immunology 3 (vaccines)

Vaccination

Introduction of a compound into the body to stimulate an immune response to a specific disease

Immunization

Process by which a person becomes protected against a disease through vaccination

Inoculation

Can mean the same as vaccination, or to introduce a micro-organism (all three terms are used interchangeably)

Passive immunization

Administration of preformed antibodies

Passive immunization – onset of protection

Immediate protection

Passive immunization – duration

Short-lived with no memory

Passive immunization – fetal protection

Does not protect the fetus

Passive immunization – shortcoming of repeated use

Repeated use can cause hypersensitivity

Examples of passive immunization

Tetanus antitoxin; antivenom for snake/spider bites

Active immunization

Administration of antigen to induce an immune response

Active immunization – onset of protection

Delayed protection

Active immunization – duration

Long term with memory

Active immunization – fetal protection

Can protect the fetus

Active immunization – hypersensitivity

Hypersensitivity is less common than with passive immunization

Examples of active immunization

Most vaccines for infectious agents

Innate immunologic memory (trained immunity)

Memory in NK cells, monocytes, and macrophages; "training" occurs with repeated exposure to pathogens; often enhanced by adjuvants

Mechanisms of innate immunologic memory

Altered PRR expression; metabolic changes; epigenetic reprogramming; altered cytokine release

Adjuvant

Chemicals, microbial components, or proteins used to enhance the immune response to antigens in a vaccine

Mechanisms of adjuvants

Enhance antigen presentation; improve antigen stability; act as immunomodulators

Adjuvant – shortcoming

Some association with adverse effects

Ideal vaccine – production and storage traits

Inexpensive to produce; consistent between batches; stable without refrigeration; long shelf life

Ideal vaccine – immune response traits

Effective; activates multiple clones of T and B cells; provides life-long immunity; no adverse side effects

Types of vaccines

Live virulent; modified live; killed/inactivated; recombinant viral vector; subunit; toxoid; naked DNA; mRNA

Live virulent vaccine

Uses fully virulent organism; uncommon; risk of causing clinical disease

Live virulent vaccine – example

Parapoxvirus (contagious ecthyma) vaccine in sheep, given by scarification of the virus on the skin

Modified live vaccine (MLV)

Most common type; pathogen is altered to reduce virulence

Methods of attenuating pathogens for MLVs

Heat; passage through cell culture; genetic engineering

Modified live vaccine – disadvantages

May revert to virulence; may cause disease if inhaled or ingested; possibility of contamination; less stable than killed vaccines (often require refrigeration); blocked by maternal antibodies; usually not recommended in pregnant females

Why are MLVs usually not recommended in pregnant females?

They contain replicating (live) organism that can cause disease or harm the fetus

Maternal antibodies and vaccination

Maternal antibodies block the response to some vaccines, especially modified live vaccines

Whole killed organism vaccine

Organism is antigenically intact but unable to replicate or cause disease; treated with chemicals such as formalin, alcohol, or alkylating agents

Whole killed vaccine – disadvantages

Require adjuvant; less effective than MLVs (more doses required); can fail to induce a T cell response

Whole killed vaccine – advantage

Unable to replicate or cause disease (more stable than MLVs)

Autologous vaccine

Custom vaccine made from organism/tumor cells isolated from a sick animal, killed, adjuvanted, and injected into the same animal

Autogenous vaccine

Custom vaccine made from organism isolated from a sick animal, killed, adjuvanted, and injected into herdmates

Autologous/autogenous vaccines – type

They are killed vaccines (isolate organism, kill, add adjuvant)

Recombinant viral vector vaccine

A benign carrier organism (e.g., canarypox) engineered to carry a gene for a protein from another pathogen

Recombinant viral vector – advantages

Induces immunity even with maternal antibodies; no adjuvant needed; cannot revert to virulence; unable to cause disease

Recombinant viral vector – disadvantage

Complex and expensive to make

Subunit vaccine

Immunogenic proteins and metabolites from the pathogen, produced by viral or bacterial cultures

