9. Vaccines Flashcards
What is the story of vaccination discovery?
Modern day vaccination: Dr Eward Jenner (end of 18th century) - noticed that milkmaids didn’t catch smallpox as easily - inoculated a boy with cowpox - developed immunity against smallpox => full protection againts smallpox
When was smallpox officially eradicated?
1980
What are the earliest records of vaccination?
- 7th century - Indian Budhists drank snake venom
- 10th century variolation to prevent smallpox in China, India, Turkey
What is the chronological sequence of vaccine type development?
- Bacterial vaccines
- Viral vaccines
- Molecular vaccines
What is passive immunisation?
Passive immunisation - transfer of serum antibodies - passive because the organism didn’t produce Ab itself
Who first developed passive immunisation?
Emil von Behring - Nobel prize in 1901 - developed passive immunisation for diphteria:
immunized guinea pigs against diphtheria with heat-treated blood products from animals recovered - antibodies to the diphtheria toxin - protected guinea pigs later exposed to lethal doses - next showed they could cure diphtheria in an animal by injecting it with the blood products of an immunized animal - Ab transfer
What are the modes of antibody transfer from immune to non-immune organism?
Passive immunity - Ab transfer:
1) Natural: transfer of mother’s Ab via placenta / mother milk (colostrum)
2) Artificial: Ab derived from blood of immune people / non-human immune animals
What is anti-sera?
Anti-sera / antisera / Ab serum - blood serum with antibodies against specific antigens, injected to treat or protect against specific diseases
- typically produced in donor animal (horse / sheep): animal immunised with non-lethal dose of antigen (toxin / venom / pathogen derived antigen) - blood from animal collected - Ab purified
What are the current aplications of Ab transfers?
Current Ab transfer applications:
- Rapid treatment: during acute ilness don’t need to wait for imm syst to develop
- Prevention measure: after transplantation
What are the adv and disadv of Ab transfer?
Ab transfer:
Adv:
- rapid acting
- support deficient immune system (beneficial to high-risk individuals)
Disadv:
- protection fades
- intravenous injection (instead of intramuscular)
- serum sickness - first time Ab recognised as Ag - imm response
- expensive / complicated to manufacture
What are monoclonal antibodies?
Monoclonal antibodies - A type of protein that is made in the laboratory and can bind to certain targets in the body - onse specific Ab for one Ag produced
Nobel prize 1984 Cesar Milsten, Georges J.F. Kohler
What was the initail method for monoclonal antibody production?
What are the major adv of monoclonal antibodies?
Adv of monoclonal antibodies:
- Single specificity (monoclonal)
- Unlimited supply (hybridomas can divide continously + can be frozen)
- Rare specificity Ab can be isolated
- Ab can be engineered - new specificieties, efficiencies
- more safe, less toxic in canceer threatment than chemotherapy
How are animal antibodies humanised?
Mouse monoclonal Ab can be recognised as Ag - use human Ab + adapt epitopes for Ag - add complementarity determining region (CDR) produced by mouse cells for the specific Ag (won’t be recognised as Ag) - Ag bound by the engineered Ab but not recognised as foreign because human Ab core is used
What are the currently used methods for monoclonal antibody production?
What do therapeutic monoclonal antibodies target?
- Cytokines
- Growth factor receptors
- Check point inhibitors
What are the main principles in vaccination?
- Introduce imm syst to a pathogen in a controlled env
- Cause imm syst to remember pathogen and respond to it
- Enable imm syst to effectively clear the pathogen to prevent disease
What are the characteristics sought in vaccines?
- long lasting immunity
- safe
- stable
- easy to store and administer
- single dose
- affordable
- pathogen evolution-proof
What are the features of adaptive immune system?
What are the main immune system components used in vaccination?
- Ab / B cells
- CD4 T cells
- CD8 T cells
What are the developed vaccines for polio?
Different types of vaccined developed for polio:
- Inactivated (whole pathogen killed): inactivated by formalin Jonas Salk
- Live-attenuated (weakened pathogen form): Albert Sabin
How are chicken eggs used for vaccine production?
Chicken eggs - vertebrate hosts for viral replication - different viruses grow in different egg parts - difficult host because need skilled professional to precisely inject the virus into a specific part + conditions for storage
What are the limitations of traditional vaccine production methods?
What are sub-unit vaccines?
Not entire organism - use components - ex proteins
Adv: no extra pathogenic particles (ex DNA)
Disadv: proteins may differ when outside the organism; production expensive
What is a vector vaccine?
Vector vaccine - vaccine which uses a vector (ex virus) to deliver genetic material to be transcribed as mRNA in host cells to produce necessary molecules
What are the common examples of viral and bacterial vaccines?
