Immunization and Vaccines 1&2 Lectures 29 and 30 PDF

Immunization and Vaccines 1&2 Lectures 29 and 30 Glenn Patriquin MD  Immunization This is the use of a specific immune response to prevent or lessen the severity of disease resulting from infection or the products of an infection (e.g. toxins). We take...

Immunization and Vaccines 1&2 Lectures 29 and 30 Glenn Patriquin MD  Immunization This is the use of a specific immune response to prevent or lessen the severity of disease resulting from infection or the products of an infection (e.g. toxins). We take advantage of the ability of the adaptive immunity to form specific long- lasting responses.  Objectives of Immunization Individual protection from infection – May be for the general population or specific risk groups When a sufficient number of people are immune, infecting agents can not circulate in a population – “Herd immunity” protects those people who remain susceptible Immunocompromised, unable to be immunized etc Elimination of Infecting organism may be possible  Action of Antibodies May bind to an antigen and block its biological activity – “neutralizing antibody” – e.g. viruses or toxins which are then called “neutralized”. Coat a bacterium and make it more easily phagocytosed by an immune cell – “opsonization” improves clearance of organisms Bind to an organism and activate complement to cause lysis, and recruit immune cells to the area Immunological Memory: B Cells Antibodies are produced by B lymphocytes that are activated to become Plasma cells Each one produces an antibody that is specific for its target. When stimulated by an infection or vaccine the specific B cell clone multiplies Some of these cells become B memory cells and are long lived to allow a rapid response to subsequent exposure Immunological Memory: T Cells Specific T lymphocytes also survive as memory T cells and remain to regulate the immune response – These are also long lived cells in the lymphoid tissue – On re-exposure to the antigen they will multiply and shorten the time to a response – T lymphocytes regulate the immune response and cytotoxic T cells kill infected cells  Passive Immunization The host receives antibody produced by another host. This protection is short lived (2-3 months) and no long term protection is generated. Examples: IVIG (polyclonal), Hepatitis B Ig (HBIG), Varicella Zoster Ig (VZIG), Rabies Ig, RSV  Passive Immunization: how and why? Naturally occurring: the neonate receives antibody transplacentally from the mother, or in colostrum. Therapeutic: Antibody (immunoglobulin or Ig) is given: – To provide rapid protection after a potential exposure to an agent, e.g. after a needle stick. – To lessen the severity of ongoing disease, e.g. antibody given in necrotizing fasciitis. – For individuals unable to produce antibody.  Active Immunization (= vaccination) The generation of immunity by administering an antigen to elicit an immune response in the host. Among the first types of Jenner’s administration of cowpox virus (vaccinia) to prevent smallpox. Types of Active Immunization can be divided into: – Live attenuated (MMRV) – Virus vectors, replicating/ non replicating – Inactivated whole cell, subunit, virus like particles – DNA, RNA (COVID-19 mRNA vaccine!) – Toxoid  BCG Live vaccine Attenuated These use organisms which are limited in their ability to cause disease but share antigenicity with the virulent forms. Attenuated organisms are those that have been repeatedly cultured in the lab until they have lost their virulence properties. Administration need not be by injection, and may mimic the natural route of infection. They have the advantage that they mimic a natural infection and give stronger and long term immunity, and may not need booster doses. Live Attenuated: Disadvantages The principle disadvantages are – They may be virulent for immunosuppressed people or in pregnancy. – They may revert to the virulent form during the infection in the host. – They must be handled properly to maintain viability until they are used (need refrigeration). Harder to transport and store  Live Attenuated Examples Examples are – BCG vaccine used for tuberculosis – Measles/mumps/rubella/varicella vaccine (MMRV) is used routinely in childhood and has been very successful in largely eradicating these diseases in the immunized – Sabin polio vaccine - this agent was used to eradicate polio in the Western hemisphere. It was cheap and gave IgA immunity in the gut. Rarely, however, it reverted to the virulent form and, so as wild type polio disappeared, the vaccine became more dangerous than the risk of acquiring the disease, and so it was replaced by the killed (Salk) polio vaccine. Some places use a combination series of the two types.  Replicating Virus Vectors Viruses that don’t cause human disease are engineered to express (or cause the expression ) of target virus protein. – This allows an immune response to the target virus without infection by it. – Genes for the relevant protein are inserted into the virus vector. – Mimics a real infection to give a strong immune response – Includes Ebola vaccine  Non Replicating Viral Vectors A carrier virus (for example, an Adenovirus) is treated so it can not replicate or cause disease. A gene from the target virus added to the carrier virus so that it expresses the target virus protein. Gives a better immune response than a protein subunit vaccine More easily transported and stored than vaccines needing replicating virus. Viral Vector Vaccines  Types of Inactivated Vaccines These include whole cell, subunit and virus like particles vaccines. They are often given with a substance that increases their immunogenicity (an “adjuvant”, e.g. alum, to increase antibody levels). Conjugation of polysaccharide to protein improves response Boosters to maintain effectiveness  Inactivated Vaccines: nuts and bolts They usually are: – Given by injection, and therefore they do not give a local IgA response (mucosal immunity). – Require multiple doses at specific intervals. – Give immunity that wanes over time, so that reimmunization may be required. – They give an antibody response but not cell mediated immunity. Examples are: – influenza vaccine, hepatitis A vaccine.  