vaccines

what is the goal of vaccination?

1. prevent infection

2. prevent disease

3. decrease severity of disease

4. eradicate the pathogen

what kind of immunity do vaccines induce?

adaptive immunity

what do vaccines contain?

antigen or nucleic acid that code fro protein antigen (DNA or mRNA)

what type of pathogens are targeted by the humoral immune response?

extracellular pathogens

what type of pathogens are targeted by the cell-mediated immune response?

intracellular response

what type of response is typical to a modified live virus vaccine?

cell-mediated immune response

what is the typical immune response to a killed vaccine?

adaptive humoral immune response

what is the process to a modified live virus vaccine?

1. infected host cells present peptides to CTLs

2. more weakened virus made and infects more host cells

3. activated Th-cells make cytokines to help CTLs become activated

what are the types of vaccines?

1. toxoid

2. inactivated

3. live attenuated

4. subunit

what is the composition of toxoid?

inactivated toxin used as a vaccine

what are examples of toxoid vaccines?

1. tetanus 2. rattlesnake venom

what is the composition of inactivated vaccines?

whole killed organism

what is the composition of live attenuated vaccines?

whole live organism

what are the two type of subunit vaccines?

1. protein subunit

2. DNA or RNA based subunit

what does a protein subunit vaccine mean?

we have taken proteins from pathogen of interest to use as vaccine

what does it mean to have a DNA or RNA-based subunit vaccine?

have taken components that code for the protein of the microbe of interest

what are DNA or RNA-subunit vaccines often used for?

delivery system into RNA/DNA or host to code for protein antigen against infectious agent

what is the principle of toxoid vaccines?

the immunized host's immune system will see the toxoid (a protein) as foreign and generate an immune response to it

what are virus-like particles?

contains viral proteins that mimic the structure of the virus but do not contain genetic material

what type of DNA is injected when using nucleic-acid based subunit vaccines?

naked DNA injected

in the US what does the USDA regulate (in regards to vaccines)?

regulates veterinary biologics, NOT DRUGS

what are examples of routes of administration of vaccines?

1. IM

2. SQ

3. intranasal

4. oral

what does adjuvants mean in reference to vaccines?

substances added other than the antigen to the vaccine that maximize the effectiveness

what vaccines will we often see adjuvants added?

vaccines containing killed whole organisms or highly purified antigens

what are examples of what adjuvants can do?

1. increase immunogenecity of weak antigens

2. increase speed and duration of immune response

3. strengthen immune response

4. increase antigen affinity with antibody

5. increase mucosal immunity

what do we need to know about adjuvants?

some adjuvants cause problems in the host

how are killed vaccines inactivated?

chemicals, heat, or radiation

what are the pros of killed vaccines?

1. safer and more stable

2. easy storage

3. can be given to immunocompromised animals

why are killed vaccines considered safer than live vaccines?

they can't mutate back to virulence and infect host cells

what is the dominant response to a killed vaccine?

Th-2 dominated response to stimulate antibody (humoral response)

what are the cons of killed vaccines?

1. require adjuvants

2. stimulate weaker immune response compared to live vaccines

3. inactivation may destroy antigen epitopes

4. sometimes type-3 hypersensitivity

what are examples of problems associated with vaccine adjuvants?

1. feline sarcomas

2. type-3 hypersensitivities

what is the composition of live attenuated vaccines and why?

modified virus of intracellular bacterium because we want organism to infect and replicate inside host cells to illicit a strong cellular and antibody response

what is another name for live attenuated vaccine?

modified live vaccines

what happens when the vaccine virus infects host cells and replicates?

host cell presents viral peptides to CTLs and activated CTLs kill infected cells

what are veterinary examples of live attenuated vaccines?

1. brucella abortus

2. canine distemper

what are the pros of live attenuated vaccines?

1. many epitopes generated because presented whole organism

2. good CMI and humoral response

3. confers life long immunity

4. no adjuvant needed

what are the cons of live attenuated vaccines?

1. vaccine may cause disease (residual virulence) and or persistent infection

2. post risk to fetus if given to pregnant animal

3. risk to vet if accidentally injected

4. risk to immunocompromised

what is the name of the vaccine we use to protect cattle against brucella abortus?

RB51

what type of vaccine will result in the most robust cell-mediated immune response?

modified live vaccine

what do B. abortus field strain and vaccine strains potentially cause in cows and bulls?

cows=abortion ; bulls = orchitis

what type of pathogen is the B. abortus field strain?

intracellular bacterium; will need a good cell-mediated immunity for prevention and control = modified live vaccine

what animals can we not in general give MLVs to?

pregnant animals

examples of transmission of B. abortus to humans

1. contaminated environment

2. unpasteurized milk

3. vet doing post-mortem on aborted fetus

4. vet accidentally innoculating themselves

what is important if vaccination is part of a disease eradication program?

need to differentiate vaccinated animals from naturally exposed (field strain) animals, especially in surveillance programs

what does DIVA stand for?

differentiating infected from vaccinated animals

what is important to understand about DIVA vaccine?

does not refer to a type of vaccine

RB51 is an example of a

DIVA vaccine

what do we need to do with DIVA?

develop a test to detect antibody to the field strain that will not detect antibody to the vaccine strain

what does the RB51 strain lack?

antigens used in the test for exposure to field strain

what do surveillance tests detect in regards to B. abortus?

antibody to antigens not expressed by the RB51 strain but are expressed by the field strain (LPS molecules)

subunit vaccine

do not contain the whole pathogenic microbe

what is injected in a subunit vaccine?

