Vaccination PDF

Vaccination Felix N. Toka Professor, Immunology and Virology Ross University School of Veterinary Medicine Vaccination is NOT for veterinarians to make money!! Clinical Correlations The young of most of the animal species are highly susceptible to infectious diseases T...

Vaccination Felix N. Toka Professor, Immunology and Virology Ross University School of Veterinary Medicine Vaccination is NOT for veterinarians to make money!! Clinical Correlations The young of most of the animal species are highly susceptible to infectious diseases They do not have memory lymphocytes (naive T and B cells) Infectious diseases are among the leading causes of death in animals even in the developed world Immunization helps to prevent death from infectious diseases How modern vaccination begun Started by Edward Jenner in 1796 in England on smallpox Noticed that milkmaids rarely had smallpox Inferred that prior infection with cowpox virus conferred immunity to smallpox Collected pus from a lesion of cowpox in a milkmaid and injected into a boy named James Phipps Later infected James Phipps with smallpox virus The boy survived That is how the term “vaccination” was coined. vaccus - cow in Latin Essentials of useful vaccines Types of immunity Passive immunity: may be obtained by transfer of maternal antibodies to the newborn administration of the globulin fraction of serum (antiserum, or pure antibodies prepared by ethanol precipitation) maternal antibodies globulin fraction When is passive immunity necessary? During primary or secondary immunodeficiency When it is not possible for active immunity to develop and prevent disease In infections where the best immunity can only be provided by transfer of antibodies e.g., protection against tetanus in individuals not vaccinated https://wagwalking.com/horse/condition/lockjaw Lockjaw in a horse Immunoglobulinum anti febris contagiosae canis (Canine distemper)  In humans passive immunity is administered during: Botulism Diphtheria Rabies Measles Snake bites Disadvantages of Passive Immunity Probability of hypersensitivity type I or III is high Immunity wanes with time and does not lead to memory How is hyperimmune serum produced? Usually horses, goats or sheep are used for immunizations Serum is collected from these hyperimmunized animals The immunoglobulins are harvested from the serum To avoid immunogenicity from Ab, these are cleaved to Fab´2 Active immunity Acquired by: Infection with a pathogen Vaccination with, attenuted vaccines, inactivated vaccines, subunit vaccines, recombinant vaccines The primary aim of inducing active immunity is to provide long term immunity Such immunity is composed of effector T and B cells and produces memory Considerations for selecting a vaccine to induce active immunity 1. Which immune response would provide long term protection, cellular or humoral immune response? A measurable immune response does not always mean achievement of protection 2. Does the vaccine induce immunological memory? A vaccine can provide primary protection but may not leave immunological memory, and so is not protective in the long term Types of vaccines live-attenuated vaccines heat-killed/inactivated vaccines Subunit/component vaccines toxoid vaccines conjugate vaccines recombinant vaccines naked DNA vaccines vector vaccines Live-attenuated vaccines A live pathogen is used as a vaccine should be a non- or less virulent form of the pathogen is effective and induce longer lasting effect than killed vaccines Two main advantages: Replication of the pathogen increases the amount of antigen required to generate an immune response Antigenic epitopes are efficiently presented to induce both T cell and B cells for antibody production How is attenuation achieved? 1. Passaging - virulent pathogens are cultured under conditions that do not support virulence e.g., a. Canine parvovirus is cultured in insect cells leading to loss of capability to effectively infect dogs cells Such attenuated virus minimally infects dog cells If used as vaccine, will not cause disease (milder or no symptoms) but induce a protective immune response b. FluMist, the vaccine against influenza virus, was replicated under low temperature conditions (4°C-20°C) and cannot replicate at 37°C. Can only replicate in the upper respiratory tract 2. Genetic engineering (modified vaccines) By site-directed mutagenesis or removing genes responsible for virulence of a pathogens e.g., the vaccine against swine herpes