Viral vaccines III Flashcards
What are the potential negative effects of vaccination? (6)
- Injection safety/waste disposal
- Local/systemic adverse effect
- Predisposition enhanced disease
- Predisposition auto-immune disease
- Negative effect at population levels
- Negative attitudes/perceptions
What is the difference between variolation and vaccination?
Variolation: intentional infection with pathogen
Vaccination: biological preparation to improve immunity -> much milder infection
Considering injection safety, the transmission of which viruses should be taken into account? (3)
- HBV
- HCV
- HIV
Why do we have problems associated with injection safety? (5)
- Lack of knowledge of injections
- False belief that injections are more effective than oral medications
- Healthcare workers may think patients want an injection
- Patients may demand injections,
- Clinicians make more money if they give an injection
What are examples of practices that harm the recipient of infections? (6)
- Keeping freeze-dried vaccine more than 6h after reconstitution
- Mixing two partially opened vials of vaccine
- Storing mediation and vaccine in same refrigerator
- Applying pressure to bleeding sites with used material or finger
- Use of unsterile needles/syringes
- Re-using needles/syringes
What are examples of practices that harm the health workers? (4)
- Re-using needles/syringes
- Carrying needles/placing them on a surface prior to disposal
- Recapping needles
- Reaching into container of used needles/syringes
True or false: any vaccine can cause adverse effects
True
What are examples of mild adverse events after vaccination? (6)
- Local redness
- Swelling
- Pain
- Headache
- Fever
- Nausea
What are examples of severe adverse events after vaccination? (2)
- Life-threatening allergic reactions/seizures
- Systemic disease
What is a reversion risk associated with local- and systemic adverse effects?
Reversion of attenuated viruses to WT phenotype
What is meant with ‘predisposition for enhanced disease’?
No disease after vaccination, but more severe disease when person encounters pathogen again
What are two known examples of predisposition for enhanced disease?
- FI-RSV
- FI-MV
What are the clinical signs of FI-RSV-mediated disease enhancement? (3)
- Febrile pneumonia illness
- Bronchiolitis
- Pulmonary infiltrates
Describe the correlation pattern of disease severity with age
Inverse correlation
What is FI-MV-mediated disease enhancement? When does it occur?
Atypical measles syndrome -> several years after vaccination
What are the clinical signs of FI-MV? (3)
- High fever
- Petechial rash
- Pneumonia
What is the main immunological reason for FI-MV-mediated disease enhancement?
The way the immune system perceives inactivated vaccines -> good in inducing antibodies/CD4 -> barely CD8
What are the mechanism of FI-RSV disease enhancement? (5)
- Skewing of cellular immune response towards Th2
- Low avidity antibody-mediated complement fixing immune complexes
- Antibody-dependent enhancement of viral replication
- Highly glycosylated G protein
- Lack of CTL priming
FI-RSV: How is skewing of the cellular immune response towards Th2 ensured?
Adjuvant (aluminum) promotes Th2 response
FI-RSV: what causes the lack of CTL priming?
Th2 response works against mounting a proper CTL response
What are the mechanism of FI-MV disease enhancement? (4)
- Lack of functional F-specific antibodies
- Low avidity antibody-mediated complement fixing immune complexes
- Skewing of cellular immune response towards Th2
- Lack of CTL priming
What is Dengvaxia?
Yellow fever-based dengue virus
What type of vaccinees have an increased risk of disease enhancement upon dengvaxia vaccination?
Seronegative vaccinees
Which auto-immune disease can be caused by vaccination?
GBS
Which vaccine is known to have induced several cases of GBS?
H1N1 vaccination
Which disease occurred due to the parental inactivated influenza vaccine?
Bell’s palsy
True or false: it is very hard to link vaccination to the onset of autoimmune disease
True
Which subset of patients are especially at risk after Rubella vaccination?
Pregnant woman -> risk of congenital rubella syndrome (CRS)
What is the consequence of a high rubella vaccination coverage?
