MIC 205 Immunization and Vaccination Ch 17 PDF

MIC 205 - Microbiology Lecture 15: “It will only hurt for a second! I PROMISE!” Ch. 17: Immunization and Vaccination Lecturer: Patrick Daydif Office: UCENT 356 Phone: (602) 496-0599 Email: [email protected] Office Hours: Please refer to Canvas (or by appointment) The best way to contac...

MIC 205 - Microbiology Lecture 15: “It will only hurt for a second! I PROMISE!” Ch. 17: Immunization and Vaccination Lecturer: Patrick Daydif Office: UCENT 356 Phone: (602) 496-0599 Email: [email protected] Office Hours: Please refer to Canvas (or by appointment) The best way to contact me and answer your questions is Face to Face. Types of Acquired Immunity Natural – Active – Passive Artificial – Active – Passive 2 Naturally Acquired Active Immunity This immunity develops after antigens (e.g., microbial pathogens) enter the body by natural processes such as infection and, in response, the body’s immune system forms antibodies and memory cells. Length of Immunity Varies – In some cases, the immunity may be life-long, smallpox, measles, chickenpox, yellow fever – In other cases, the immunity may be lost after only a few years diphtheria, tetanus – In other cases, even for a lesser period influenza, pneumonia 3 1  Naturally Acquired Passive Immunity When antibodies produced in the body of an individual (Mother) are naturally transferred into the body of other individuals (child) The child develops immunity by receiving the antibodies. Certain antibodies (IgA) are also transferred from mother to infant in breast milk during nursing. – These antibodies, called maternal antibodies, are short lived. – Most antibodies will remain with the child for about three to six months. – There has been examples of the presence of antibodies circulating a year after the transfer, but the immunity is greatly reduced at this point. 4 Artificially Acquired Active Immunity When a carefully chosen antigen (e.g., vaccine, chemically altered or inactivated toxins called toxid) is intentionally introduced into a body to be immunized. This immunity is artificial because the antigens are intentionally or purposely introduced, and it is active because the recipient’s immune system synthesizes antibodies. Vaccines are now available against many infectious agents. – Cholera, tuberculosis, plague, pneumonia, rocky mountain spotted fever, smallpox, polio, tetanus, influenza, measles, rabies – Toxoid are currently available for protection against diphtheria and tetanus 5 Artificially Acquired Passive Immunity This is known as antibody therapy, by the introduction of antibody-rich serum (blood plasma devoid of clotting factors) taken from diseased individual who has recovered and given to a susceptible individual currently with disease. – Referred to as monoclonal or convalescent therapy. COVID 19: Bamlanivimab, Casirivimab, and Sotrovimab These neutralizing antibodies allow for an immediate response from the individual with the disease, but the presence of the antibodies is only 2 to 3 weeks. Examples of protections from – Viral diseases such as Hepatitis B, Chickenpox, COVID-19, – Bacterial disease such as Botulism, diphtheria, tetanus, staphylococcal- poisoning, where toxins are involved in disease causation. – Anti-serum or anti-venom is delivered as a form of 6 artificially acquired passive immunity 2 Passive vs. Active Immunization Threshold concentration to prevent signs and symptoms 7 Vaccines Historical (Smallpox) General types of vaccines – Attenuated (live, weakened) – Killed (inactivated) – Subunit / Toxoid – Vector Based Recombinant Herd immunity Method of Administration Safety Concerns 8 History of the SmallPox Vaccine 1500 AD to today: Outbreaks have been documented throughout the world. – In 1694, marks the death of Queen Mary II/ Ben Franklin lost a son (1736). – In 1751, London recorded 3,538 deaths, which was a record at the time. – In 1776, 50% of the Continental army fell ill with small poxes during Quebec's invasion. – Last natural out-break was in Somalia in 1977. – The WHO declared smallpox eradicated in 1980. 17th Century saw the first treatment regimens. – Use of Variolation Army, Royalty, & Slaves (Individuals with economic value) Edward Jenner (1798) documents his uses of variolation and challenges with smallpox. U.S. vaccine agency established in 1813 – Congress required the U.S. Post Office to carry the smallpox vaccine for free. By 1874, many governments require their citizens to get vaccinated. 1882: Anti-Vaccination arguments spread. 