virus was derived by removing the thymidine kinase responsible for replication in neurons  Killed Vaccines Are inactivated viruses, dead bacteria, or other killed pathogens that cannot cause disease Such killed or inactivated microorganisms should retain immunogenicity Heat, radiation, chemicals, and antibiotics are methods used to kill or inactivate microorganism intended for vaccine preparation Subunit or component vaccines made from purified antigens obtained from pathogens a. Toxoids - Clostridium tetani (tetnus), Corynebacterium diphtheriae (diphtheria), purified toxins are inactivated with formaldehyde, but retain immunogenicity Vaccination with a toxoid vaccine induces neutralizing antibodies Currently, genes encoding toxins are expressed in bacterial cells (e.g., E.coli) b. Bacterial polysaccharides – polysaccharides that cover the bacterial cell surface pathogenicity of certain bacteria depends on inhibition of phagocytosis by surface polysaccharides antibodies against polysaccharides can opsonize bacteria thus allowing efficient phagocytosis by neutrophils and macrophages Recombinant vaccines Genes encoding immunogenic proteins are cloned and expressed in prokaryotic or eukaryotic cells - e.g., viral proteins produced through genetic engineering. Naked DNA vaccines The approach is to identify the gene encoding the immunogenic proteins Clone the gene and insert it into a plasmid vector The plasmid DNA is then injected into the animal http://www.asmusa.org/acasrc/Colloquia/dnareprt.pdf DNA in the cell generates mRNA from which the antigenic protein can be expressed The antigen is presented by dendritic cells to lymphocytes eliciting an immune response Vector vaccines The approach is to identify the gene encoding the immunogenic proteins This gene is then cloned and inserted into a vector, mostly a virus vector The recombinant virus then serves as a vector for the inserted immunogenic protein A vaccinated host will be infected with the vector that does not cause disease but induces an immune response  DIVA vaccines (Marker vaccines) (Differentiation of Infected from Vaccinated Animals) Many infections are diagnosed by the detection of serum antibodies as evidence of exposure It permits discrimination between immune response induced by a vaccine and natural exposure Adjuvants Some antigens, alone, may not be enough to induce protective immune responses Some antigens require a substance to enhance the immunogenicity Such a substance is called an adjuvant An adjuvant is a substance that facilitates or enhances immune response to an antigen with which it is combined  The most commonly used adjuvants include liposomes microspheres immune stimulating complexes (ISCOMs) minerals (particularly aluminum salts such as alum) water-in-oil emulsions and oil-in-water emulsions agonists for PRRs (such as TLRs)  All of these act by one (or more) of three means: antigen-depot formation – slowly dissipate into intravascular tissue e.g., liposomes, alum salts antigen-carrier effects - the net-positive charge of the carrier attracts them to APCs allowing them to fuse with APCs and incorporate antigens into antigen-presentation pathways, thus enhancing immune responses e.g., liposomes, oil- in-water or water-in-oil emulsions immune stimulation – adjuvant molecules mimic PAMPs or DAMPs that bind to PRRs and activate APCs ADVERSE CONSEQUENCES OF VACCINATION Ten basic principles of vaccination 1. Vaccination is an important medical decision based on knowledge of the presence of an infectious agent in the animal herd (not every animal requires a vaccine) 2. Core vaccines are required because they protect against common, dangerous diseases. Failure to use them puts animals at risk of disease or death. Noncore vaccines are directed against disease where the risk associated with not vaccinating may be low 3. Vaccines should be administered to as many animals as possible within herd population 4. Maternal-derived (MDA) antibody will interfere with vaccines in young animals - may require a series of priming immunization and booster vaccination later 5. Immunize adult animals according to duration of immunity 6. Vaccinate pregnant animals if this procedure is supported by data sheet recommendations 7. Do not vaccinate ill animals or medically immunosuppressed 8. The decision of which vaccines should be administered is at the discretion of the veterinarian 9. Always read and understand vaccine data sheet 10. Always keep detailed records