No outbreaks
What is the consequence of a low rubella vaccination coverage?
Longer time intervals between outbreaks
What are the consequences of longer time intervals between Rubella virus outbreaks? (2)
- Higher mean age of patients
- Increased risk of CRS
What are the complaints when you have Evans’ syndrome?
Intracranial bleeding with thrombocytopenia
What is the BCG vaccine?
Vaccine against tuberculosis
How did the BCG vaccine lost its virulence in humans?
Being specially cultured in an artificial medium
True or false: BCG vaccination depends on the geographical area
True
Why is studying safety and efficacy of vaccines in people with immunodeficiency mainly difficult?
Heterogeneous population, diseases, and vaccines
What are other limitations when studying safety and efficacy of vaccines in people with immunodeficiency? (2)
- Published studies limited
- Often ‘eminence’ based medicine
What is meant with the vaccination paradox?
The ones that you want to vaccinate the most, are the hardest to protect
What is the main challenge associated with the vaccination paradox?
Mechanisms that render patients susceptible to infection also compromise the efficacy of vaccination
Which types of immunocompromised patients exist in the context of vaccination? (4)
- Compromised barrier function
- PID patients
- Loss of humoral immunity, not PID
- Compromised cellular immunity, not PID
Patients with a compromised barrier function mostly suffer from which type of infections?
GI infections
If patients with compromised barrier function travel to the tropics, which vaccination do you give them and why?
Yellow fever vaccination to prevent salmonella infection
How can patients acquire a compromised barrier function? (3)
- Antacids
- IBD
- Severe skin disease
Which vaccines can you not give to PID patients with a severe B- or T cell problem?
Live-attenuated vaccines
Which vaccines can you NOT give to PID patients with a B-lymphocyte deficiency? (severe/less severe)
Severe (XLA/CVID): No (live) attenuated
Less severe: (IgA/IgG def): no OPV (others safe)
Which vaccines can you NOT give to PID patients with a T-lymphocyte deficiency?
Depending on degree, all vaccines ineffective
Which vaccines can you give to PID patients with insufficient complement function? Which vaccines are highly recommended for this type of patients?
All vaccines save -> polysaccharide vaccines highly recommended
Which PID patients do you really want to vaccinate, and why?
Patients with a lack of complement function -> especially prone to infection
Which vaccines can you (not) give to PID patients with a loss of phagocytic function? Which vaccines are probably safe?
- No bacterial vaccines
- Live-attuenated vaccines probably safe
How can a patient acquire a loss of humoral immunity (not PID)?
Anti-CD20 (retuximab)
What is the consequence of loss of humoral immunity (not PID)? Leading to? (2)
Nephrotic syndrome:
1. Lose IG and B cells
2. T cell function intact
Which vaccine can you NOT give to patients that have a loss of humoral immunity (not PID)?
Live-attenuated vaccines
How can patients acquire compromised cellular immunity (not PID)? (9)
- Cortico’s
- Ciclosporines
- Tacrolimus
- Azathioprine
- Biologicals
- Chemo
- Radiotherapy
- Malignancies
- HIV
Which vaccines can you NOT give to patients with compromised cellular immunity (not PID)?
Live-attenuated vaccine
What were the results after administering COVID vaccines to people with inborn errors in their immune system? (3)
- Problem in immune system
- Most still had titers
- T cell responses similar to controls
Which auto-immune diseases may become aggravated after viral infections? (3)
- Crohn
- MS
- AID
Why do the benefits outweigh the risks when vaccinating people with auto-immune diseases against covid/influenza?
Getting the real disease is worse
What are the main conclusions when considering vaccination of immunocompromised patients? (4)
- Highly divergent group
- They can be vaccinated
- Complications can occur, but not often
- Check titers!