Subunit Vaccines Pertussis B. pertussis These are made with purified antigens derived from the pathogen and which are found to produce an effective immune response. These vaccines are less prone to side effects than whole cell and are often very effective, but are expensive.  Subunit Vaccines: Examples Hepatitis B vaccine where the outer coating (surface antigen) is used Haemophilus influenzae type B, pneumococcal, and meningococcal vaccines are prepared from bacterial polysaccharde capsular material. As this material is not very immunogenic, it is now often bound to a protein (“conjugated”) to increase its immunogenicity Pertussis (whooping cough) vaccine  Virus like particles Prepared from viral proteins that self assembly to form particles As there is no nucleic acid the particles look like viruses but are incapable of causing disease Examples are the HPV vaccine and Hepatitis B vaccine.  RNA vaccines RNA vaccines are made of mRNA that instructs our cells to produce a viral protein from the target virus. The protein causes an immune response RNA is unstable so needs to be in a lipid envelope and kept at very low temperatures Hard to transport and store. mRNA Vaccines: Mechanism of Action  DNA vaccines Similar to RNA vaccines but more stable Plasmid is injected which includes a gene for a target virus protein Cells make the protein and elicit an immune response More easily stored and transported Has to get into cell nucleus to work Potential for incorporation into genome, (with possible oncogenicity?)  Diphtheria Toxoids These are inactivated toxins. Immunization protects from the action of the toxin. Multiple doses are given, with an adjuvant to increase immunogenicity. These have been very effective vaccines. Examples are tetanus and diphtheria toxoid vaccines.  Mid-way point Questions? To continue next class….  Childhood Immunizations Federal recommendations from National Advisory Committee on Immunizations (NACI). – MOHs and other experts make up NACI Government departments responsible for health (Dept of Health and Wellness in NS) implement these recommendations in the provinces. Affected by resources, policies, priorities, incidence – Provinces differ in the programs – May be given at hospitals, public health clinics, physicians offices, or other sites Have greatly reduced childhood morbidity and mortality.  Effects of Age Maternal antibody may affect response in babies Immature immune system decreases response – Polysaccharide vaccines not effective in 65 yrs. – Chronic conditions such as: Diabetes mellitus, cancer, immunosuppression, renal disease, anemia, hemoglobinopathy, HIV. – Children and adolescents requiring long- term aspirin. Many provinces try to vaccinate everyone  Hepatitis B Individuals infected at an earlier age have greater risk of liver failure, cirrhosis, and carcinoma. Increasing cases in Canada throughout the 80’s. Purified HBsAg (recombinant). 3 doses at 0,1 and 6 months IM. Schedule varies from province to province. Booster not recommended. Seroconversion rates: 90-95% in immunocompetent individuals.  Pneumococcal Vaccines Two vaccines: – Polysaccharide vaccine (23-valent) which will induce immunity against 90% of pneumonia strains of S. pneumoniae. Efficacy ~ 80% in healthy adults. Recommended to repeat vaccinations every 5 years. – Recommended usage: Age over 65 yrs. No spleen, splenic dysfunction or sickle cell disease. Cerebrospinal fluid leaks. All “high-risk” persons who require influenza vaccine.  Pneumococcal Conjugate Vaccine 13 valent conjugated vaccine – Conjugated to diphtheria toxoid Can be given 2,4,6,12-15 months Provides better immunity in small children Improves memory via cell mediated immunity May decrease carriage of covered pneumococci May result in fewer infections in the elderly – An unexpected benefit – Children are a source of organisms for infection of their grandparents  Varicella Vaccine Live attenuated virus vaccine. Given at age 12 months. If given >12 yrs of age, requires 2 doses. Extremely safe with < 5% of children developing several varicella lesions. Over 95% effective in preventing severe varicella infections. Has the potential to make varicella an uncommon disease in North America. Recombinant VZV vaccine used in 60 + people to reduce shingles Chicken pox  Human Papillomavirus Vaccine Subunit vaccine containing protein of up to 9 types of HPV (6,11 16,18 etc). Given to children aged 9-13 (14-26 may benefit) Given in 3 doses;0,2,6 months (or 2 doses 0,6 months) Safe, pain at site, swelling, redness, itching Effective against HPV infection of the groups included Hope to decrease incidence of cervical cancer, also some genital warts  Covid-19 Vaccines Large number of vaccines developed quickly! Include many strategies: – RNA (Pfizer BioNTech; Moderna) – Non replicating viral vector (Oxford/Astra- Zeneca; Johnson & Johnson) Generally highly effective  Summary Immunity can be conferred either through natural infection, passively via administration of antibody or through active immunization. Our current vaccine schedule has dramatically reduced childhood morbidity and mortality. The immunogenicity of a vaccine depends on multiple factors and can be enhanced by adjuvants and hapten conjugates. As a health care worker you may be explaining and helping people deal with vaccine uncertainty.  Fin. Any questions or comments?  Next lecture! Immunology in diagnostic testing!