1905: Supreme court case Jacobson v. Massachusetts 1922: Supreme court case Jacobson in Zucht v.King 3  Smallpox Immunization; 19th century Cowpox pustules used to vaccinate humans. Concept: attenuated live viruses In 1898 calf lymph became the standard method of vaccination for smallpox in the U.K. Considerations of a Vaccine Example: Influenza Virus – Remember! Virus Subtypes Determine by the “H” & “N” antigen on the surface of the virus. – 15 variations of H and 9 variations of N The regions in blue are the parts of the antigen that variety from strain to strain. – Each flu season, these epitopes will be different, and therefore the antibodies from the previous year’s vaccine will not bind. The regions in red are the parts of the antigen or antigen that are conserved from strain to strain. – Each flu season, these epitopes are similar to the previous year virus, and the antibodies from the previous year’s vaccine should bind. – BUT this region does not prevent the 11 binding of the virus to the host cell. Attenuated (live, weakened) Microbe that has been cultivated under conditions that disable their virulent properties. 3 methods to design this type of vaccine. – (1) Remove virulence genes from the microbe. – (2) Use closely-related but less dangerous organisms to produce a broad immune response. (Cowpox will offer immunity for smallpox) 12 4  Attenuated (live, weakened) (3) Microbe has been cultivated under different conditions. – Culturing the microbe in alternative cell lines with closely related receptors. – Microbe will “learn to grow better” nonhuman cell lines. – When exposed to humans' cell, the microbe will slowly replicate, & the Immune system will be able to build a strong response 13 Influenza “FLU” Vaccine 14 Killed/Inactivated Vaccines Contain killed, but previously virulent, microorganisms that has been inactivated with chemicals or heat. – Must not change the shape of the antigens (epitopes) of the microbe. Remember heat can cause proteins to misfold and change shape. – The humoral response will create a response to multiple epitopes of the microbe. Stimulates a TH response that promotes antibody-mediated immunity Safer – Organism cannot replicate or mutate Less Effective The immune system will only create one humoral response, unless boosters are given. Must give Multiple doses (“boosters”), to get achieve “active immunity.” 15 5 Subunit Vaccines Antigenic fragments (protein) of microbe can create an immune response. – A small piece of the microbe! Must be able to elicit an immune response to protect the individual from signs and symptoms. – Protein subunit Hepatitis B: is composed of the viral envelope protein Human papillomavirus (HPV): is composed of the capsid protein – Modified toxins Tetanus, Diphtheria, Rattlesnake toxoid (dogs). Stimulate antibody-mediated immunity Safer: no risk of replication Less effective requires multiple doses (“boosters”) 16 Vector Based Recombinant Vaccines The genes for antigens of pathogens inserted into non- pathogen Those non-pathogens are injected into an individual and will express the genes from the pathogen to elicit an immune response. Johnson and Johnson uses adenovirus vector vaccine 17 Vector Based Recombinant Vaccines Vaccinia virus (cowpox) infection protects the person against lethal smallpox infection. Current research is attempting to clone multiple genes from different pathogens into Vaccinia virus to offer immunity to – Smallpox – Bacillus anthracis (Anthrax) – Human papillomavirus (HPV) – Human immunodeficiency virus (HIV) – Herpes simplex Vaccinia virus has uniquely large DNA genome for a virus. – Required to express its genes. Is required for encoding various enzymes and proteins Involved in viral DNA replication and gene transcription Express attachment proteins. – Researchers need to clone these genes from other organisms to become antigens for immunity. This involves molecular techniques such a PCR, DNA isolation, and using restriction enzymes. 