Vaccination

1. Vaccination Lab 14

2. Immunity Active immunity • Develops as a result of infection with a microorganism • OR administration of vaccine prepared from live or inactivated organisms, antigenic fractions or detoxified exotoxins

3. Immunity Passive immunity • Transfer of maternal antibodies to offspring or injection of antibodies • Domestic Mammals – intestinal absorption of antibodies from colostrum within 1st few hours of life • Birds – maternal antibody transferred to yolk where developing chick absorbs it • No maternally derived passive immunity in fish

4. Vaccines • Preparations of antigenic material • Administered to induce active immunity in recipient animal against a specific organism • Vaccines may be single component or mixed combined preparations • Immune response usually specific for each agent although cross protection may occur

5. Why vaccinate? • prevent/reduce severity of disease in individual • animals/herd • Limit pathogen spread within populations • reduce suffering/death in companion animals • improve welfare/reduce losses in production animals due to disease • e.g. improved growth rates, improved milk yields, improved fecundity • reduce transmission of zoonotic or food borne diseases • protection of endangered species/animal collections • aid eradication programmes e.g rinderpest & FMDV • Cost effective • Cheap • Efficient prevention • Profit for veterinarian

6. The perfect vaccine is? Safe Efficacious (induces protective immunity in all vaccinated animals) Evokes long lasting immunity Minimal requirement for boosting Stable and easy to administer Commercial considerations: - Cost, compatibility with other vaccine components, etc

7. In Practice : • Who do I vaccinate ? • mother (for passive immunity in young), susceptible • Should I vaccinate ? (Must I vaccinate?) animal health, pregnancy status, timing, risk • Which vaccine do I use ? manufacturer, efficacy, components...... • When do I administer and how often safety, boosting intervals (> annual ?) • How do I administer (and store) preparation, route, site Literature Manufacturer’s datasheet

8. Current vaccines • Inactivated vaccines • Live vaccines • Single component • Multi component • Passive protection (antisera)

9. Inactivated Vaccines • Most commonly used at present • Whole virus or bacterial cells • Known as BACTERINS if bacterial • Formaldehyde inactivated • Preserved with phenol • Mixed with adjuvant

10. Antigens preserved in inactivated vaccines • Envelope (viruses) • Fimbriae • Capsules • Outer membrane proteins • Cell wall lipopolysaccharides • Iron binding proteins • Toxins

11. Production of Inactivated Vaccines • Seed stock maintained at low passage to conserve pathogenic determinants • Grow culture to produce optimum yield of pathogenic determinants • Harvest cells or precipitate supernatant • Inactivate toxins to toxoids • Add adjuvants and preservative • Pack for distribution • Normally require more than one administration

12. Inactivated (killed) vaccines Whole Cell/Culture Kavak L, Fort Dodge, Merthiolate-killed Leptospira icterohaemorrhagiae and L. canicola for dogs Capsules Suvaxyn APP, Fort dodge, killed whole cell vaccine with capsular antigens from serotypes 3,6, and 8 of Actinobacillus pleuropneumoniae for pigs Cell membranes Stellamune, Pfizer, Mycoplasma hyopneumoniae killed culture vaccine for enzootic pneumonia in pigs Fimbriae Porcilis Porcol 5, Intervet, K88ab, K88ac (F4), K99 (F5) 987P (F6) and LT Toxoid of E. coli against piglet diarrhoea Crude culture supernatant Blackleg vaccine BP (Vet), Schering Plough, Whole culture inactivated Clostridium chauvoei With toxoids. Vaccine for cattle Iron restricted proteins Salenvac, Intervet • Contain sufficient antigen to stimulate antibody production • Generally require 2 doses in order to generate sufficient response for protection • Inactivation may modify surface antigens • Organisms are dead so won’t replicate • May be whole killed bacteria or bacterial components known as sub-units • Given by injection • Annual boosters

13. Use of Inactivated Vaccines • Intramuscular parenteral administration • Two or more injections • Elicit IgM and IgG antibodies • Poor local (mucosal) and cellular immunity • Poor duration of immunity • Passive immunity for offspring (vaccinate mum)

14. Disadvantages of killed vaccines 1. Need to ensure complete inactivation 2. Cellular components may cause side effects Rabies vaccine produced in neural tissue (Semple-type vaccines) can cause neurological problems in human beings (now superseded) FMD vaccine produced in tissue culture can cause hypersensitivity and anaphylaxis in cattle 3. More than one injection usually required 4. Cold chain required for storage and transport

15. Component Vaccines • One or more protective antigens • Toxoid, secreted antigen and/or structural proteins • Require moderate amounts of antigen • Administered with adjuvant

16. Toxoids • Toxins obtained from bacteria (supernatant, secreted) and treated by heat or chemicals (formaldehyde) • Destroys toxicity and capability of causing disease but retains immunogenicity • Stimulate the formation of toxin neutralising antibodies • Usually contain adjuvants Toxins Lambivac, Intervet, Lamb Dysentery, Struck, Pulpy kidney and tetanus vaccine for sheep, - TOXOIDS of C. perfringens Types B, C and D and C. tetani with alum and thiomersal preservative

