PHA 520 - L4 Vaccines and Immunosuppressants

What is a vaccine?

A preparation used as a preventive inoculation to confer immunity against a specific disease; it teaches the immune system how to fight specific pathogens, usually by exposing it to a harmless form or component of the disease agent.

What are the major types of vaccines?

Killed (inactivated), modified-live (MLV), recombinant, and mRNA vaccines.

What is a killed (inactivated) vaccine?

A vaccine containing dead microorganisms. It cannot cause infection but may produce weaker immunity than live vaccines and therefore may require boosters.

What is a modified-live virus (MLV) vaccine?

A vaccine containing a weakened (attenuated) form of the pathogen. It generally produces strong, long-lasting immunity but may pose a risk in immunocompromised patients.

What is a recombinant vaccine?

A vaccine made by using bacteria or yeast to produce a specific viral or bacterial protein; the purified protein stimulates antibody production without exposing the patient to the whole organism.

What is the major advantage of recombinant vaccine technology?

There is virtually no chance of the host becoming ill from the vaccine agent because only a specific protein is administered rather than the whole organism.

What is an mRNA vaccine?

A vaccine containing temporary mRNA instructions that cause cells to produce a harmless pathogen protein fragment, triggering antibody and memory-cell formation.

What are advantages of mRNA vaccine technology?

It contains no live, weakened, or inactivated pathogen, so it cannot cause the disease; mRNA remains in the cytoplasm and does NOT enter the nucleus or alter DNA.

What is a core vaccine?

A vaccine recommended for ALL patients because the disease is widely distributed, causes significant morbidity/mortality, and vaccination generally provides good protection.

What is a non-core vaccine?

An optional vaccine given based on an individual animal's exposure risk, geographic location, and lifestyle.

What are the core canine vaccines?

Canine parvovirus (CPV), canine distemper virus (CDV), canine adenovirus (CAV), and rabies. CPV + CDV + CAV are commonly included in DAPPV/DHPPV.

What are important canine non-core vaccines?

Parainfluenza, Bordetella bronchiseptica, canine influenza, Leptospira, Borrelia burgdorferi (Lyme), and other vaccines given according to exposure/lifestyle risk.

What are the core feline vaccines?

Feline herpesvirus-1 (FHV1), feline calicivirus (FCV), feline panleukopenia virus (FPV), and rabies. FHV1 + FCV + FPV are included in FVRCP.

What are important feline non-core vaccines?

FeLV, FIV, virulent FCV, Chlamydia felis, and Bordetella bronchiseptica; use depends on exposure/lifestyle risk. FeLV primary vaccination is recommended for kittens, with future boosters based on risk assessment.

What does “Rabies on the Right; Leukemia on the Left” mean in cats?

Rabies vaccine is administered as distally as possible in the RIGHT rear limb; FeLV vaccine is administered as distally as possible in the LEFT rear limb.

What is an immunosuppressant?

A medication that depresses the immune system by slowing or blocking immune-system functions.

What are appropriate uses of immunosuppressants?

Autoimmune/immune-mediated disease, severe inflammation, allergic conditions, certain chemotherapy protocols, and organ transplantation.

What are examples of glucocorticoid immunosuppressants?

Prednisone/prednisolone, triamcinolone, and dexamethasone.

What are common uses of glucocorticoids?

Anti-inflammatory therapy, immunosuppression, cancer chemotherapy (especially lymphoma/mast cell tumors), CNS inflammation, shock, and reduction of dangerously high blood calcium.

What are common glucocorticoid side effects?

Weight gain, alopecia, polyuria, polydipsia, and polyphagia.

What are serious adverse effects of glucocorticoids?

GI ulceration, recurrent UTIs, pancreatitis, opportunistic infections, hypertension, hypercoagulability, CHF, insulin resistance/diabetes, iatrogenic Cushing's disease with overuse, and iatrogenic Addison's disease if abruptly discontinued after chronic use.

Why must chronic glucocorticoid therapy be tapered?

Long-term glucocorticoids suppress the adrenal glands; abrupt discontinuation can cause iatrogenic hypoadrenocorticism/Addisonian crisis and may cause disease relapse.

Which species is generally more susceptible to glucocorticoid side effects: dogs or cats?

DOGS are more susceptible to steroid side effects than cats.

When should glucocorticoids be avoided (contraindications)?

Systemic fungal infections, viral infections, GI ulcers, corneal ulcers, Cushing's disease, and diabetes mellitus. Use caution with CHF and renal insufficiency/CKD.

Why should glucocorticoids NOT be combined with NSAIDs?

