Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava ARTIFICIAL IMMUNIZATION – II The 13th lecture for the 2nd-year students May 11th, 2015 Immunization and its types I - revision •Immunization = the process leading to the development of immunity •Active immunization • natural: after infection • artificial: after vaccination •Passive immunization • natural: by the transfer of maternal antibodies through the placenta and by breast-feeding • artificial: after an injection of immunoglobulin (antiserum) Immunization and its types II – revision Immunization natural artificial active after infection after vaccination passive by transfer of antibodies through placenta and during breast-feeding after injecting antiserum (immuno-globulin) Vaccination – revision •Vaccination = administration of microbial antigens in the form of vaccines with the objective to achieve immunity •Origin of the word vaccine: • from the Latin vacca, cow • Why cow? Because Jenner in 1796 discovered the vaccination against smallpox by means of fluid from cowpox pustules • Protective antigens – revision •There is no need to use whole microbes for the vaccination •It is better when the vaccine contains only so-called protective antigens •Protective antigens = such antigens, antibodies against which protect from infection •Examples of protective antigens: • diphtheric and tetanic toxoids • capsule antigens of pneumococci etc. • surface antigen of hepatitis B virus (HBsAg) • hemagglutinin and neuraminidase of influenza A virus Types of vaccines – revision • •Toxoids (anatoxins) •Inactivated vaccines •Chemovaccines •Recombinant vaccines •Attenuated (live) vaccines Toxoids (anatoxins) – revision •Toxoid (anatoxin) = bacterial toxin free from toxicity (e.g. by the action of formalin) •Its antigens must remain identical with the original toxin •Therefore antibody (antitoxin) developed against the toxoid can neutralize the original toxin •For better effect, the toxoid has been bound to the carrier called the adjuvant, e.g. Al(OH)3 •Examples of toxoids: •tetanic toxoid •diphtheric toxoid •staphylococcal toxoid Inactivated vaccines I – revision •Bacterial v. (bacterins) – from carefully killed bacterial suspensions; in practice now only so-called: •autovaccines – from strains directly cultured from a patient – for treatment of allergic states (e.g. asthma bronchiale) •stockvaccines – prepared for stock also for other patients •Both types are successful for treatment of staphylococcal furunculosis (boils) and vaginal candidosis Inactivated vaccines II – revision •Viral vaccines – from carefully killed virions: •influenza vaccine (nowadays of the split-type from chemically disintegrated virions, with surface antigens from actually circulating strains) •Salk vaccine against poliomyelitis – in advanced countries •antirabic vaccine •vaccine against tick-borne encephalitis •hepatitis A vaccine Chemovaccines I – revision •From isolated protective antigens: •Bacterial chemovaccines: •against pertussis (acellular mixture of 3 antigens – pertussis anatoxin, filamental hemagglutinin and outer membrane protein) •against Q-fever •Viral chemovaccines: •against influenza – subunit vaccine from isolated hemagglutinin and neuraminidase Chemovaccines II – revision •Group of capsular polysaccharide vaccines: •against Haemophilus influenzae type b •against Neisseria meningitidis A and C •against pneumococcal infections (23valent) •against typhoid fever (from Vi antigen) •No cellular immunity follows (humoral only) nor immunologic memory •For infants the polysaccharide vaccines must be conjugated with a protein carrier • Recombinant vaccines – revision •Recombinant vaccines = chemovaccines made from genetically modified microbes with an inserted gene for the production of appropriate protective antigen •against hepatitis B (from yeasts with the gene for HBsAg production) •against papillomaviruses genotypes 6, 11, 16 and 18 (from yeasts with the gene for the virus surface protein) Attenuated vaccines – revision •Attenuated vaccines = live strains weakened by culturing in vitro •Bacterial: BCG-vaccine from M. bovis – against tuberculosis • vaccines against typhoid fever and cholera •Viral: Sabin vaccine against poliomyelitis • vaccine against morbilli • mumps • rubella Mixed vaccines – revision •Mixed vaccines are nowadays used most frequently •Examples: •Hexavalent vaccine against 1) diphtheria, 2) tetanus, 3) whooping cough, 4) hepatitis B, 5) invasive infections by Haemophilus influenzae type b (conjugated) and 6) polio (inactivated) •Trivalent attenuated vaccine against 1) morbilli, 2) rubella and 3) mumps Different kinds of vaccination – revision •In most countries following kinds of vaccination are recognized: a)Regular b)Special c)Extraordinary d)At injuries and accidents, at not healing wounds and before some therapeutic interventions e)Before travelling abroad f)On request • a) Regular vaccination – revision •= vaccination of every person of certain age, or of persons in higher risk of infection other then during work •It includes regular vaccination against: •Diphtheria, tetanus, whooping cough, invasive disease caused by Haemophilus influenzae type b, infectious infantile paralysis (poliomyelitis) and viral hepatitis B •Morbilli, rubella and mumps •Viral hepatitis B (e.g. of dialyzed persons a.o.) •Influenza and pneumococcal infections (e.g. persons in hospitals and old people’s homes) •Tbc as so called selective primovaccination of children from families where tbc occurs • • b) Special vaccination – revision •= vaccination of persons in the higher risk of infection during pursuance of a profession •It includes special vaccination against: •Viral hepatitis B (e.g. in laboratories with the biologic materials, in surgical departments, students of health professions) •Viral hepatitides A and B (new members of rescue service system) •Rabies (employees of respective institutions) •Influenza (workers in old people’s homes etc.) c) Extraordinary vaccination – revision •= vaccination in extraordinary situations •It includes extraordinary vaccination at: •Imminent outbreaks of e.g. • influenza • hepatitis A • meningococcus meningitis •Threat of an terrorist attack and