Lecture 1: Vaccines

Question 1

Name 2 general pathogen control strategies and their properties (3P each)

Answer 1

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

Question 2

Name diseases where vaccination was a great success

Answer 2

Diptheria

Measles
→ SSPE disease

Mumps

Pertussis

Polio
→ paralysis
→ attenuated live vaccine

Rubella

Tetanus

Haemophilus influenzae type b
→ invasie Hib disease
→ conjugated vaccine

Hepatitis B

Question 3

Which research topics to study vaccine ?

Answer 3

→ basic research for vaccine developement

→ implementation research to implement social, cultural, geographic, economic factors

Question 4

Why need for development of antivirals ?

Examples of viruses

Answer 4

→ Development difficult
→ Conserved target/existing antivirals
→ Development of antivirals is faster/easier

→ Hepatitis
→ Ebolavirus
→ Emerging viruses like Chikungunya, Dengue, Coronavirus
→ HIV
→ Influenza
→ Herpesvirus

Question 5

Whats passive immunization ?

examples

Answer 5

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

Question 6

Adaptive immune response overview

Answer 6

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

Question 7

What are the 2 major vaccine-induced effector functions in virus infection ?

Answer 7

→ neutralizing antibodies via B cells (successfull vaccines
→ cell mediated cytotoxicity via CD8+ T cells

Question 8

Lymphocyte receptors

How is diversity generated ?

Answer 8

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

Question 9

8 general vaccination strategies

Answer 9

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

Question 10

Replication competent vaccines vs inactivated vaccines

→ mode
→ example virus
→ 2 example vaccines
→ + / -

Answer 10

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

Question 11

Special about Influenza virus vaccine

Answer 11

inactivated vaccine

segments, antigenic shift can induce new strains
→ Vaccine efficacy varies accross years

Question 12

Why would anyone use viral vectors for vaccination ?

Example

Different examples of virus vectors

Answer 12

→ 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

Question 13

DNA vaccines
→ mechanism
→ limitations

Answer 13

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)

Question 14

RNA
→ mechanism

Answer 14

Liponanoparticle incorporating mRNA
→ uptake by immune cells
→ expression of antigens to activate immune system

Advantages
→ faster approval
→ T/B cell response
→ no genomic incorporation

Question 15

Protein vaccines
→ mechanism
→ Example
→ limitations

Answer 15

Immunization with a protein antigen
→ recombinant proteins

Limitations
→ often not sufficiently immunogenic

Example
→ Shingrix, recombinant Varicella Zoster virus glycoprotein E
→ subunit vaccine Novavax

Question 16

How to stimulate immunogenicity in protein vaccines ?

Example vaccine

Mechanims

Answer 16

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)