Viral vaccines Flashcards
What is passive imminuty?
The administration of antibodies to an unimmunized person from an immune subject to provide temporary protection against a microbial agent or toxin
What are the functions of B cells? (3)
Immunoglobulin production
Antigen presentation
T cell activation/regulation
What are the functions of antibodies? (3)
Neutralisation
Fc-receptor interactions (leading to ADCP and ADCC)
Complement activation
How does neutralisation work?
Antibodies bind to pathogens, forming an immune complex, which can then be taken up by macrophages and neutralised
What are the two main mechanisms that happen as a result of Fc-receptor interactions?
Antibody-dependent cellular phagocytosis (ADCP)
Antibody-dependent cytotoxicity (ADCC)
How does antibody-dependent phagocytosis work?
Similar to neutralisation. Antibodies bind and coat (much like opsonization), then Fc receptor binds to macrophage surface, leading to endocytosis (becomes a phagosome) in which lysosomes break down the complex
How does antibody-dependent cytotoxicity work?
Antibodies bind, Fc receptors on NK cells recognize Fc. Crosslinking leads to the NK cell degranulating and killing the cell through apoptosis.
What is natural passive immunization?
Mother to child
How is maternal IgG transported to the fetus?
Across the placenta via the neonatal Fc receptor (FcRn)
How can we improve newborn immunity? (2)
Vaccinate the mother (active immunization)
Breastfeed
What is the best timing to vaccinate future mothers? What to consider?
It depends. Live vaccines such as MMR (measles, mumps, rubella) can cause adverse pregnancy outcomes, so this is best done before conception. Pertussis and RSV vaccines can be given during pregnancy.
What are indications for (artificial) passive immunisation?
- When people cannot synthesize sufficient antibodies:
- primary antibody deficiencies (like XLA),
- acquired antibody deficiencies (chemo, immunosuppressive medication)
- newborns, especially those at risk - When exposure to a disease is likely to cause complications, such as in rabies
What is immunoglobulin replacement therapy and when is it used?
It is a maintenance infusion from serum of 1000-15000 donors for people with primary antibody deficiencies (such as XLA)
When are anti-rabies immunoglobulins given?
If a patient has not been previously vaccinated for rabies. It is given in combination with 4 vaccinations. If the patient has been vaccinated, 2 vaccinations are given and no IGs
What is often given instead of human anti-rabies IGs and why?
horse anti-rabies IG, since it is very expensive and is not available in many low income coutnries
What are side effects of passive immunization?
Allergic response (especially when produced in animals)
Serum sickness to non-human proteins
Local response (irritation)
What are the benefits of live-attenuated vaccines?
Immune responses most closely resemble natural immunity, including CD4, CD8 and B cells, and protection is often long-lasting.
What are the benefits of inactivated vaccines?
They are safe and more like the real thing.
What type of immune response is lacking after vaccination with inactivated vaccines?
CD8 T cell responses, since no viral proteins are being produced endogenously. Adjuvants and multiple doses are often required and immunity is short-lasting.
How are inactivated vaccines inactivated?
Heat, chemical (formalin) or irradiation
What is the issue with paramyxovirus and feline coronavirus inactivated vaccines?
There is a risk for priming for enhanced disease
How are subunit vaccines produced these days?
The gene of interest is expressed in bacteria, yeast or cells, and the proteins made are purified. Usually these are capsid or membrane proteins
What are the pros of using subunit vaccines?
Selection of the subunit facilitates a targeted immune response, and this method allows for the differentiation of vaccinated animals from infected animals
What is DIVA and when can it be used?
Differentiating Infected from Vaccinated Animals. It is possible with subunit vaccines, VLP vaccines and vector-based vaccines
What is the problem with subunit vaccines?
They are poorly immunogenic, often requiring multiple doses and short-lasting immunity. They lead to poor induction of CD8 T cell responses since no proteins are endogenously being produced.
What are different mechanisms adjuvants can use? (4)
(1) stabilize antigen or delay release
(2) Enhance uptake by macrophages
(3) Activate co-stimulatory molecules (innate or Th2 skewing for antibody production)
(4) Improve delivery to the cytosol (for CTL responses)
Why is DNA vaccine administration a challenge? How do they try to administer?
Getting DNA into host cells is difficult. Now they use Microneedles or CO2 gas injectors to get enough DNA into the skin to enhance uptake.
What are the disadvantages of DNA vaccines?
Administration is difficult and the percieved risk of genome integration by the public is an issue
What are the downsides of mRNA vaccines?
Stability, there are size contraints (it has to fit in the alphavirus or lipid nanoparticle) and it forms dsRNA, which is a potent trigger of the innate immune response (though this can also be a benefit)
What are pros of DC vaccines?
They indice cellular immune responses well, including CTLs. They are also tailor-made (though this is also a downside)
WHat are cons of DC vaccines?
They are labor-intensive and expensive because they are tailor-made
What are things you need to think abour when designing a vector-based vaccine? (4)
Which vector?
Which antigen and what type?
Dose (incuding how many)?
Route of administration?
What do you need to think about when choosing a vector?
Whether it’s replication competent of deficient
Pre-existing immunity
Types of immunity induced (depends on what is needed to protect against a pathogen)
What is the issue with adenoviruses and how can we go around that? (2)
Pre-existing immunity against adenoviruses. We can go around that by choosing adenoviruses that are not very prevalent or choosing non-human adenoviruses.
What are fve key reasons bacterial vaccines are important?
Disease prevention
Eradication and control
Protection of vulnerable populations
Global health equity
Prevention of antimicrobial resistance
What are four types of bacterial vaccines an example of each?
Toxoid vaccine: Tetanus
Inactivated: Bordetella pertussis
Subunit: Pertussis
Conjugate: Haemophilus influenzae type b
Why are conjugate vaccines needed instead of polysaccharide vaccines alone?
Polysaccharides do not induce a strong T cell response (since DCs can’t present them), which is weak in youg children. Conjugate vaccines link polysaccharides to a protein carrier, inducing a T cell dependent response, leading to stronger immunity.
What is the immunological mechanism of conjugate vaccines?
Polysaccharides are conjugated to a protein carrier (such as in tatanus toxoid), which enhances T cell help, leading to higher affinity antibodies, class switching and immune memory
What are important factors when designing a conjugate vaccine? (4)
Understanding pathogenesis to target the right antigen (bacteria itself or toxin)
Choosing a strong protein carrier
Ensuring T cell activation (for memory)
Avoiding hyperresponsiveness from repeated vaccinations
What are two advantages of conjugate vaccines?
More effective immune responses and protection in young infants (T cell independent responses are weak or ineffective in early life since there is no class switching when B cells are directly triggered)
What are two disadvantages of conjugate vaccines?
Expensive to manufacture
Limited strain coverage (serotype replacement may become a problem)