Why are bacterial vaccins important? (5)
- Disease prevention
- Eradication and control of disease
- Protection of vulnerable populations
- Global health equity
- Prevents AMR
When is a vaccine effective? (5)
- Safe
- (Sustained) Protection
- Induces neutralizing antibodies
- Induced protective T cells
- Practical considerations
Why is the induction of neutralizing antibodies by bacterial vaccines important?
Some pathogens infect cells that can’t be replaced -> neutralizing antibodies prevent infection of such cells
Why is the induction of protective T cell responses by bacterial vaccines important?
Some pathogens (intracellular) are more effectively dealt with by cell-mediated responses
Name possible bacterial targets that you can use for a bacterial vaccine? (5)
- Exotoxins
- Outer membrane protein
- LPS
- Flagella
- Bacterial DNA
Which types of bacterial vaccines exist? (5)
- Toxoid vaccines
- Live-attenuated vaccine
- Inactivated vaccines
- Subunit vaccines
- Conjugate vaccines
What is the main component of toxoid vaccines? What does this compound induce?
Chemically- or heat inactivated toxins -> induce neutralizing antibodies
For which diseases can you give a toxoid vaccine? (2)
- Diptheria
- Tetanus
What are the advantages of a toxoid vaccine? (2)
- Highly effective
- Safe and well tolerated
What is the main disadvantage of toxoid vaccines?
Slow manufacturing process -> culturing and manufacturing
Whooping cough is caused by which type of bacteria?
Gram-negative bacteria
Which types of bacterial vaccines are used for whooping cough? (2)
- Whole cell vaccine
- Acellular vaccine
What are the advantages of inactivated vaccines (bacterial)? (4)
- Stable
- Cannot revert to virulent form
- Safe to give to immunocompromised
- Relatively inexpensive, mass production
What are the disadvantages of inactivated vaccines (bacterial)? (2)
- Less robust immune response
- Slow manufacturing process
What are examples of inactivated bacterial vaccines? (3)
- Typhoid vaccine
- Cholera vaccine
- Plague vaccine
What do bacterial subunit vaccines contain?
One or more component(s) of bacteria (antigens)
Which components can be part of a bacterial subunit vaccine? (3)
- Proteins
- Peptides
- Polysaccharides
What are the advantages of a bacterial subunit vaccine? (2)
- Generally seen as the safest type of vaccine
- No risk of recombination
What are the disadvantages of a subunit vaccine? (4)
- Lower immunogenicity
- Usually presence of an adjuvant necessary
- Complex to develop
- Polysaccharides are a thymus-independent antigen
What is the mechanism behind bacterial polysaccharide vaccines? (2)
- Induction T cell independent response
- Direct stimulation of immunoglobulins
Why do polysaccharide vaccine not work in children?
Polysaccharides induce a T cell independent response -> B cells are not fully developed in children
What is the main principle of a conjugate vaccine?
Weak antigen (polysaccharide) covalently bound to strong antigen (protein)
What is an example of a bacterial conjugate vaccine?
HiB conjugated to meningococcal protein
Which type of immune cells are specific for the different structure of a conjugate vaccine?
- T cell -> protein “head”
- B cell -> sugar structure
How does a conjugate vaccine induce an immune response? (2)
- Strong antigen is internalized, processed and presented on HLAII to CD4+ T cells
- B cells internalize weak antigen
Which immune responses are mounted upon conjugate vaccine vaccination? (3)
- Plasma cell formation
- T cell response
- Memory B cell formation
What are the advantages of a conjugate vaccine? (3)
- Enhanced immunogenicity
- Protection of young infants
- More effective immune responses
What are the disadvantages of a conjugate vaccine? (3)
- Expensive
- Resource-intensive
- Limited strain coverage
What are the advantages of bacterial live-attenuated vaccines? (2)
- Potency > inactivated vaccines
- Immune response lasts longer
What are the disadvantages of a bacterial live-attenuated vaccine? (3)
- Risk of reversion to WT
- Not for immunocompromised
- Careful storage/transportation