Viral: influenza, polio, smallpox
Bacterial: meningitis, pneumonia, tuberculosis
What are VLPs?
Virus like particles (VLP) - mimic viruses but are not infectious - more safe to administer
- Non-enveloped VLPs - composed of 1+ viral structural proteins
- Enveloped VLPs consist of host cell membrane with viral proteins on outer surface
What are the types of vaccines types based on vector type?
What is the structure of outer membrane vesicle vaccine technology?
What is the structure of protein-polysaccharide conjugate vaccine technology?
What are the vaccine delivery routes?
Explain what is FluMist
What are vaccine adjuvants and why are they necessary?
Vaccine adjuvants - ingredient in vaccines - helps create a stronger immune response after the vaccine delivery
Essential for enhancing + directing adaptive imm response to vaccine Ag - response mediated by B and T cells
What are the main advantages of using an adjuvant?
Explain the sequence of events after immunisation with a vaccine containing AS01 chemical
AS01 - adjuvant
What is the role of DC in vaccination?
DCs interact with B and T cells to launch a specific, adaptive immune response to the pathogen
What are the specific roles of an adjuvant?
- extend presence of Ag
- locally activate macrophages and lymphocytes
- cupport local production of cytokines
- activate APCs, support migration and absorption, present Ag
What is the mechanism of action of an adjuvant?
Mimic microbe components which bind to PRRs on APCs
What are the benefits and risks of a vaccine adjuvant?
What are the disadvantages of live-attenuated vaccines compared to inactivated?
Live-attenuated can mutate - revertant mutants - don’t help to clear but spread the infection
How it is decided what type of polio vaccine to be approved in a country?
Depends on polop levels in the country - if eradicated or not
What are the advantages and risks of live-attenuated vaccines?
Define what is an antigenic drift?
Antigenic drift - viral genetic variation from mutation accumulation in the virus genes coding for virus-surface proteins that host antibodies recognize
What is the challenge of antigenic drift?
Antigenic drift -> person susceptible to same virus infection again - because antigenic drift has changed the virus’ antigenic properties enough that a person’s existing Ab won’t effectively recognize and neutralize the antigenically different flu viruses
What is the universal flu vaccine?
Universal flu vaccine - flu vaccine effective against all influenza strains regardless of the virus sub type, antigenic drift or antigenic shift.
How is the univeral flu vaccine created?
Vaccine includes mRNAs for a key virus protein called hemagglutinin (HA) from all 20 influenza types
What are the steps in vaccine development?
What are the steps in vaccine development?
What are the coronaviruses that have emerged?
- SARS-CoV (Nov 2002) - didn’t spread into a global problem
- MERS-CoV (Jan 2012) - didn’t spread much beyond the middle east
- SARS-CoV2 (2019) - global pandemic
Why was SARS-CoV2 good at spreading?
- respiratory virus but can infect many tissues
- trnasmitted before symptoms appear
What is the infection mechanism of SARS-CoV2?
Surface spike glycoprotein - binds to angiotensin - converts enzyme 2 receptor (on many mammalian cells)
Spike protein - Ag of interest in vaccine
What are the tools used to battle COVID-19?
- Anti-virals
- Monoclonal antibodies (against spiek proteins)
- Corticosteroids (supress hyperimmune response)
- Vaccines (preventative)
Why was COVID19 vaccines developed so quickly?
- more efficient technology/methods
- years of advanced research
- Phase II and III trials performed simultaneously
- a few steps skipped
- supercharged funding
What are the existing vaccine strategies? What are the specific COVID-19 vaccines using those strategies?
Explain Sinopharm vaccine
Sinopharm:
- inactivated SARS-CoV2
Explain Oxford-AstraZeneca vaccine
Oxford-AstraZeneca:
- virus vectored - ChAdOx1 - chimpanzee adenovirus
Explain Gamaleya (Sputnik V) vaccine
Gamaleya (Sputnik V) - virus vectored - identical strategy to Oxford-AstraZeneca - only a combination of 2 adenoviruses used
Explain Pfizer-BioNTech vaccine
Pfizer-BioNTech: mRNA (no additional adjuvant - nanoparticle surface acts as an adjuvant) - mRNA codes for a modified S protein - 2 am a substitutions compared to WT
Explain Moderna vaccine
Moderna: mRNA (same as Pfizer-BioNTech just the nanoparticle a bit different + higher Ag dose)
Explain EpiVacCorona and Novavax vaccines
EpiVacCorona (Russian - little info) / Novavax: protein subunit
What are the challenges related to effective vaccine administration across the world?
