14 - Vaccine Production Flashcards
When was the first vx’ination performed? By who? What for?
Jenner in 1796
by inoculated a healthy child w/ cowpox and exposed them to smallpox
What is active immunization?
to deliberately administer antigens to stimulate an animal to prod its own immunity (B cells and antibody prod, and T cells)
repeated exposure stimulates a secondary immune response
takes time to develop an immune response and is long lasting
What is the risk w/ and w/o vx’inating?
risk w/ - unwanted reactions, lack of efficacy/misplaced reliance on vx’ination, cost
Risk w/o vx’s - dz (Assuming vx is effective)
When should we vaccinate?
dz is common, difficult or expensive to successfully treat (often epidemic, severe, viral dz’s), dz’s that pose a human risk health (zoonotic)
Vx is efficacious
vx has low risk to use - want to stimulate adaptive immunity w/ minimal inflam
What are traditionally killed vaccines?
also known as - inactivated vx’s
live bacteria or virus is cultured and then killed w/ formaldehyde, acetone, alcohols, and alkylating agents
alternatively, toxin is cultured and activated
What are killed vaccines? What do they contain?
contains Ag’s specific to organism + Ag’s that stimulate PRR’s
tend to be less immunogenic - weaker, less complete, shorter period of immunity, very limited or no interferon production
often combined with an adjuvant*
less risk of inducing dz
What is attenuation? What are modified live vaccines?
Attenuation - modification of a pathogen so that it is less virulent - less likely to cause dz
still infects animal + capable of replicating and produces immunity
What are the advantages of MLV?
whole organism is used so they tend to stimulate a strong immunity bc they contain variety of antigens (for a more broad immunity) and may only need 1 dose for initial vx’ination. They often contain antigens that non-specifically stimulate the immune system by activating PRR’s and have no need for adjuvants
Immunity prod by natural infection, long lasting, rapid and less likely to cause allergive reaction bc of the no adjuvant
What are the disadvantages of traditional MLV?
possibility of spreading vx virus to other animals
pros - increased herd immunity
bad - spread of MLV IBR vx from calf to pregnant cow (may cause dz issues in immunocompromised/pregnant animals and cause abortion)
possibility of reversion to a virulent form - more concern w/ older MLV
if vx is contaminated, agent will not be activated (ex bovine leukosis in Australia spread by a babesiosis vx made with bovine blood)
may interfere w/ diagnostic tests - often have ana ntigen deleted to help differentiate vx from disease
How are traditional MLV made?
long term culture on an unusual medium
growth of virus in a species or tissue culture that it does not normally infect - rinderpest (a pathogen in cattle) grown in rabbits until it was no longer pathogenic to cattle. Distemper virus grown in kidney cells
Genetic manipulation - by deleting virulence factor/replication factor
alter the genetic code in some way that makes them less likely to cause severe dz
What are the 4 types of modern vaccine technology? Give a brief summary of each
- Sub-unit vx’s gene cloning - type 1 (simple/sm group of antigens amplified by gene cloning
2.Genetically attenuated organisms (traditional MLV vx’s but modified (attenuated) by genetic engineering - Live recombinant organisms - insert genome of pathogen into harmless vector that replicates within host
- Polynucleotide vx’s (COVID) - sequence viral DNA/RNA
Explain how sub-unity vx’s gene cloning works for modern live vaccines?
single/sm group of antigens amplified by gene cloning that takes known major antigens and isolates the responsible gene. It is then inserted into bacteria (like E.coli), yeast or another organism. Antigen is then prod by organism and excreted into medium or broth. Then harvested + purified
What are the advantages and disadvantages of sub-unit vaccinations
Advan - minimal risk of developing dz
disadvan - antibody response may be weak. So the protein (antigen) may not be appropriately modified or folded. No stimulation of PRRS (unless adjuvant is added), incorrect presentation of Ag to host
= some animals may NOT respond to the antigen
What is genetically attenuated organism MLV’s?
like traditional MLV vx’s but modified (attenuated) by genetic engineering
attenuation - its targeted, in multiple steps making reversion difficult, its rapid and can knock out minor antigens, use as a marker for vx’ination and a commonly used method of making MLV vaccines
What are live recombinant organims in MLV’s?
a successful method of making commercial vaccines
insert a part of the genome of a pathogen into a harmless vector that replicates within host like the canarypox or vaccinia often used as a vector
Adenovirus for COVID
and plant cells as a vector - for some vx’s to be given orally
once created, may be killed or incorporated into a vx. Live organism may be used to prod a vx - antigens belonging to pathogen are then expressed in a host