Vaccines Flashcards
Disadvantages of subunit vaccines
often poorly immunogenic without adjuvants
polysaccharide antigens elicit T independent responses
What type of vaccine is
measels
live attenuated
Adjuvants
agents that enhance the immunity induced by vaccines
1) can enhance translocation of antigen to lymphoid tissues
2) provide physical protection to antigens, allowing a more prolonged exposure to the immune system
3) often provoke local immune reactions at the site of immunization, usually through interactions with innate immune receptors such as TLRs
Herd immunity
reduces the spread of disease
Classical vaccine strategies
live attenuated
inactivated
subunit
What type of vaccine is
rubella
live attenuated
What type of vaccine is
HPV
virus like particle
disadvantages of inactivated vaccines
risk of incomplete inactivation
rabies, polio, FDM inactivation failures
requires a system to grow virus
manufacture requires handling of large volumes of virulent pathogen
manufacture often expensive
inactivation may alter immunogenicity
(1960s RSV vaccine)
requires boosting
Advantages of subunit vaccines
can induce specific immune responses against molecules involved in virulence/pathogenesis
Disadvantages of virus like particles
may require multiple doses (recent data says maybe not)
induces a limited immune response (to ssurface antigens)
can be expensive to manufacture
Virus like particle vaccines
consist of viral structureal proteins that, when overexpressed, spontaneously self-assemble into particles that are indistinguishable from infectious virus.
VLPs do not contain viral nucleic acis and are, therefore, not infectious
Subunit vaccines
consists of purified components derived from pathogen
toxins
polysacchardies derived from bacterial capsule
vira surface antigens
Examples of DNA vaccines
None FDA approved
JEV in australia
Zika trials
DNA viruses
Injection of DNA coding for target molecule. The gene can be introduced using a viral vector, or can be injected as naked DNA. Once the DNA enters the cell, the target antigen is expressed at high levels. The antigen is then:
1) processed for presentation by MHC, leading to teh induction of T cell responses
and or
2) secreated, leading to the induction of Ab responses
What type of vaccine is
hep a
inactivated whole pathogen
subunit vaccines against polysaccharides
now obsolete
high IgM
low IgG
weak memory response
Consequences of immunization
circulating antibody in the serum
increased frequency of pathogen specific B and T cells (memory cells)
rapid response to infection.
Safety of various vaccine types
the less alive…
the safer
Least
live attenuated
inactivated
isolated pathogen components
recombinant proteins and VLPs
DNA
MOST
What type of vaccine is
flumist
live attenuated
Conjugate vaccines
consists of purified components of a pathogen(hapten) linked to a higly immunogenic carrier (such as inactivated bacterial toxins)
allows for a T-dependent antibody response
often referred to a hapten conjugated to a carrier
What type of vaccine is
varicella
live attenuated
What type of vaccine is
sabin polio
live attenuated
What type of vaccine is
haemophilus influenza serotype B (HIB)
conjugate vaccine
purified pollysaccharide from
Live attenuated vaccines
live pathogens that replicate in the host but do not cause diseqase because the pathogen has been mutated to a non pathogenic form
measels
varicella
sabin polio
mumps
rubella
flumist
Methods of attenuation
repeated passage in a different species
repeated passage in cell lines
repeated passage in cold
genetic reassortment with attenuated genes
deletion of mutation of genetic sequences
use of natrually occuring nonpathogenic relative
What type of vaccine is
salk polio
inactivated whole pathogen
What are vaccines
harmless agents that elicit adaptive immune response
Common adjuvants
alum
mineral oil
squalene
TLR agonists (MPL(acts on TLR4) and CpG)
Consequences of attenuation
a less fit pathogen with modified
tropism
gene expression
immunogenicity
and/or
ability to replicate
What type of vaccine is pneumococcus
conjugate
purified pollysaccharide
Recombinant DNA technology of vaccines
subunit
conjugate
virus like particles
DNA
Advantages of DNA vaccines
inexpensive to manufacture
vaccines are often highly stable
quick development time
What type of vaccine is
influenza
Inactivated whole pathogen
Benefit of T cell dependent responses (protein or protein conjugate vaccine)
Strong IgG memory response
effective in children
disadvantages of DNA vaccines
effectiveness unclear
may be more effective in generated cell-mediated immune response (for therapeutic vaccines)
safety unclear
likely require multiple doses and multiple delivery platforms
What are appropriate targets for vaccination
against viruses
B cell to make antibody: protection against infection
prophylactic
therapeutic?
Making CD8 Tcells: eradication of established infection
prophylactic?
therapeutic
Advantages of inactivated vaccines
reversion not an issue
multiple antigens present
What type of vaccine is
diptheria
subunit
Emerging trends in vaccines
1)Novel delivery systems Mucosal delivery( skin patches, microneedles, aerosol)
2) Novel adjuvants
activators of innate immunity
TLRs (CpG oligonucleotides, others)
Targeting of specific cell types (B cells, mucosal cells)
3) emerging infectious diseases
rapid production of vaccines to face emerging threats
4) non-traditional vaccine targets
self molecules involved in diseases processes
allergens
substances of abuse (ex nicotine, concaine)
Immunogenicity of the various types of vaccines
the less alive
the less immunogenic
Advantages of live attenuated vaccines
highly immunologic, stimulates a broad immune response (innate and adaptive)
all antigens are expressed (multiple targets)
usually effective with a single dose
often inexpensive to manufacture
Advantages of virus like particle vaccines
excellent safety profile
does not rely on ability to grow pathogen
highly immunogenic due to repetative structure
inside of particle can be modified with adjuvants
What are appropriate targets for vaccination
extracellular bacteria
B cells to make antibodoes
can fn in complement, neutralization, opsonization
most modern vaccines against bacteria target capsular polysaccharides
CD4+ T cells
also vaccines target bacterial toxins, and induce neutralizing antibodies
What type of vaccine is
tetanus
sunbunit
Disadvantages of live attenuated vaccines
can revert back to pathgenic form
polio virus nigeria sept 07
requires a system to grow virus
potential contamination (SV40 (can transform cells) in polio vaccine)
can be dangerous in immunodeficient or pregnant individuals
inactivated whole pathogen vaccines
preparations of normal, infectious pathogen that have been inactivated, usually by treatment of chemical agent
Salk polio
Influenza
Hep A
What type of vaccine is
meningococcus
conjugate
Vaccine reactions
immediate (within 24 hours) vs delayed (14-28 days)
generalized systemic reactions: fever, arthralgia, headache, fatugue, generalized rash
local reaction: swelling, pain, erythema
allergic: anaphylaxis, generalized urticaria (hives), dizziness, syncope, rate events and risk is minimized by screening (do you have any allergy to eggs)
trasient thrombocytopenia (eg measels; immune mediated)
rare reactions: guillain-barre syndrome, post vaccine encephalitis
vaccine adverse evente reporting system (VAERS)
national childhood vaccine injurty compensation act
What type of vaccine is
mumps
live attenuated
What are appropriate targets for vaccination
against intracellular bacteria
CTL responses probably most important
there are no particularly effective vaccines against intracellular bacteria that are currently approved clinically
What type of vaccine is
pertussis
subunit
