Vaccines_2023_Ingrid Herrmann.pptx
Transcript
Vaccines Lecture by Dr. Herrmann Objectives 1. Define active, passive, natural, and artificial immunity 2. Define herd immunity; understand how vaccines protect populations as well as individuals 3. List different types of vaccines, as well as their advantages and disadvantages 4. List advantages...
Vaccines Lecture by Dr. Herrmann Objectives 1. Define active, passive, natural, and artificial immunity 2. Define herd immunity; understand how vaccines protect populations as well as individuals 3. List different types of vaccines, as well as their advantages and disadvantages 4. List advantages and disadvantages of attenuated and inactivated vaccines 5. Describe why polysaccharide vaccines are commonly conjugated to inactivated proteins 6. Describe side effects and risks of vaccines for example reasons vaccines are contraindicated in some patients Immunization • Immunization is the process of inducing immunity. • Acquired immunity is immunity you develop over your lifetime. • Can be done in multiple ways Active immunity Passive immunitya Natural immunity Artificial immunity Terminology Active Immunity Results when exposure to a disease organism or vaccine triggers the immune system to produce antibodies to that disease. The person’s own immune system produces the response! Can last years or even for the lifetime of the individual. Passive Immunity Provided when a person is given antibodies to a disease rather than producing them through his or her own immune system. Only last for a few weeks or months. Active Immunity Antibodies Results from Takes effect Length of efficacy Produced by memory cells? Passive Immunity Produced inside of Introduced from the body outside of the body •Direct infection •Breast milk •Vaccination •Injection •Mother to baby through the placenta Over time Immediately (typically several weeks) Long-term to lifelong Yes Short-term No Terminology Natural Immunity Acquire by natural means, like an infection or from your mother (for example mother’s milk) Can be either active or passive immunity Artificial immunity Sources of immunity are given to you for a specific purpose They include vaccinations or immunoglobulin treatments Can be either active or passive immunity This is an example of artificial, passive immunity! If antibodies are given to a patient (passive immunization) or they generate their own, their antibodies will bind and neutralize extracellular pathogens Vaccines • Vaccine: preparation of pathogen or its products used to induce active immunity • Protect in 2 ways: Protect individual (direct) Prevent spread in population (indirect) • Herd immunity • Herd Immunity: A situation in which a sufficient proportion of a population is immune to an infectious disease (through vaccination and/or prior illness) to make its spread from person to person unlikely. Vaccines 5 general types of vaccines: I. Attenuated II. Inactivated III. Subunit, recombinant, polysaccharide, and conjugate vaccines IV. Toxoid vaccines V. RNA vaccines & viral vectors What happens after a vaccination? • Memory lymphocytes activate faster and produce stronger responses than naïve lymphocytes. • Memory T and B cells require less antigen and costimulation to activate. • Memory responses can peak in a few days, naïve responses may take weeks to peak. Attenuated vaccines • Contains weakened form of pathogen Can replicate inside the host Disease is mild or undetectable • How do we attenuate a pathogen? Using tissue cultures (cells), embryonated eggs, or animals. Monoclonal antibodies can be used to select for attenuated pathogen strains Attenuated vaccines Advantages Single dose usually induces long-lasting immunity due to microbe multiplying in body Can also inadvertently immunize others by spreading If it’s an attenuated intracellular pathogen (virus), it will generate a robust CTL (CD8 T cells) response Disadvantages Can sometimes cause disease in immunosuppressed individuals Can occasionally revert or mutate, become pathogenic (rare) Generally not recommended for pregnant women Usually require refrigeration to keep active Attenuated Vaccines: Examples Live vaccines are used to protect against: Measles, mumps, rubella (MMR combined vaccine) Rotavirus Smallpox Chickenpox Yellow fever Inactivated vaccines • Pathogen CANNOT replicate • Advantages Cannot cause infections or revert to pathogenic forms • Disadvantages No replication, so no amplification in vivo; immune response is limited Several booster doses usually needed Often contain adjuvants to enhance immune response Adjuvants • An adjuvant is a substance that enhances the immune response to antigens. • They do this by providing “danger signals” to APCs (dendritic cells), which present antigens to T cells Adjuvant typically work by binding receptors in host cells, causing the production of pro-inflammatory cytokines and activation of APCs Costimulation receptors are upregulated • Aluminum hydroxide and aluminum phosphate are the most used adjuvants. Inactivated vaccines Inactivated whole agent vaccines: contain killed microorganisms or inactivated viruses Treated with formalin or other chemical that does not significantly change surface epitopes Examples: • • • • Hepatitis A Flu (shot only) Polio (shot only) Rabies Toxoid Vaccine Toxoids: toxins treated to destroy toxic part, retain antigenic epitopes Inactivated toxin is given in the vaccine Host antibody response neutralizes the toxin, preventing disease Examples: Diphtheria vaccine (TDaP) Tetanus vaccine (TDaP) Vaccines utilizing pathogen components Broad category includes subunit, recombinant, polysaccharide, and conjugate vaccines use specific pieces of the germ — like its protein, sugar, or capsid (a casing around the germ) give a very strong immune response that’s targeted to key parts of the germ They can