The combination greatly increases the risk of gastrointestinal ulceration and bleeding.

What are examples of NSAIDs that should not be combined with glucocorticoids?

Aspirin, carprofen, meloxicam, and other NSAIDs.

What is the relationship between prednisone and prednisolone?

Prednisone is converted by the liver into its active form, prednisolone.

When is prednisolone preferred over prednisone?

In CATS because cats are inefficient at converting prednisone to prednisolone; therefore prednisolone is generally the better choice.

How does dexamethasone compare with prednisone/prednisolone?

Dexamethasone is long-acting and approximately 10 times more potent than prednisone/prednisolone; it is generally used more briefly, especially during induction.

What are the major non-corticosteroid immunosuppressants emphasized in this lecture?

Azathioprine, chlorambucil, and cyclosporine.

What is chlorambucil (Leukeran)?

An alkylating immunosuppressant/chemotherapy drug that binds and damages DNA, preventing cell division; rapidly dividing cells such as lymphocytes are especially susceptible.

What is the MAIN side effect of chlorambucil?

BONE MARROW SUPPRESSION → may cause anemia and/or decreased white blood cells.

When does chlorambucil-associated bone marrow suppression commonly become evident?

Around the second week of therapy; blood testing should be performed to monitor for it.

What are major cautions/contraindications with chlorambucil?

Avoid in pregnancy and pre-existing bone marrow suppression; use caution in immunosuppressed patients or those with chronic infections. Pregnant women should not handle the drug or urine/feces from treated animals.

Why is chlorambucil particularly useful in cats?

It is relatively slow acting with fewer adverse effects than many other alkylating agents and is generally well tolerated in cats; it is often used as a steroid-sparing immunosuppressant when azathioprine would be inappropriate.

What is cyclosporine?

A non-corticosteroid immunosuppressant that interferes with helper T-lymphocyte interleukin production, preventing effective T-cell communication and activation.

What are important veterinary uses of cyclosporine?

Keratoconjunctivitis sicca (dry eye) in dogs, atopic dermatitis in dogs, IBD, feline eosinophilic granuloma complex, perianal fistulas, IMHA, feline asthma, pannus, sebaceous adenitis, and kidney transplantation in cats.

What are common cyclosporine brand names?

Atopica, Neoral, Sandimmune, and Optimmune (ophthalmic).

What is the most common side effect of cyclosporine?

GI upset: appetite loss, vomiting, and/or diarrhea.

Which oral cyclosporine formulation provides the best GI absorption?

Microemulsion formulations.

How should cyclosporine be administered to maximize absorption?

On an EMPTY STOMACH: approximately 1 hour before a meal or 2 hours after a meal.

Why may ketoconazole be given with cyclosporine?

Ketoconazole inhibits enzymes responsible for cyclosporine elimination, increasing cyclosporine blood concentrations and allowing a lower cyclosporine dose to be used.

What important precaution applies to cats receiving cyclosporine?

Cyclosporine may reactivate latent toxoplasmosis; check Toxoplasma antibody titers before use and avoid raw food/hunting during treatment.

What vaccine concern exists with cyclosporine?

Vaccines may not produce an adequate immune response, and modified-live vaccines should generally be avoided because immunosuppression theoretically increases the risk of vaccine-induced infection.

What is azathioprine (Imuran)?

A non-corticosteroid immunosuppressant that disrupts DNA and RNA synthesis, inhibiting rapidly dividing cells such as activated lymphocytes.

Why is azathioprine often combined initially with prednisone?

Azathioprine may take 1–2 months to become effective, so prednisone provides rapid disease control while waiting for azathioprine to take effect; prednisone can then be tapered.

What are examples of conditions treated with azathioprine?

IMHA, ITP, pemphigus, severe IBD, chronic active hepatitis, myasthenia gravis, systemic lupus erythematosus, and immune-mediated arthritis.

What is the major species caution with azathioprine?

Avoid or use extreme caution in CATS because their bone marrow is especially sensitive; chlorambucil is generally preferred as a steroid-sparing immunosuppressant in cats.

What are major concerns/cautions with azathioprine?

Avoid in pregnancy, breeding animals, and preferably patients with pre-existing liver disease; it can cause bone marrow toxicity and is potentially mutagenic. Wash hands after handling.

Which drug has an important interaction with azathioprine requiring a major azathioprine dose reduction?

Allopurinol.

Which other drugs can increase the risk of bone marrow problems with azathioprine?

ACE inhibitors such as enalapril and sulfa-containing antibiotics.

How should azathioprine tablets be stored?

Protected from light, preferably in a colored medication vial stored in a drawer or cabinet.