(20) Vaccines and Vaccination
Terms in this set (122)
What is the goal of active immunization of an individual or animal?
To elicit specific protective immunity and immunologic memory (anamnestic response)
The anamnestic response is the ____________ principle on which vaccination is based
Vaccines are almost always intended for use only on what animals?
Vaccines are most effective against what?
Poorly infectious agents whose antigens are relatively invariant
Vaccination protects against infection and eliminates or prevents the development of carrier states
Vaccination DOES NOT protect against infection NOR does it eliminate or prevent the development of carrier states
The correct use of vaccines reduces the consequence of what?
The particular infection on the animal or individual
What is not directly affected by vaccination?
The nonspecific immune system
What is variolation?
• In the eleventh century the Chinese vaccinated their children against smallpox using vesicular fluid containing live smallpox virus (Variola virus)
• Reduced case fatality rate from 25% to 1%
What is vaccination?
• (Vaccinus-pertaining to cows)
• The administration of an antigen (vaccine) to an animal or individual with the intention of stimulating a protective immune response
What is a vaccine?
A preparation of antigenic material used to induce immunity against pathogenic organisms
What is a homologous vaccine?
A vaccine made from the causative agent responsible for the disease in question
What is a heterologous vaccine?
• A vaccine from an agent other than the one responsible for the disease in question
• Such as protecting puppies against canine distemper using measles vaccine
What is a bacterin?
• Killed bacterial vaccine
• Generally less effective than viral vaccines and provide short-lived, partial immunity
What is an autogenous vaccine?
Prepared from the particular strain of pathogen causing disease in that specific group of animals
What are the general principles of vaccination?
• There must be absolute identification of the causal organism
• It must be established that an immune response can in fact protect against the disease in question
• The disease should be serious enough to justify vaccination
• The risks of vaccination should not exceed the chance of contracting the disease itself (A vaccine, even if not completely safe, should be safer than exposure to the disease)
What are the requirement for an effective vaccine?
• The vaccine must induce a humoral or CMI response directed against an antigen involved in pathogenesis
• Vaccine should be safe, with minimal and acceptable side effects
• Stability -vaccines are stable for 1 year when maintained at a temp of 4 degrees C; they can deteriorate in 2-3 days at a temp of 37 degrees C
• Be reasonably cheap and adaptable to mass vaccination
What is artificial passive immunization?
Involves the production of antibodies in one animal by active immunization, followed by the transfer of these preformed antibodies to susceptible animals to confer immediate protection
When is passive immunization routinely administered?
To animals or individuals exposed to tetanus, botulism, rabies, snake bites, black widow spider bites, etc.
What are antisera?
Where are the antisera usually produced?
In young horses by a series of immunizing inoculations
Sometimes, the recipient of artificial passive immunization may produce anti-specie antibodies to what?
The isotypic antigenic determinants of the foreign antibody
If the recipient of an artificial passive immunization produces IgG or IgM specific for the foreign antibodies, what may this result in?
Immune complex hypersensitivity
What are immune globulins of horse origin treated with to reduce their antigenicity for other species?
Pepsin to degrade the Fc regions
What is artificial active immunization?
Involves the administration of antigen to an animal so that it can respond by mounting a protective immune response
Artificial active immunization stimulates the development of what?
Effector cells and memory cells
Can nonliving vaccines can replicate
Are nonliving vaccines able to cause infectious disease
What do non-living vaccines require to induce a protective immune response?
A large antigenic dose, multiple immunizations and usually the addition of adjuvants
What is a toxoid vaccine?
Nontoxic derivative of a toxin
What is the immunity to toxigenic bacteria based on?
Circulating antibodies (antitoxins) to bacterial exotoxins
What is purified exotoxin chemically modified by?
Formaldehyde treatment so that it retains its antigenicity but losses its toxicity
What is the toxoid preparation combined with before administration?
An adjuvant (ex: aluminum hydroxide gel)
What does the vaccination with the toxoid trigger?
