lecture 10 exam 2 Flashcards
Modified live vaccines (MLV) stimulate
B cell (MHC2 + IL2 from APC -> Th1 activation -> Bcell activation IgG production)
Th1 (MHC2 + IL2 from APC -> Th1 activation -> IFNgamma & IL2 activate CD8 -> memory)
CTL (MHC1 from APC or virus -> CD8 T cell -> memory CTL from Th1 activation)
activate CD4 Tcells to help activate macrophages, CD8Tcells and B cells
MLV vaccine risks
Brucella abortus strain 19 cuased lifelong immunity
residual virulence:
-fever, drop in milk production
-abortion of prego cows, orchitis in bulls
-undulant fever in humans
other vaccines:
- killed vaccines protect <1 yr, need adjuvant
- new live attenuated strain:
- RB51 doesnt produce LPS antigens
- stimulates strong th1
- less pathogenic than stain 19
- can be differentiated from field bacteria
reversion to virulence
north american PRRS vaccine introduced into denmark for european PRRS (60% similarity) - 1966
-vaccine virus reverted and spread within the vaccinated herds
MLV vaccines cause abortion
if vaccine given to prego cattle then increased abortion rates are seen - 2011 in wyoming and colorado
administration route influence type of response
local (intranasal, oral, vaginal) -mucosal immunity - IgA -systemic immunity - IgG systemic (subcutaneous, intradermal, intramuscular) -draining -lymph nodes - IgG -stimulates ONLY systemic immunity
poliovirus vaccine - inducing systemic and mucosal immunity
salk vaccine - killed
-given IM or SQ
-induces antibodies in blood and prevents paralytic syndrome
sabin vaccine - MLV
-sugar cube given orally
-stimulates mucosal IgA and prevents poliovirus infection at the intestine - w risk of paralytic poliomyelitis
IgE reactivity to vaccine stabilizers
immediate allergic reactions after vaccination
-severe rxns: dyspnea, facial edema, vomiting, circulatory collapse
biologics in vaccines
-IgE reactivity to fetal calf serum in 7/10 dogs
-bovine serum albumin is >1mg/dose in canine vaccines
-WHO dictates <50ng of BSA/dose in human vaccines
-IgE reactivity to gelatin and casein used in vaccines as stabilizers
recombinant vaccines
type 1: subunit vaccine
type 2: gene deleted
type 3: live vectored vaccines
type 4: DNA vaccine
type 1 recombinant vaccine
subunit vaccine
purified protein from recombinant organisms (E coli)
stimulates Th2
adv: safe, nonreplicating, isolate protective antigen
dis: present limited number of epitopes to immune system, require repeated administration and adjuvants, post translational modification of protein may not mimic naive protein (Ecoli doesnt have golgi)
rLyme
type 2 recombinant vaccine
gene deleted
live replicating organisms contain gene deletions
rPseudorabies virus
type 3 recombinant vaccine
replicating vectors
adenoviruses, canarypox, vaccinia virus, salmonella
contain hereologous genes
adv: safe, accomodate large foreign genes, infect host cells but dont replicate, express vaccine antigen in host cells, stimulates both B and T cell response, can be administered orally (stimulate mucosal immunity), no interference w maternal antibodies
dis: virulence (can actually infect w virus in immunocompromised hosts - vaccinia virus), immunity to vector may reduce effectiveness (more encounter less potent)
rFeLC (caranypox)
rFeline rabies (caranypox)
rFerret distemper (caranypox)
rEquine west nile & influenza (caranypox)
rCanine distemper virus (caranypox)
raboral V-RG (canine, wildlife - vaccinia virus)
type 4 recombinnat vaccine
DNA vaccine
naked DNA that is expressed into protien of interest
west nile virus innovator vaccine (horses) infectious hematopoiesis necrosis virus (salmon - apexIHN, novartis) DNA melanoma (dogs)
adv: safe, do not require cold chain, will be processed in host cells and proteins expressed by host cells, stimulated B and T cell responses, can add cytokines or CpGs, can be administered orally (stimulates mucosal immunity), no interference w maternal antibodies
dis: not very effective (1. prime boost strategy 2. DNA followed by killed antigens), possible integration of DNA into host genome and activate oncogenes
subunit vaccines (type 1)
consists of fragment of microbial pathogen expressed using recombinant DNA technology in host cell
recombinant antigen is formulated in adjuvant
ex: FLV - first commercially avaliable subunit vaccine
hepatitis B - composed of virus surface proteins produced in yeast
human papillomavirs - composed of the major capsid protein
live vector replicating vectors (type 3)
DNA encoding protein of interest is inserted into a live vector
RNA virus w reverse transcriptase + cDNA + virus w vaccine of interest recombines together and inserts into host cell and viral antigen expressed on target cell surface to signal an immune response
RABIES
recombinnat canine distemper vaccine
DNA vaccines (type 4)
recombinant plasmid DNA engineered to express a gene encoding an antigen
cloned microbial DNA in plasmid -> immature DC or transfected cell -> mature DC1 or DC 2 or apoptosis and immune response!
apoptosis releases virus antigen products to be processed
mRNA recognized by TLR3, 7 8 and provides natural antibodies - inflammation reaction and cause toxicity
canine and feline core vaccines
must have protects against dangerous dz: failure to use places an animal at risk -parvovirus for dogs & cats -distemper (d) -adenovirus 2 (d) -calicivirus (c) -herpes (rhinotracheitis) (c) -rabies (d & c)
noncore vaccines
against rare dz, mild dz or untested vaccines or of geographical risk
- lyme
- giardia
- canine adenovirus 1
- coronavirus
- leptospirosis
- parainfluenza
- influenza
AAEP vaccines (annual)
CORE: -tetanus -Eastern/western equine encephalomyelitis -West nile virus -rabies at RISK: -equine herpes virus 1 and 2 -equine influenza virus
duration of immunity (DOI)
rabies - 3 yr titers for feline panleukopenia - 7 yrs canine distemper - 5-7 yrs monitor vaccine titers in older animals -to make decisions about revaccination -AAHA/AAFP guidlines (core vaccine DOI is > 3yrs)
licesnsing of vaccine products
requirements of a vaccine prior to licensure by USDA
- purity (free of extraneous microorganism)
- safety (free of causing local/systemic rxns)
- potency (relative strength)
- efficacy (effective according to the indication on the label demonstrated by statistically valid host animal vaccination-challenge studies)
- relevance (product clinically relevant)
causes of vaccine pailure
incorrect administration animal fails to respond vaccine given too late - animal already infected wrong strain or organism use nonprotective antigen used
BIG TABLE