17. Adjuvants • Inactivated vaccines contain adjuvants that enhance the immune response to the vaccine • Induce inflammation at the site of vaccination • May cause local irritation and swelling at site of vaccination • Adjuvants used are aluminium hydroxide, aluminium phosphate, alum, mineral oil such as liquid paraffin

18. Adjuvants that enhance immune responses

19. Live Vaccines • Live microorganisms that have lost ability to cause disease by treatment with: - sublethal chemicals - multiple passage on lab media - passage in cells - through a different host - heat • Non pathogenic forms of the infecting organism • Retain many or all of the surface antigens from which they are derived • Replicate in the host but cause no disease • Stimulate CMI and antibody both locally and systemically • Not genetically defined

20. Live Vaccines Bordetella bronchiseptica, Attenuated strain, INTRANASAL FOR KENNEL COUGH (Intrac, Schering Plough) Bacillus anthracis, Capsule deleted, INTRAMUSCULAR FOR CATTLE (Anthrax spore vaccine, DEFRA, Licence only) Chlamydophila abortus, Freeze dried attenuated strain 1B, intramuscular for ENZOOTIC ABORTION IN SHEEP (Tecvax Chlamydia, Vetoquinol) Salmonella enteritidis, Naturally-attenuated oral vaccine for poultry (Lohmann) Trichophyton verrucosum, Attenuated live freeze dried vaccine given intramuscularly FOR RINGWORM IN CATTLE (Ringvac Bovis LTF-130, Intervet) • Live vaccines stimulate immunity at mucosal surfaces, the entry points for most pathogens (GI tract, Respiratory tract) • Living vaccines colonise and replicate on the surface of appropriate mucosa • Immunity long lasting usually but generally less than that following natural infection • Maternal antibody and antibiotic treatment may inhibit vaccine replication

21. Disadvantages of live-attenuated vaccines 1. Possible presence of adventitious agents in the cells and medium used for growth 2. Cold chain required for storage and transport 3. Limited shelf-life 4. Reversion to virulence / side effects

22. Passive immunity • Provided by dam • Requires first administration and boost • Booster given before parturition • Egg/placental transmission in some species • Colostral antibody in most farm species • Milk antibody

23. Veterinary immunotherapy and prophylaxis • Hyperimmune polyvalent antisera used traditionally • Raised in horses • Monoclonals now available • Colostrum/immunoglobulin from other species • Given before disease/after exposure

24. Current Hyperimmune Antisera Tetanus Antitoxin Behring, (Intervet), 1000 units antitoxin/ml derived from horses and preserved using 0.5% phenol, subcutaneous or intramuscular Lambisan, (Intervet), Lamb dysentery, struck and pulpy kidney, Antiserum raised in horses to C. perfringens  and  toxoids given subcutaneously • Commercially available preparations of antisera produced by immunising horses or cattle • Sera contain the appropriate antibodies or antitoxins • Provide passive protection when unimmunised and exposed e.g. tetanus • May produce hypersensitivity in recipient of sera

25. What you need to know • How specific diseases are controlled (is vaccine used?) • Aim of vaccination • Types of vaccine • ‘Limitations’ of vaccines • Where to find detailed information as to HOW and WHEN to vaccinate

26. Vaccine development: emerging disease • Are current vaccines available for related strains: Do they protect against emerging strains ? • If new vaccine required : time lag development, safety and efficacy testing other potential limitations : availability of reagents for production (eggs : H5N1), effect of time lag re antigenicity in vaccine vs field strains, appropriate to use • Importance of hygiene/husbandry/isolation measures until vaccine developed

27. Why develop new vaccines? • induction of more effective/longer lasting immunity (in more animals) • induction of better immunity than wild type virus infection • increased safety [nonliving >living] • protection against currently circulating strains (new vaccine components/greater cross protection) • development of vaccines against new/emerging diseases • development of therapeutic vaccines

28. Safety/efficacy issues Quality control - incomplete inactivation of 'inactivated vaccine' - contamination of live vaccine with another pathogen or reversion to virulence - ineffective vaccine due to poor quality control, inappropriate storage or administration

29. Safety/efficacy issues Biological • - reaction to adjuvant • - vaccine-associated sarcomas (cats) • - autoimmune disease + ? other long-term effects • - immunosuppressed/pregnant animals and live vaccines • interference from maternally derived antibody (MDA) • variation in response to vaccination in different animals • antigenic diversity/drift in field strains

30. Summary Vaccination is major means by which viral disease is prevented Immunisation - Passive (MDA, Ig, ‘boosted’ MDA) Active (pathogen/vaccination) Non-living Living Application of molecular techniques to produce “next generation vaccines”