The production of antitoxin antibodies, which can bind to the toxin and neutralize its toxic effects
What is a subunit vaccine?
Contains only one or more of the antigens of the pathogen necessary to induce protective immunity, rather than the entire organism
What is the efficacy of a subunit vaccine highly dependent upon?
The use of an effective adjuvant
What are the advantages of a subunit vaccine?
• Reduction in risk of disease
• Reduction in abortion or allergic reaction to nonessential components of the organism
Give 2 examples of a subunit vaccine
• M protein vaccine against strangles in horses
• Subunit feline leukemia (FeLV) vaccine
What is subunit feline leukemia vaccine?
• This recombinant vaccine protects cats from feline leukemia
• The antigen is derived from the envelope glycoprotein of FeLV subgroup A, expressed in E. coli
What is a plasmid DNA vaccine?
• Plasmid DNA encoding a protein antigen involved in pathogenesis is injected directly into the muscle of the recipient
• The DNA is injected in saline solution or absorbed to microscopic gold beads and fired into muscle cells with a "gene" gun
Because the DNA-encoded proteins are synthesized in the cytosol of transfected cells, DNA vaccines elicit what?
Strong and long-lived humoral and cell-mediated (cytolytic T lymphocyte) immune responses to the antigen even when administered without adjuvants
What are the potential advantages to DNA vaccines?
• The ease of manipulating DNAs to express multiple viral and bacterial antigens
• Stability (DNA vaccines can be stored without refrigeration)
• Low cost
• Long-lasting protection
• The ability to coexpress other proteins that may enhance immune responses (ex: cytokines and co-stimulators)
What is a potential problem with plasmid DNA vaccine?
Continuous antigenic stimulus may lead to tolerance or autoimmunity
Can inactivated (killed) vaccines replicate?
Can inactivated (killed) vaccines cause infectious disease?
With inactivated (killed) vaccines, it is essential to maintain what during inactivation?
The structure of epitopes on surface antigens
In general, inactivated vaccines produce ____________ immune responses with a ____________ duration than the immune responses produced by attenuated vaccines
Why is heat inactivation not recommended?
Because heat causes extensive protein denaturation and lipid oxidation
What does chemical inactivation with formaldehyde, ethylene oxide, or beta-propiolactone result in?
Little or no change in antigenicity
what is a virulent vaccine?
• Administered by an unnatural route or at a safe age
• Ex: Ovine parapoxvirus applied to a sacrified area of the inguinal region in sheep
• Anaplasma marginale vaccine (infected blood) administered to young calves
What is an attenuated vaccine?
Consists of a naturally occurring avirulent organism or a virulent organism is grown under unusual conditions (ex: passages in cell culture or embryonated eggs, growth in embryonic tissue or at low temps) that reduces its ability to cause disease
What does the process of attenuation select?
Mutants that are better suited for growth in the abnormal culture conditions ans are therefore less capable of growth in the original host
Because attenuated vaccine organisms replicate in the host, they more closely resemble what type of infection and produce what?
Virulent infection and generally produce a stronger and more durable protective immune response than do nonliving vaccines
What is underattenuation?
Some attenuated live-virus vaccines have been associated with significant disease in some recipients
What is overattenuation?
Can result in a decline in the capacity of the organism to replicate in the host, with a corresponding loss of immunogenicity
What are temperature-sensitive mutants (Ts mutants)?
Ts mutants grow optimally at low temps, but poorly at normal body temps
What is the antigen per a dose in the attenuated and inactivated vaccines?
What is the cost of attenuated and inactivated vaccines?
What is the number of doses needed for attenuated and inactivated vaccines?
Attenuated-Usually single dose
Do attenuated and inactivated vaccines need an adjuvant?
What is the duration of immunity for attenuated and inactivated vaccines?
Inactivated-Months or years
What type of immunity does attenuated and inactivated vaccines induce?
Attenuated-Humoral and CMI
Does attenuated and inactivated vaccines cause induction of interferon?
