Foundations in Pharmacology PHRM2005 Vaccines - Part B PDF

Foundations in Pharmacology PHRM2005 Dr Ricky Lareu Vaccines – Part B 1 2 Information See Lecture Outline document for Key Concepts, Learning Outcome and Lecture Summary Reading and reference material: Mim’s Medical Microbiology 5th Ed, Chapter 34 & 35 3 Adjuvants An adjuvant is a substance that is...

Foundations in Pharmacology PHRM2005 Dr Ricky Lareu Vaccines – Part B 1 2 Information See Lecture Outline document for Key Concepts, Learning Outcome and Lecture Summary Reading and reference material: Mim’s Medical Microbiology 5th Ed, Chapter 34 & 35 3 Adjuvants An adjuvant is a substance that is added to a vaccine to increase the body's immune response to the vaccine. Adjuvants increase the immunity induced by a vaccine in a number of ways:  Inducing activation of Toll-like receptors (TLR) on dendritic cells to improve antigen presentation.  Forming an antigen depot which allows antigen to persist and to leak out slowly over time. Freund’s complete adjuvant – water-in-oil emulsion and dead mycobacteria, effective but suitable for animals only. Aluminium salts are now most commonly used and are powerful adjuvants. 4 Child Immunisation Schedule In order to provide best protection, it’s recommended children receive vaccines as soon as their immune systems are sufficiently developed  With additional booster shots often required to achieve full immunity WA Child immunisation scheme funded by the National Immunisation Program:  https://healthywa.wa.gov.au/Articles/A_E/Childhoodimmunisation-schedule Information for childhood (infant, children and adolescents) and adult immunisation schedules (inc. pregnant, Aboriginal). New vaccines or modifying existing ones are tested to make sure that they do not reduce the effectiveness of other vaccines i.e. new vaccines interfering with other vaccines. Australian Immunisation Handbook https://immunisationhandbook.health.gov.au/ 5 Herd Immunity An important epidemiologic aspects of disease transmission: Herd immunity - If enough individuals in a population are immunized, this will reduce or stop transmission of the infection. When too many parents decide that their child will not be immunized, because think risk to child is low, this may contribute to the disease becoming more common and increasing the chance of their child and other’s becoming ill. Herd immunity also protects those that cannot be immunised due weak immune system:  new borne and pre-term baby, pregnancy  illness, old age and immunocompromised http://www.mlive.com/news/index.ssf/2014/12/how_do_vaccinations_work_the_s.html Brief video explaining herd immunity: http://vk.ovg.ox.ac.uk/herd-immunity 6 Adverse Reactions Local Systemic pain, swelling, redness at site of injection fever, malaise, headache common with inactivated vaccines nonspecific usually mild and self-limited Anaphylaxis faint (vasovagal syncope) may be unrelated to vaccine Anaphylaxis – most severe adverse effect Usually happens within 15 minutes Year rare (1/1 million) but can be life-threatening Administer epinephrine (e.g. EpiPen) and antihistamines 7 Symptoms of Anaphylaxis Fainting Onset Anaphylaxis Usually at the time or soon after injection Usually some delay between 5–30 minutes after injection Symptoms Skin Respiratory Cardiovascular Gastrointestinal Neurological Pale, sweaty, cold and clammy Red, raised, and itchy rash; swollen eyes, face; generalized rash. Normal to deep breaths Noisy breathing from airways obstruction (wheeze or stridor) that indicates obstruction of the trachea or larynx.) Bradycardia (Abnormally slow heartbeat) Tachycardia (A heart rate that exceeds the normal range for a resting heart) Transient hypotension Hypotension Nausea/Vomiting Abdominal cramps Transient loss of consciousness, good response once prone Loss of consciousness, little response once prone 8 Chemotherapy versus Vaccination An important difference is that chemotherapy is given after exposure to infection , whereas vaccination is usually given before exposure  Chemotherapy offers short-term that wanes once drugs is no longer given  Vaccination can give protection for years to life-time without repeated treatment.  Vaccines also protect others around us 9 Passive Immunity Passive immunity involved the administration of antibodies (or immune cells) from a donor that has already responded to an antigen. The recipient’s immune system is not involved:  Natural – mother to baby  Artificial – administration of antibodies Results in the immediate protection against:  sever and acute infection from pathogens and toxins o  Examples: tetanus toxin, Rabies bite, venoms from snakes, spiders and fish In immunocompromised individuals due to illness and infants at risk; that have an immature immune system eg premature babies 10 Heterologous Sera Therapy Heterologous sera therapy – antibodies raised in animal and used in humans, polyclonal antibodies One of the first successful antimicrobial immunotherapy In the pre-antibiotic era, used to treat diphtheria, scarlet fever, pneumococcal pneumonia, and others In WWI used to treat British soldiers’ infections for tetanus, Abs raised in horses. Complication was serum sickness due to foreign proteins:  Antigen-antibody complexes, hypersensitivity type III reaction  Illness worsened with each subsequent treatment e.g. organ and joint damage  Treatment less effective due to faster donor antibody clearance 11 Homologous Sera Therapy Homologous sera therapy – donor antibodies from humans, also polyclonal antibodies Fewer side-effect and lasts longer Because antibodies in sera are dilute, in 1940 developed a way to concentrate and extract the gamma-globulin fraction – contains antibodies Now use pooled sera from 1000’s of individual, purify out IgG fraction  e.g. RhD antigen (Rhogam) – given to mothers that are Rh-ve before delivery to not develop Rh+ antibodies and affect future pregnancies Now called Immunoglobulin Therapy 12 Monoclonal Antibody Therapy Monoclonal antibody therapy – produced by hybridoma technology, modern In vitro generation of specific antibodies – fusion of a plasma cell with an immortal cell (cancer cell) Unlike Immunoglobulin therapy which is extracted from human sera, where there are antibodies against many epitopes,  a monoclonal antibody preparation only has one epitope i.e. specific for one type of antigen Many monoclonal antibody types are now licensed for clinical use, with most against cancers, one against respiratory syncytial virus 13 Summary Adjuvants help improve immune reactions to vaccine antigens. The Child Immunisation Schedule is government-funded and has been formulated to protect children, and into adulthood, against major diseases. For effective control of disease within a community, a significant number of the population need to be immunised, called herd immunity. Herd immunity protects those that cannot be immunised and are vulnerable. Side-effects to vaccination are usually mild but can be severe e.g. anaphylaxis. Passive immunity is the administration of exogenous antibodies to give immediate protection: heterologous, from animals; homologous, from other humans Monoclonal antibody therapy involves the production of single-epitope antibodies raised in vitro. 14