Subunit vaccine – advantage and disadvantage

Economical; requires adjuvant

Toxoid vaccine

Chemically modified toxin that is no longer toxic but is still antigenic

Toxoid vaccine – mechanism of protection

Antibodies bind the toxin and prevent its interaction with the receptor

Naked DNA vaccine

Pathogen gene inserted into a bacterial plasmid, which is introduced into the host

Naked DNA vaccine – routes of delivery

Injection; transdermal; mucosal administration

Naked DNA vaccine – mechanism

Plasmids transfect host cells including APCs; gene is expressed and protein is presented on the APC surface

Naked DNA vaccine – immune response and maternal antibodies

Mixed Th1 and Th2 response; not inactivated by maternal antibodies

mRNA vaccine

Contains mRNA encoding one or more antigens that is translated by host ribosomes into proteins

Types of mRNA vaccines

Non-replicating mRNA; self-amplifying mRNA

Why are mRNA vaccines encapsulated in lipid nanoparticles?

Protection of the mRNA and promotion of cellular uptake

mRNA vaccine – advantage

Rapid production

Equine influenza vaccine – infectious EIV (live virulent)

Most uncommon; effective but dangerous

Equine influenza vaccine – modified live

Most common; reduced virulence via cell passaging and genetic engineering; blocked by maternal antibodies; not recommended for pregnant females

Equine influenza vaccine – inactivated whole virus

Unable to cause disease; requires adjuvant; can fail to induce cell-mediated immunity

Equine influenza vaccine – HA and NA subunit

Requires adjuvant; economical

Equine influenza vaccine – canarypox viral vector

No adjuvant needed; induces immunity even with maternal antibodies

Equine influenza vaccine – DNA-based

Can induce immunity even in the presence of maternal antibodies

Four categories of vaccine failure (Lyons et al. 2016)

Animal-related; vaccine-related; incorrect usage; programme problems

Most common cause of vaccine failure

Incorrect usage (failure to vaccinate properly)

Animal-related causes of vaccine failure

Immunodeficiency; suboptimal immune response; immature immune system; poor health; waning immunity; immunological interference (e.g., maternal immunity)

Vaccine-related causes of vaccine failure

Low potency; incorrect serotype; poor match to field strain of same serotype; interference from other vaccines; manufacturer problems (e.g., poor quality batch)

Incorrect usage causes of vaccine failure

Incorrect dose or route of administration; no booster vaccination; poor storage (e.g., cold chain issues); beyond expiry date of product

Programme problem causes of vaccine failure

Vaccine availability; incorrect timing (e.g., relative to high risk period); suboptimal schedules (number and timing of doses)

Vaccine failure vs. failure to vaccinate

Animal-related and vaccine-related causes = vaccine failure; incorrect usage and programme problems = failure to vaccinate

Appropriate vaccine storage

Store at the recommended temperature

Appropriate handling of freeze-dried vaccines

Reconstitute immediately before use

Mixing vaccines

Do not mix vaccines unless specified by the manufacturer

Rubbing alcohol and vaccines

Rubbing alcohol can inactivate live vaccines

Vaccine expiration

Use by the expiration date

Rate of vaccine adverse effects

1–50 in 10,000

Normal vaccine responses

Mild pain, fever, lethargy, transient immunosuppression

Type I hypersensitivity vaccine reaction – signs

Swelling of the head; hives; diarrhea; vomiting; anaphylaxis (uncommon)

Type II hypersensitivity vaccine reaction

Immune-mediated hemolytic anemia and immune-mediated thrombocytopenia (dogs)

Type III hypersensitivity vaccine reaction

Arthus reaction

Arthus reaction – signs

Hyperpigmented area at the vaccination site; local inflammation; necrosis can occur; can stay for several months after vaccination

Type IV hypersensitivity vaccine reaction

Post-injection panniculitis; vaccine-associated sarcoma

Post-injection panniculitis

Inflammation of subcutaneous adipose tissue (Type IV hypersensitivity)

Vaccine-associated sarcoma

Rare, aggressive mesenchymal tumor; genetic predisposition suspected (Type IV hypersensitivity)

Vaccine-associated sarcoma – associated injections

Rabies vaccine; FeLV vaccine; microchip; long-acting antibiotic or steroid injections