What is the relative stability of attenuated and inactivated vaccines?
Does attenuated and inactivated vaccines cause interference?
Are attenuated and inactivated vaccines dangerous in pregnant animals?
Do attenuated and inactivated vaccines have reversion to virulence?
What are recombinant antigen vaccines?
• The gene encoding an immunogenic protein is isolated and cloned in bacterial, yeast or mammalian cells using recombinant DNA technology
• When the gene is expressed, the resultant proteins are harvested, purified and used for vaccine development
Since protein antigens are processed in endosomal vesicles, they primarily induce what?
What are recombinant vector vaccines?
• Genes encoding major antigens of pathogens may be cloned directly into attenuated viruses (ex: vaccinia virus, canarypox virus) or bacteria (ex: attenuated strain of Salmonella)
• The attenuated organism serves as a vector, replicating within the host and expressing the gene product of the pathogen
What has been successfully used to protect wild carnivores against rabies?
A vaccinia virus recombinant containing the gene for rabies virus envelope glycoprotein (G protein), administered in a bait
What are deletion mutations?
It is possible to modify the genes so that the organism becomes irreversibly attenuated
What is currently available to use against pseudorabies in pigs?
A pseudorabies vaccine in which the thymidine kinase (TK) gene has been deleted
What is TK required by to replicate in nondividing cells (ex: neurons)?
Viruses from which the TK gene has been removed are able to infect __________ cells but cannot _____________ and cause __________
What are adjuvants?
Substances that, when mixed with an antigen and injected with it, enhance the immune response to that antigen
In conventional vaccines, adjuvants are used to elicit what?
An early, strong and long-lasting immune response
Adjuvants are usually combined with what?
An adjuvant allows the use of what?
Reduced antigen concentration to achieve the desired immune response, thus reducing vaccine production costs
What is the mode of action of an adjuvant?
• The formation of a depot of antigen at the site of inoculation, resulting in slow release of antigen
• The antigenic stimulus is prolonged over a period of weeks, creating the effect of multiple, microbooster exposure
What do adjuvants stimulate?
• Antigen-presenting cells to express more co-stimulatory molecules (eg: B7) and increased production of cytokines
• Granuloma formation (because macrophages in a granuloma are activated macrophages, this mechanism also enhances TH cell activation)
What are the side effects of adjuvants?
Some adjuvants may induce severe local inflammatory reactions, resulting in abscess formation and severe granulomas
What are polyvalnt (multiple-antigen) vaccines?
• Several disease syndromes may be caused by more than one organism, thus it is now commonplace to incorporate several antigens in one vaccines
• In addition a single vaccine may contain several antigens against unrelated diseases
When different antigens in a mixture are inoculated simultaneously, what may occur?
Competition between antigens
What may the competition between antigens results in?
• Less than optimum immune response to a number of antigens (interference)
• Manufactures take this into account and modify their mixtures accordingly
Whether parenteral or local immunization is necessary for protection depends on what?
The pathogenesis of the disease
How can systemic immunity be administered?
• Subcutaneous (SC)
• Intramuscular (IM)
How can local immunity be administered?
• Oral Routes
How can mass vaccination be administered?
• Aerosolization (spray method)
• Drinking water (not tap water)
Vaccination schedules vary among the domestic species and even from area to area
What questions have to be considered when formulating a vaccination schedule?
• Is it likely that sufficient immunity to protect the animal against a given disease is already present?
• What is the nutritional status of the animal?
• What is the health status of the animal?
• Does the animal have possible immunosuppression attributable to physiologic stressors or pharmacoloic intervention?
• What is the level of exposure that the animal is likely to encounter for the disease being considered for vaccination?
Why is the nutritional status of the animal an important consideration?
Inadequate nutrition, including deficiencies of protein and certain micronutrients (ex: copper and zinc) is known to restrict immune responses
Why are animals under stress poor subjects for immunization?
Because the immune repsonse may be diminished by various mechanisms, including immunosuppression by endogenous corticosteriods
When should glucocorticoid therapy be stopped?
