjuvants reduce the number of doses needed