1. proteins of microbe

2. DNA that codes for microbial proteins

3. mRNA that codes for microbial proteins

4. virus like particles arranges as proteins to look like virus

what does it mean when we say some subunit vaccines are "recombinant vectored vaccines"?

the live microbe is the delivery system for the DNA or mRNA it is not the pathogen itself

what are the different methods for creating subunit vaccines?

1. non-genetic engineering method

2. genetically engineered subunit vaccines

what is key when developing a subunit vaccine?

1. identify immunogenic microbial proteins

2. identify genes that coded for immunogenic properties

why would adjuvants be useful in vaccines that inject protein antigens?

proteins can be degraded quickly and adjuvant can enhance stability of the protein

what is important to understand about the vector delivery system for recombinant subunit vaccines?

the vector itself is not the pathogen, it is introducing the virus or pathogen

what are the different types of vectors for recombinant subunit vaccines?

1. vector infects cells

2. replicating vectors

3. non-replicating vectors

4. harmless, living virus or bacterium

vaccinia virus

contains gene that codes fro G protein and we inject this complex into the vector for rabies oral vaccine

Can the Canarypox-Vectored Rabies Vaccine for cats cause rabies in cats?

no; it only contains the gene for one rabies protein

what are the potential disadvantages of DNA vaccines?

1. DNA might integrate into the host genome and cause damage

what is a safer alternative to DNA vaccines and why?

mRNA vaccines because mRNA will only enter the cytoplasm of the host cell to produce the microbial protein opposed to needing to enter the nucleus like DNA vaccines

what type of immune response is generated by mRNA vaccines?

both humoral and CMI response generated

what are the challenges to mRNA vaccines?

extremely unstable requiring specific low temperature storgage

nanotechnology

embedded mRNA into lipid nanoparticles to delay degradation of the mRNA and faciliated entry into cells of host

recombinant

using enzymes to manipulate and isolate DNA segments of interest

what vaccines are a result of recombinant technology?

1. all DNA and mRNA vaccines

2. all vectored vaccines

3. some protein vaccines

duration of immunity

the length of time a vaccine establishes a protective immune response against a disease following exposure to pathogen

what factors duration of immunity depend on?

1. host factors

2. vaccine factors

3. administration factors

how is duration of immunity determined?

empirically by the manufacturer

side effect

a common but mild consequence after vaccination

what are examples of vaccine side effects?

1. mild fever

2. discomfort or pain at injection site

3. decreased appetite and activity

adverse reaction

a more serious but uncommon occurrence

when is there a high level of concern for eradication of a virus?

1. zoonotic potential

2. economic impact

3. mortality rate

4. food security

what characteristics of viruses might enhance their vulnerability to eradication?

1. host species

2. reservoir host in wildlife

3. persistent infection occurs

4. subclinical cases occur

5. number of serotypes

6. infectivity during prodromal stage

7. vaccine

8. early containment of outbreak possible

9. high level of public concern

what does a vaccination program depend on?

1. characteristics of vaccine

2. epidemiology of virus

herd immunity

vaccination of a large number of people within a given area at the same time; interrupts transmission in a population, so that those who are susceptible never encounter the infectious agents concerned.

multiagent vaccines

ensure that there will be a proper immune response to all pathogens included and no interference among them

who chooses the vaccine appropriate in a situation?

veterinarian

who chooses the route of administration for a vaccine?

manufacturer

who chooses the frequency of a vaccine

manufacturer

what is the order for the ideal type of vaccine to give if possible?

1. live attenuated vaccine

2. recombinant live virus

vaccine

primes the immune system against a specific antigen

booster

expands (clonal expansion) or reactivates (memory cells) existing immune cells to that antigen to ensure continuous protection

why are puppies and kittens vaccination schedule different different than adults?

maternal antibodies neutralize vaccine so young will not have stimulation of adaptive immune system; give more booster to ensure stimulation in case first vaccination it was neutralized

core vaccine

vaccines recommended for all animals in that species not matter their lifestyle, unless their is a specific medical reason not to vaccinate

non-core vaccine

recommended for some animals based on lifestyle, geographic location, and risk of exposure

risk assessment is determined by

1. likelihood of exposure

2. risk of unprotected exposure

when looking at a vaccine what do we ask if it is an efficacy issue?

does this situation impede the vaccine from doing its job

when looking at a vaccine what do we ask if it is a safety issue?

does this situation cause any danger or pain to that animal or its offspring

what route of vaccine administration will stimulate mucosal immune response?

intranasal, aerosolized, oral

what route of vaccine administration will stimulate systemic (parenteral) immune response

SQ, IM, and IV

why is a vaccine trial not considered finished when it enters the population?

the population will report rare adverse effects which will alter the safety