immunology lecture 18 key points
natural and active immunity
infection
artificial and active immunity
vaccine
natural and passive immunity
maternal antibodies
passive and artificial
antibody transfer
under what circumstances would you use passive immunization?
an individual with an immune deficiency
toxin/venom with an intermediate threat to life
individuals with immune-deficiencies
why wouldn't use you use passive immunization?
it doesn't activate the immune system; it's just a buffer
anti-isotypic antibodies could cause problems
if the need is prophylactic
vaccination
intentional exposure to an altered pathogen; also referred to as inoculation
immunization
the process of eliciting a state of protective immunity against a pathogen
vaccine valency
polyvalent vaccines are designed to confer protection against multiple strains of pathogen
contraindications
a specific state in which treatment, surgery, drug, vaccine shouldn't be used because it could be unsafe for a particular individual
herd immunity
when the majority of the population is immune to an infectious agent, the potential reservoirs for the pathogen are reduced. the chances of that pathogen coming contact with susceptible individual are greatly reduced
morbidity
state of illness
mortality
death
immunogenicity
the ability to provoke an immune response
efficacy
the therapeutic effectiveness of a vaccine
safety
the presence or absence of adverse events
adverse event
an unfavorable or unintended manifestation of disease that is associated with administration of the drug (vaccine)
variolation
an early method of inoculating a person against smallpox by intentionally exposing them to the virus, either by scratching pus from a smallpox sore into the skin or by blowing dried scabs into the nose
vaccination
injection of cowpox rather than smallpox
cross-reactivity
Louis Pasteur expanded the work to other infectious diseases
smallpox is the only disease to be completely eradicated, because:
it evolves slowly, antigens are conserved
the vaccine is a live virus that establishes infection at the site of injection; it mimics the innate and adaptive response
smallpox is human-specific; no reservoirs in other species
what are the three major goals of vaccination?
safety
efficacy
sustainability/achievability in target populations
in general, what correlates with immune protection?
basic research and rational design are important to advance vaccine development
vaccine development begins with basic research to discover immunogens
identification of specific immune targets or correlates of immune protection are crucial for full development
what is meant by rational vaccine design?
original strategies for vaccine production included: isolate, inactive, inject
rational design allows us to factor the genetic sequence and structure of the pathogen into the design of the vaccine
reverse vaccinology is the use of knowledge of a pathogen's physiology and how it exploits our immune system
live attenuated vaccine
the pathogen is alive, but is attenuated
grown under sub-optimal conditions; the pathogen survives and reproduces but can't cause harm
pathogenicity is lost, but immunogencitiy is retained
MMR, chickenpox, smallpox, rotavirus
what are the benefits of live attenuated vaccines?
the initial response is strong, large quantities of immunogen are made
they require relatively few booster immunizations
some are attenuated in certain species, but not in others
some can be produced by growing the pathogen in abnormal culture conditions
some can be genetically engineered
what are the drawbacks of live attenuated vaccines?
potential mutation back to virulent form
risk of some disease-related complications
requires cold-chain
recombinant DNA technology can now be used to make them safer
inactivated or killed vaccines
the whole pathogen is killed or inactived
the pathogen structure are preserved, but the pathogen cannot replicate or become virulent again
polio, hepatitis A, flu, rabies
what are the benefits of killed vaccines?
safer
more stable
they often don't require a cold-chain
what are the drawbacks of killed vaccines?
now as robust of a response
because they don't replicate, they require large quantities
because they're dead, they can't penetrate host cells, endogenous response is severely diminished
what is a toxoid vaccine?
the disease may be due to an exotoxin secretion and not due to the pathogen itself
toxoids are exotoxins that have been chemically altered such that lost their pathogenicity but retain their immunogenicity
examples include diphtheria and tetanus
what are the benefits toxoid vaccine?
neutralizing antibodies bind to the toxin and render it harmless
what are the drawbacks of toxoid immunity?
only works on those pathogens that secrete toxins
purified protein subunit vaccination
recombinant DNA technology can be used to make protein subunits
that protein can then be part of the vaccine formulation
these vaccines are often referred to as 'acellular'
examples include hepatitis B, pertussis
what are benefits purified protein subunit vaccination?
the recombinant DNA can be manipulated such that mutation can be introduced
what are the drawbacks of purified protein subunit vaccines?
the development process can alter the epitope such that immunogenicity or stability might be compromised - that might alter the type or number of neutralizing antibodies involved
like heat-killed vaccines, these cannot get into cells and therefore there is a limited cell-mediated response
purified carbohydrate subunit vaccines
made from purified polysaccharides of pathogens
examples include pneumococcus, meningococcus
what are the benefits of purified carbohydrate subunit vaccines?
easy to purify, because there are a lot of them
very few side effects
what are drawbacks of purified carbohydrate subunit vaccines?
carbohydrates do not generate T-dependent B cell responses often require a hapten conjugate
recombinant vector vaccines
genes for key antigens are inserted into attenuated virus
the virus acts a vector for the antigenic genes which are expressed by host expression machinery
examples include COVID19, HIV, RSV, Zika
what are the benefits of recombinant vector vaccines?
all the benefits of attenuated vaccines
fewer risks - not using the actual pathogen, little chance of reversion
the characteristics of the vector can be advantageous
what are the risks of recombinant vaccines?
immune responses against the vector
similar to attenuated viruses, particularly stability problems
vaccine excipient
an inactive molecule that serves as a support or aid to the drug but has no direct therapeutic impact
preservatives
adjuvants
stabilizers
cell culture materials
inactivating ingredients
antibiotics
what is an adjuvant?
molecules included to enhance the immune response to a vaccine, while limiting the amount of antigen administered
they can increase the inflammatory response
they can enhance antigen presentation
they can increase antigen stability
what are liposomes?
microscopic, spherical vesicles made of one or more phospholipid bilayers that can enclose an aqueous core
what is a booster vaccine?
booster vaccination is required to achieve protective immunity to many pathogens
what is VAERS?
vaccine adverse event reporting system
contact your healthcare provider
report an adverse event using the VAERS online form or the downloadable PDF
what are therapeutic vaccines?
treatment rather than prevention
chronic infection
allergy
chronic inflammation
coronavirus
type of virus
SARS-CoV-2
the specific virus
COVID19
the named disease cause by infection of the virus
how does coronavirus infect us?
an infected individual expels virus laden droplets which are then inhaled by a second
the inhaled virus finds its way to the upper respiratory tract where it utilizes a receptor known as angiotensin-converting enzymes 2 to enter host cellsS protein of virus attaches to ACE2
once inside it hijacks the cell's machinery
further infection results in movement down the respiratory tract
what is herd immunity
when enough people in an area have immunity to a disease that it no longer spreads easily. it usually takes a large number of people getting vaccinated against or infected with the germ to achieve herd immunity
how do mRNA vaccines work?
mRNA vaccines teach our cells how to make a protein that will trigger an immune response inside our bodies
like all vaccines, they benefit people who get vaccinated giving them protection against diseases without risking the potential serious consequences newly available to the public