Lecture 1: Vaccines Flashcards
Name 2 general pathogen control strategies and their properties (3P each)
Vaccination
→ prior to clinical manifestation
→ requires an intact immune system
→ induces more or less stable immune response
Therapy
→ Intervention after occurrence of clinical disease
→does not require immune system
→ patients can be reinfected
Name diseases where vaccination was a great success
Diptheria
Measles
→ SSPE disease
Mumps
Pertussis
Polio
→ paralysis
→ attenuated live vaccine
Rubella
Tetanus
Haemophilus influenzae type b
→ invasie Hib disease
→ conjugated vaccine
Hepatitis B
Which research topics to study vaccine ?
→ basic research for vaccine developement
→ implementation research to implement social, cultural, geographic, economic factors
Why need for development of antivirals ?
Examples of viruses
→ Development difficult
→ Conserved target/existing antivirals
→ Development of antivirals is faster/easier
→ Hepatitis
→ Ebolavirus
→ Emerging viruses like Chikungunya, Dengue, Coronavirus
→ HIV
→ Influenza
→ Herpesvirus
Whats passive immunization ?
examples
Transfer of immune system compounds like T cells or antibodies
examples
→ Synagis to prevent RSV via humanized monoclonal antibody targeting RSV F
→ Antibody cocktail for Ebola
→ maternal transfer of antibodies to fetus
Adaptive immune response overview
Humoral
→ extracellular microbes that can be recognized via B lymphocytes to secrete antibodies in serum
→ blocking of infection and eliminate extracellular microbes
Cell mediated
1→ Phagocytosed microbes in macrophages
→ T Helper lymphocytes that activate macrophages to kill phagocytosed microbes, inflammation and activation of B and T cells
2→ Intracellular microbes
→ cytotoxic T lymphocytes kill infected cells and eliminate reservoir of infection
What are the 2 major vaccine-induced effector functions in virus infection ?
→ neutralizing antibodies via B cells (successfull vaccines
→ cell mediated cytotoxicity via CD8+ T cells
Lymphocyte receptors
How is diversity generated ?
3 complemetarity determing region that bind antigen
→ different ligands for B and T cell receptors
B cell = soluble antigen or extracell. pathogen
T cell = epitope/peptide of APCs (MHC)
Diversity
→ shaping of lymphocyte receptor repertoir during lymphocyte development
→ V-D-J joining, addition of N/P nucleotides, transcription and RNA processing
→ 10^11 to 10^18 different options
→ clonal selection with somatic hypermutation
8 general vaccination strategies
attenuation
→ replication competent natural virus vaccine
inactivation
→ inactivated virus vaccine
Fractionation
→ non recombinant, purified subunit vaccine
cloning in bacteria cell (Recombinant vaccine)
Cloning
→ replication competent virus vector vaccine
→ DNA vaccine
Expression
→ Protein
→ Subunit vacine
→ Virus like particle vaccine
Replication competent vaccines vs inactivated vaccines
→ mode
→ example virus
→ 2 example vaccines
→ + / -
attenuation
→ reduction of virulence
Example
→ Polio virus
2 vaccines
→ oral attenuated replication competent vaccine (OPV) thats a mixture of 3 major strains which has been passaged in primate cells to decrease virulence
→ risk of reversion and disease but immune response potent
→ empirically, tough to develop
→ inactivated injectable vaccine (IPV) that contains a mixture of WT poliovirus strains of each serotype that have been killed with formaldehyd
→ no risk of reversion but less potent immmune reaction, multi
Special about Influenza virus vaccine
inactivated vaccine
segments, antigenic shift can induce new strains
→ Vaccine efficacy varies accross years
Why would anyone use viral vectors for vaccination ?
Example
Different examples of virus vectors
→ highly specific gene delivery to target cells
→ induction of roboust adaptive immune response
→ activation of strong innate immune response (TLR based)
→ combining advantages of both replication competent and inactivated vaccines
e.g. Ebola virus vaccine - VSV vector
Virus vectors
→ Retro-, Lentivirus
→ Vaccinia-, Adenovirus
→ AstraZeneka, J&J
→ Adeno associated virus
→ Cytomegalovirus
→ Sendai virus
DNA vaccines
→ mechanism
→ limitations
DNA
inject into muscle, uptaken by DCs
→ transfection
→ expression of antigen to activate antigen presentation mechanism
limitations
→ limited antigenicity, mostly T cell response, (incorporation of DNA, induction of anti DNA antibodies)
RNA
→ mechanism
Liponanoparticle incorporating mRNA
→ uptake by immune cells
→ expression of antigens to activate immune system
Advantages
→ faster approval
→ T/B cell response
→ no genomic incorporation
Protein vaccines
→ mechanism
→ Example
→ limitations
Immunization with a protein antigen
→ recombinant proteins
Limitations
→ often not sufficiently immunogenic
Example
→ Shingrix, recombinant Varicella Zoster virus glycoprotein E
→ subunit vaccine Novavax
How to stimulate immunogenicity in protein vaccines ?
Example vaccine
Mechanims
Multimerization
→ for example VLP´s or nanoparticles
Examples
→ Hepatitis B
→ virus surface antigen (HBs) particles produced in yeast, elicts roboust Ab levels
Mechanism
→ exposes antigen on surface
→ antigen presentation B cell receptor clustering, T cell engangement, long term immunity enhanced
also works while transplanting proteins to nanoparticles that enhances binding antibodies and neutralizing antibodies, just need to know which epitope is essential and then you can transplant this epitope (computer)