things like that d) Vaccination at injuries etc. – revision • •= Vaccination at injuries and accidents, with not healing wounds and before some therapeutic interventions like surgery on rectum or large intestine • •It includes vaccination •against tetanus •against rabies • e) Vaccination before travelling abroad – revision •Compulsory vaccination (according to the place of stay abroad) •against yellow fever and meningococcal meningitis, possibly •revaccination against tetanus, poliomyelitis and diphtheria •Recommended vaccination against typhoid fever, cholera, Japanese encephalitis B, viral hepatitides A and B and rabies • f) Vaccination on request – revision •Vaccination on request = voluntary vaccination (paid one) •Against influenza (except specified groups of persons) • tick-borne encephalitis • papillomaviruses (except regular vaccination of 13-years old girls) • meningococci (except in outbreaks) • rotaviruses • hepatitis A (except special vaccination of • rescuers) • chickenpox • Contraindication of vaccination – revision •Vaccination = stress, but not so great as some “would-be experts” try to scare the people •During the first week after it the resistance against infection decreases •Because of this the vaccination is sometimes contraindicated but only relatively •As a rule following persons are not vaccinated: • sick • suspect from infection • reconvalescent • substantially debilitated •Caution is advisable in pregnancy • in allergic states Aim of vaccination – revision •Aim of vaccination is •not only the protection of an individual •but above all the protection of the whole population against transmission of infections •Only the high number (at least 95 %) of vaccinated persons •prevents the transmission of agents of infection on non-immune individuals and •therefore lowers the morbidity and mortality of the infection in question •… Prevention, prophylaxis and therapy of infections – I • • •Prevention of infection = avoiding an infection in the future •As the specific prevention of infection serves the vaccination Prevention, prophylaxis and therapy of infections – II • • •Prophylaxis of infection = avoiding an imminently threatening infection •For the prophylaxis, passive immunization is usually used •Only rarely for the prophylaxis the vaccination is used (e.g. rabies) or the re-vaccination (e.g. tetanus) Prevention, prophylaxis and therapy of infections – III • • •Therapy of infection • For the therapy the passive immunization is used (of course apart from antibiotics); very rarely active immunization by means of autovaccines Immunization and its types Immunization natural artificial active after infection after vaccination passive by transfer of antibodies through placenta and during breast-feeding after injecting antiserum (immuno-globulin) Artificial passive immunization •= application of antibodies in the form of antisera or globulins •Formerly: complete animal sera •Present-day preparations for passive immunization: •animal (heterogenous) sera and globulins (purified and enzymatically split) •human (homologous) immunoglobulins • – normal • – specific • Animal sera and globulins – I • •Disadvantages: •They are very antigenic • → body tries quickly to get rid of them • → therefore the protection lasts few weeks only • •Complications (even after the first application): •Serum disease •Anaphylactic shock (applying adrenalin and corticoids is essential) • Animal sera and globulins – II •Examples: •Antirabic serum (antigen used for its production = for the immunization of animals = inactivated rabies virus) •Globulin against • botulismus (antigens used for its production = botulotoxins A, B, E) • gas gangrene (antigens used for its production = α-toxins of Clostr. perfringens, Cl. novyi and Cl. septicum) • viper toxins (antigens used for its production = toxins of some European vipers, e.g. Vipera ammodytes or V. berus) • Human immunoglobulins •Two kinds of human (homologous) immunoglobulin: •Normal immunoglobulin •Specific immunoglobulins •Use: •For the prophylaxis and therapy of some infections •As a substitution of antibodies in some types of immunodeficiencies Normal immunoglobulin •Normal immunoglobulin (formerly called normal gammaglobulin) •Origin: from the mix of plasmas from at least 1000 healthy donors → hence it contains antibodies against all common infections •Examples of the use: •For the prophylaxis of hepatitis A in contacts with the ill •At the defects of antibody production •During therapy of serious infections (special intravenous preparations) Specific immunoglobulins •Origin: from the plasma of actively immunized donors: •Human tetanic immunoglobulin for the prophylaxis of tetanus •Immune antistaphylococcal plasma •Ig with high titre of antibody against HBsAg for the prophylaxis of viral hepatitis B •Ig for the prophylaxis and therapy of chickenpox and zoster •Ig for the prophylaxis and therapy of cytomegalovirus infections •Ig for the prophylaxis of tick-borne encefalitis •Ig for the prophylaxis of rabies •monoclonal Ab against RSV (in premature newborns) • • Nonspecific build-up of immunity •Replacement of missing factors: normal Ig, fresh plasma, transfer-factor from lymphocytes •Immunomodulators: components of common urinary and respiratory bacterial pathogens – e.g. peroral autovaccines, stockvaccines and a vast number of commercial preparations •Probiotics: live non-pathogenic strains of microbes reportedly able to re-establish normal mucosal microflora – e.g. strains of E. coli, Lactobacillus acidophilus, Saccharomyces boulardii •Interferon: for the treatment of hepatitis B and C and some malignancies • Recommended reading material •Paul de Kruif: Microbe Hunters •Paul de Kruif: Men against Death •Axel Munthe: The Story of San Michele •Sinclair Lewis: Arrowsmith •André Maurois: La vie de Sir Alexander Fleming •Hans Zinsser: Rats, Lice, and History •Michael Crichton: Andromeda Strain •Albert Camus: Peste •Victor Heisser: An American Doctor Odyssey •Richard Preston: The Hot Zone •Mika Waltari: The Egyptian •Richard Gordon: Doctor in the House •Richard Gordon: Doctor at Large • • •Please mail me other suggestions at: •mvotava@med.muni.cz •Thank you for your attention •