Vaccines (EXAM 3) Flashcards
Herd immunity
-most of the population is vaccinated to protect the few vulnerable
-reduces infection rate in the poulation
How do Vaccines impact Public health
-The number of incidences decreases
-Sanitation is a major factor in the decrease of water-borne diseases
How is active immunity obtained?
Natural: by infection
Artificial: by Vaccination
What are examples of diseases protected by active immunity?
-COVID, Measles, Mumps, Rubella (MMR), Polio, Hep A, Hep B
-safer alternative to natural infection
How is passive immunity obtained?
Natural: Maternal antibodies; IgA (breast milk), IgG (placenta)
Artificial: Monoclonal Ab -> Tetanus Antitoxin (TAT); Diphtheria antitoxin (DAT); Snake antivenins etc
-> Serum sickness can be caused by immune complexes due to passive immunization (mAb)
Difference between innate and adaptive immunity
Innate: immediate response, non-specific, no memory -> Macrophages, NK-cells, dendritic cells, Granulocytes
Adaptive: specific, take time build T-cells and Ab, strong immune memory
Difference in primary and secondary infection in an adaptive immune response
-Second exposure by the same pathogen leads to a strong and fast
immune response due to rapid clonal expansion of T and B cells
-Vaccination mimics the first infection
How do bodies recognize antigens?
TLRs recognize patterns on antigens (PAMPs) (like repeated patterns in aggregates of protein drugs)
-some TLRs are intercellular to bind endogenous antigens (viral) or broken particles of microbes
-C-type lectins recognize yeast-produced antigens
Process of Vaccine mediated active immunity
Antigen exposure -> APC take up and present antigen to CD4 Th cells -> CD4 TH cell secrete cytokines and activate CD8 T-cells and B -cells -> CD8 develop to CD8 cytotoxic Tcells and B-cells secrete Ab
-> formation of memory cells
Types of Vaccines
-Live, attenuated: most effective (polio-Sabin/BCG for TB)
-Dead or inactivated: (polio-Salk/choler vaccine)
-Sub-unit vaccine: hepatitis B, meningococcal, pneumococcal, Haemophilus influenza)
-Toxoids (diphtheria and tetanus)
What are ways to inactivate Bacteria or Viruses - Attenuation
-elimination of a pathogen’s virulence
-Serial passage in unnatural hosts (oral polio vaccine (Sabin),
MMR and BCG (bacterial)
-Mutagenic treatment (Nitrosoguanidine tx for Salmonella
typhii)
-Heat or chemical treatment (e.g. formaldehyde, phenol etc)
How does attenuation in an unnatural host work?
-Isolation from a patient -> grown in vitro in human cells
-infect monkey cells and passaged -> the virus mutates to survive and thereby loses its virulence
Advantages and Disadvantages of Live-attenuated
Advantages:
-produce more antigens -> strong cell and humoral (Ab) immune response
-fewer doses
Disadvantages:
-incorporation into host DNA, viral shedding, and contamination
-not suitable for immunosuppressed patients
-not for certain viruses (Hep, HIV, cancer-causing virus)
How can pathogens be inactivated for vaccines?
-Chemicals: formaldehyde, glutaraldehyde
-heat
-used in polio (Salk), typhoid, pertussis vaccines
Which vaccine has been attenuated genetically?
-Cholera vaccine (Vaxchora)
-through controlled deletions in the DNA
How are genetic-mediated attenuations different from Sabin-type attenuations?
Genetically attenuated vaccine cant get virulent again bc the gene causing the virulence is deleted
Inactivated Exotoxins
-Exotoxins of Cornybacterium depitheriae, Bordetella pertussis, Clostridium tetani
-Formaldehyde deactivates exotoxins through crosslinking (become toxoid)-> aggregation -> now susceptible to immune system - by adsorbing onto colloidal aluminum salts?
Subunit vaccines
What is the characteristics of Subunit vaccines?
Conbining parts of a pathogen that by themselves are not very virulent
-e.g. Vaccine against Anthrax -> B. anthracis + Virus antigen -> adsorbed onto an aluminium salt (adjuvant)
Polysaccharide Conjugate
Combining Bacterial cell wall polysaccharides (not enough antigenicity/PAMPs) with tetanus toxoid adjuvant
-e.g.: Haemophilus influenza type b (Hib)
Ingredients in Vaccines
Thimerosal - Preservative
Aluminum salts - Adjuvant
Sugar, gelatin - Stabilizer
Formaldehyde - inactivation agent
Neomycin - antibacterial
egg protein - cell culture material
Why do adjuvants cause a stronger immune response?
-increases the number of immune cells produced as a response (quantitative effect)
-Depot effect: adjuvanted antigens are exposed to the immune system for a longer time
-enhanced APC function bc of pattern recognition of TLR (aggregated)
-more cytokine release and better delivery into lymph nodes
Adjuvants used in Vaccines
-o/w emulsion with squalene
Moa SARS-Cov2 Vaccines
DNA Vaccines (AstraZeneca, JJ): non-replicating chimpanzee adenovirus to carry DNA coding for COVID spike protein -> gene to mRNA and mRNA to spike protein -> triggering an immune response
mRNA (Moderna/Pfizer): Lipid nanoparticle carries spike protein mRNA -> nanoparticle fuses with the cell membrane and releases the mRNA into cytosol -> translation into protein -> triggering immune response
What happens to the mRNA Vaccine once administered?
spike proteins ae build -> and picked up by APC and carried to adjacent lymph nodes