A week before and 2 weeks after primary vaccination
What are important factors in formulating a vaccination protocol?
• Disease prevalence
• Population density
• Exposure to other animals
Maternal antibodies inhibit the immune response of the newborn to what?
Ideally vaccination should be delayed until when?
• The titer of maternal antibody in the young animal has declined to near zero
• However this may introduce a "window of susceptibility" in the newborn
For kittens and puppies, when are a series of vaccinations given?
At 3 to 4 week intervals between 6 and 16 weeks of age
Vaccination can break through maternal antibody interference when in most puppies and kittens?
By 12 weeks of age
When can calves, lambs, kids, foals and piglets be vaccinated?
Early (3-4 months) and a second injection given about 6 months of age
Vaccination of the pregnant animal or laying hen such that high levels of maternal antibodies transferred in the colostrum and milk or in the egg, ensures that the offsprings have what?
A protective level of antibodies during the critical early days of their lives
All vaccines should be maintained at the recommended ____________ from the time they leave the manufacturer until they are administered to the animal
All vaccines should be protected against exposure to __________________
The diluent provided by the manufacturer has been ____________ adjusted for a particular organism
Practitioners should never use a ____________ intended for a different vaccine to rehydrate a lyophilized product
Because different vaccines require different ___________ values and may have various activating agents or adjuvants that can affect the ___________, practitioners should never mix vaccine products unless recommended by the manufacturer
_____________ vaccines should be used soon after they have been reconstituted
Therefore, practitioners should ensure that the vaccines are not stored for use at a later date
Why should chemically sterilized syringes not be used?
Because traces of disinfectant can inactivate attenuated vaccines
Which viral diseases do not require annual revaccinations once the animal reaches adulthood?
Viral diseases for which long-term protective immune responses are developed after vaccination (ex: canine distemper and canine parvovirus vaccines)
What does herd immunity refers to?
The immune status of population, rather than an individual animal
If a significant fraction of the population is immune to an infectious agent, the probability of a susceptible animal contacting an infected animal is what?
So low that the susceptible animal is not likely to become infected
The percentage of immune animals for herd immunity to work will vary between what?
Vaccines and on the nature of the disease, but is generally between 80 to 95%
No vaccine is 100% effective
therefore the immune response never confers 100% protection and is never equal in all members of a vaccinated population
The immune response usually follows a normal distribution pattern
What are the causes of vaccination failures?
• Apparent failure due to animal incubating disease
• Apparent failure due to poorly distributed vaccine in aerosols or feed
• Animal genetically incapable f responding to antigen
• An immune response is overwhelmed by extreme exposure to a particular pathogen
• Failure in the vaccine itself
• Failure in immune response
How is there failure in the vaccine itself?
• Death of live vaccine
• Inappropriate strain of organism or wrong organism employed
• Insufficient dose of vaccine
How is there failure in the immune response?
• Due to passive immunity (maternal antibodies)
• The animal produces a humoral response to the vaccination, but a cell-mediated response is necessary for protection
• Stress, fatigue, malnutrition, heavy parasite load (disturbances in protein metabolism)
What are the complications and side effects of vaccines?
• Virulent infectious material in vaccine
• Allergic effects
• Harmful effects on the developing fetus (abortogenic or teratogenic effects)
How can there be virulent infectious material in the vaccine?
• Incomplete inactivation in case of killed vaccines
• Some attenuated vaccines may have residual virulence
When are allergic effects observed more frequently?
With killed vaccines (multiple dosing and/or high individual doses of antigen)
What are the allergic effects in puppies?
Vaccination with whole killed leptospiral vaccine induces allergy in about 11% of puppies vaccinated (dyspnea, facial swelling, and death)
When can corneal edema (blue eye) occur?
In 1% of puppies vaccinated with modified live infectious canine hepatitis vaccine
Nonmicrobial antigens in vaccines can cause allergic reactions
(ex: egg proteins or proteins derived from tissue culture)