6 COVID 19 Vaccines (BioNTech/ Pfizer and Moderna) 19 COVID 19 Vaccines 20 COVID 19 Vaccines 21 7 COVID 19 US Approved Vaccines Vaccine Pfizer-BioNTech Moderna J&J/ Janssen adenovirus vector Type mRNA vaccine mRNA vaccine vaccine BNT162b2, JNJ-78436735, Other names mRNA-1273 (Comirnaty) Ad26.COV2.S Doses 2 (21 days apart) 2 (28 days apart) 1 Booster Yes (1-2) Yes (1-2) Yes (1) Effectiveness Up to 95% Up to 94.1% 52%–81.9% 14 days after 2nd 14 days after 2nd 14 days after 1st Full vaccination dose dose dose Authorized 12/11/2020 & Dec. 18, 2020 & Feb. 27, 2021 & ? (EUA)& (Full) 8/2021 2/2022 Eligibility Ages 5 and up Ages 18 and up Ages 18 and up Cost $ 20 $ 33 $6 No safety concerns were found in animal studies: Studies in animals receiving a Moderna, Pfizer-BioNTech, or Johnson & 22 Johnson (J&J)/Janssen COVID-19 vaccine before or during pregnancy found no safety concerns in pregnant animals or their babies. Cancer Vaccines There are two types of cancer vaccines – Vaccines that protect an individual from a viral infection that can result in cancer such as HPV or Hepatitis B (See subunit vaccines) – Vaccines that treat existing cancer, called treatment vaccines or therapeutic vaccines. These work to boost the body's immune system, elicit a cell mediated response known cancer antigens. MUC-1: Breast HER-2 /neu: Breast, Ovarian, bladder, Pancreatic, Stomach IGF1R: Prostate, Breast, Colon PDL-1: Lung Sp17: Ovarian, Sperm 23 Method of Administration Direct injection – Direct to the bloodstream or intermuscular but will not induce secretory antibodies in the mucus membranes. – Stimulate Immune response in the lymph nodes Inhalation or Nasal Spray – Fast method, Easy, but tends not to make it to the bloodstream, very little response in the lymph nodes. – May induce secretory antibodies (IgA) in the mucus membranes Oral – Must not be deactivated by the low pH of stomach acids & and be able to diffuse from the intestines/stomach – May induce secretory antibodies (IgA) in the mucus membranes Subcutaneous – Induced just under the skin (Epidermis) – Allows for the microorganism to replicate locally and NOT throughout the body 24 – Can induce a systemic immune response 8  Importance of Administration Method Direct injection of a vaccine will place the antigens in the tissues and elicit an immune response in the lymphatic system. The drawback to this method is it will allow the microbe into the body, and the immune system will start its protection in the lymphatic system. Inhalation and Oral vaccine will place antigens in the mucus membrane. This could elicit a localize response by M-cell and the Peyer’s patch. This would active B-cells to produce IgA antibodies in the mucus membrane, therefore, prevention of the microbe crossing the mucus membrane. The drawback to this method mucociliary clearance of the vaccine, thus, low level response. Vaccine Safety & Problems General side effects – Interferon Response Residual virulence – Attenuated vaccine Vaccine Recalls – Gardasil ( HPV) and COVID-19 J&J vaccine Contamination – 2004 flu vaccine contamination, Thimerosal as a bacteriostatic agent Public misconceptions – Jenny McCarthy announced that her son was diagnosed with autism due to the preservation agent in MMR vaccination. – Andrew Wakefield This has been rejected by scientific studies, with McCarthy's claims that vaccines cause autism are not supported by any medical evidence (National Institute of Mental Health) The original paper (Mid 90’s) by Andrew Wakefield formed the basis for her claims but was based on manipulated data and fraudulent research. Even with his articles retracted, Wakefield had planned a venture to profit, plus McCarty taking to media platforms has now led to the MMR vaccine scare. 26 Vaccine Safety & Problems Stability – Does the Vaccine need refrigeration? 1955 Salk Polio vaccine (Inactivated) 1962 Sabin polio vaccine (Attenuated) – COVID 19 Pfizer: Requires: -80˚ for storage and last at 4˚C for 30 days Moderna: Requires: -20˚ for storage and last at 4˚C for 30 days J&J Requires: 4˚C storage Allergic reaction – Gelatin/MMR, Eggs/ Influenza Research Cost/Government – FDA, CDC, WHO – 1 attempt cost about 1.1 billion per drug;1/250 will make it market. 27 9  Does Everyone need to be Vaccinated? Herd immunity – Describes a type of immunity that occurs when the vaccination of a portion of the population (or herd) provides protects to unprotected individuals. More difficult to maintain a chain of infection when large numbers of a population are immune. The higher the proportion of individuals who are immune, the lower the likelihood that a susceptible person will contact an infectious individual. 28 Herd Immunity thresholds for Protection Herd immunity Disease Transmission threshold Diphtheria Saliva 85% Measles Airborne 94% Mumps Airborne droplet 86% Pertussis Airborne droplet 94% Polio Fecal-oral route 86% Rubella Airborne droplet 85% Smallpox Social contact 85% COVID-19 Airborne droplet ?70%? Source::History and Epidemiology of Global Smallpox Eradication From the training course titled "Smallpox: Disease, Prevention, and Intervention". The 29 CDC and the World Health Organization. 10