also be used on almost everyone who needs them Booster shots frequently needed Vaccines utilizing pathogen components Examples Hib (Haemophilus influenzae type b) disease Hepatitis B HPV (Human papillomavirus) Whooping cough (part of the DTaP combined vaccine) Pneumococcal disease Meningococcal disease Shingles Conjugated Vaccines Note: Some subunit vaccines (pneumococcal and Hib vaccine) must be conjugated to an inactivated protein to evoke a response in people with weak immune systems Elderly and children Both Hib and the pneumococcal vaccine (PCV13) use polysaccharides from the bacteria’s capsules Remember that polysaccharide cannot be presented by MHC! The conjugated protein is needed to activate T cells. S. pneumoniae: Capsule Distinctive Properties / Virulence Factors Capsule: major virulence factor, anti-phagocytic • • • • • • polysaccharide, more than 83 different serotypes some serotypes more virulent (e.g. serotype 3) non-encapsulated “rough” strains occur in URT 7 serotypes cause 85% of the human invasive disease (23 serotypes cause 90% of disease) antibody to the capsule is protective – vaccine target Major causes of community-acquired pneumonia by site *202 0 S. pneumoniae, H. influenzae, N. meningitidis • All these organism were common causes of invasive disease in children prior to their vaccine becoming available. • The vaccine for each is against their main virulence factor: their capsule! • The capsule of each is polysaccharide based. • Recall, that only peptides can be presented by MHC I+II. • For patients with underdeveloped/weak immune systems (children/elderly), the bacterial polysaccharides are conjugated to a protein to stimulate T cell responses. • Vaccination prevents invasive disease, not colonization! S. pneumoniae: Vaccines PPSV (Pneumovax 23) Purified capsule polysaccharide from 23 most common isolates Works well in adults, but no response in child < 2 yr old Covers 90% of isolates – still used in adults because of broad coverage Every five years for persons at risk PCV13 (Prevnar 13) conjugate vaccine Addition of six new purified capsule polysaccharides to cover capsule serotypes not in the older PCV-7 (including 19A) Conjugated to inactivated diphtheria toxin, works in children! Attenuated vs Inactivated vaccines Messenger RNA vaccines (mRNA vaccines) • Researchers have been studying and working with mRNA vaccines for decades • mRNA vaccines make proteins in order to trigger an immune response (for example spike protein) • mRNA vaccines have several benefits compared to other types of vaccines, including shorter manufacturing times and, because they do not contain a live virus, no risk of causing disease in the person getting vaccinated. • mRNA vaccines are used to protect against: COVID-19 Clinical Correlate • https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-todate.html Viral vector vaccines (J & J vaccine) • Viral vector vaccines use a modified version of a virus that is different from the virus being targeted • The modified version of the virus is called a vector virus. • The COVID-19 vector virus is not the virus that causes COVID19, but a different, harmless virus • Besides being used in vaccines, viral vectors have also been studied for gene therapy, to treat cancer, and for molecular biology research • has expired and is no longer available for use in the United States as of May 6, 2023 Newest COVID vaccine: Novavax • Novavax protein subunit COVID-19 vaccine • Protein subunit vaccines contain pieces (proteins) of the virus that causes COVID-19 • The virus pieces are the spike protein. • The Novavax COVID-19 vaccine contains another ingredient called an adjuvant (It helps the immune system respond to that spike protein) • After learning how to respond to the spike protein, the immune system will be able to respond quickly to the actual virus spike protein and protect you against COVID-19. Common Vaccine Side Effects • Local side effects Swelling, redness • Systemic side effects Fever, pain, allergic reaction • MMR and thrombocytopenia 1 out of ~40,000 doses Compared to the actual disease, the side effects of vaccines are usually rare and much easier to deal with than the actual disease themselves! When are vaccines contraindicated? • Severe allergic reaction To previous dose or vaccine component • Immunodeficiency • Pregnancy Such as MMR, influenza, chicken pox • Certain chronic medical conditions Asthma, diabetes, heart/kidney disease (decision between patient and physician) Check vaccine info prior to administration! Goals of immunization programs • Selective immunization strategy Protect those at highest risk • Mass immunization strategy I. Eradication Smallpox II. Elimination Polio, measles III. Control S. pneumoniae, H. influenzae, N. meningitidis The campaign to eliminate poliomyelitis • Polio 3 types of virus; enter through mouth (fecal/oral) Virus infects throat and GI tract, moves to blood From bloodstream can invade nerve cells • Salk vaccine (mid-1950s) All 3 virus types; INACTIVATED Dramatically lowered incidence but requires multiple doses • Sabin vaccine (early 1960s) All 3 virus types; ATTENUATED Better mucosal immunity Since 1988, the number of cases of polio have dropped 99%! Selective vaccination • Vaccine given specifically to those at increased risk of disease • Occupational/behavioral risk Hepatitis B • Travelers Yellow fever • Outbreak control Meningitis, measles Reliable Web Sites Clinical Correlate-The future of vaccines • Did you know that scientists are still working to create new types of vaccines? Here are 2 exciting examples: • DNA vaccines are easy and inexpensive to make—and they produce strong, long-term immunity. • Recombinant vector vaccines (platform-based vaccines) act like a natural infection, so they're especially good at teaching the immune system how to fight germs.
