Micro chapter 45: Vaccines and Antisera for the Prevention and Treatment of Infectious Diseases Active immunization – administration of all or part of a microorganism, or a modified product of that organism, to cause an immune response mimicking infection, but with little to no risk to the patient Vaccine – immunizing agent derived from microorganisms consisting of: - Live, attenuated microorganisms Killed microorganisms or parts of microorganisms Killed whole agents Extracts of microorganisms Toxoid – inactivated bacterial toxin that is no longer toxic (can’t damage us) but still induces an antibody response Passive immunization – receiving exogenous antibodies to prevent disease - Passive immunization can be given through the placenta, through colostrum (breast milk), or by injection Things you can use for passive immunization is IG through muscles, IG given by IV, human plasma, and animal antibodies Immune globulin (IG) – mixture of antibodies made from blood plasma - Specific IG – antibodies made from plasma from people with high #’s antibodies to a specific microorganism Intravenous IG (IVIG) – used to treat immunodeficiencies, inflammatory conditions, and cancers Attenuate – decrease in the virulence of a microorganism Antigen – molecule recognized by the immune system Herd immunity – immunity provided to the population when large #’s of the population are vaccinated Benefits of a vaccine to society – herd immunity, and decrease in health care costs No vaccine though is completely safe or effective, and they can have side effects Active immunization with vaccines or toxoids leads to prolonged immunity, and is the preferred method, as opposed to passive immunization (administering IG’s) As a rule, antibody responses to killed vaccines or toxoids can take several weeks to develop, and often need 2-3 doses at several week intervals to elicit an adequate and persistent immune response - With live vaccines, most people will develop protective immunity within 2 weeks To maintain protective antibody concentrations over a lifetime, many vaccines must be readministered as booster doses - Ex: booster doses of tetanus and diphtheria toxoids should be given every 5-10 years Since most infectious disease have short incubation periods (usually less than 2 weeks), active immunization is often ineffective after exposure - Sometimes, passive immunization with specific globulins or antitoxins can be used after exposure Antibody-containing stuff can inhibit the immune response elicited by a vaccine, so you wait to give a live vaccine until passive immunity has gone away, usually about 11 months You use both passive and active immunization together for diseases with long incubation periods, or variable incubation periods Usually, immunity generated by a killed vaccine is not as effective or long lasting as immunity stimulated by a live attenuated vaccine - The live vaccine more closely mimics the natural disease Killed vaccines are easier to make though, and pose no risk for vaccine-associated risk The live, attenuated, intranasal, cold-adapted influenza vaccine (or just live, attenuated influenza vaccine for short) has a weakened form of live flu virus, and is given by a nasal spray instead of injection - Cold adapted – means the virus can grow int eh nose and throat, but not in the lower respiratory tract, where the temperature is higher The live, attenuated flu vaccine is more effective for kids, than the inactivated flu vaccine There is always a small risk that an attenuated vaccine strain will revert to a more virulent form in the host - - Vaccine-acquired paralytic-poliomyelitis (VAPP) – happens in 1 outta every 3 million times the polio vaccine is given o Since polio was eradicated in the 70’s in the US, the only cases of paralysis from polio since then have come from VAPP o So they now recommend using only the inactivated polio vaccine in the US o Countries that didn’t eradicate it though still use the live vaccine o Immunization rates need to stay high, to prevent VAPP from spreading The first licensed rotavirus live vaccine caused intussusception of the intestine, so they had to get rid of that and make new ones with less risk What type of response does the vaccine elicit: - Live, attenuated vaccines – induces B cells, CD8+ T cells, and CD4+ T cells Inactivated organisms, protein antigens, and capsular polysaccharide with a protein carrier – induces B cells and CD4+ T cells, but no CD8+ T cells - Capsular polysaccharides alone – induces only B cells T-cell-independent antigens are characterized by low antibody titers and little memory response, especially in children less than 18 months old - - Capsular polysaccharides induce B cell production of antibody, without any T cell help If you covalently couple (conjugate) the polysaccharide to a protein antigen, the conjugated vaccine instead causes a T-cell dependent response, due to the protein antigen o T-cell dependent antigens cause high antibody levels in young infants, and primes for strong booster responses at revaccination, due to good memory The conjugation of pneumococcal capsular polysaccharides to protein antigens also generates both B cell and T cell – dependent responses, and has caused herd immunity of invasive pneumococcal disease Secretory IgA antibodies produced at the mucosal surface, offer protection against some mucosal pathogens, like flu, polio, rotavirus, etc. - Live attenuated vaccines given to mucosal sites, can induce secretory immunity at the site of initial pathogen contact Correlates of protection – what type of immune response is needed to protect from the pathogen - Some vaccines only induce serum antibodies – ex: HAV, polio, rabies, diphtheria, tetanus, pertussis, and extracellular encapsulated bacteria Other vaccines need both antibody levels and function to protect – ex: mumps, rubella, HIV, meningococci, and pneumococci Secretory antibodies protect against pathogens that need to replicate on the mucosal surface o Ex: flu, polio, and rotavirus Some vaccines need the T cell response – ex: measles, varicella How old you are when you’re immunized is important in determining the immune response to the vaccine - - Newborns receive IgG antibody from their moms, giving them transient protection against some disease that their mom was immune to o Breast milk also has secretory IgA antibodies that protect against intestinal and respiratory tract infections, that the mom was immune to o Both are passive immunization o Mom antibodies may prevent responses to live vaccines though o At birth, the humoral system isn’t fully developed and won’t have a good response to polysaccharide antigens, but it will respond well to protein antigens The elderly also have decreased immune responses, due to immune senescence o So they’re more susceptible to infections How to pick an antigen from a disease: - Immune responses are most often against surface things that the pathogen uses when it invades Sometimes all strains of a pathogen have that antigen, and sometimes some strains do and some strains don’t, so you use multiple antigens for those vaccines Antigenic drift (minor antigen changes) happen every year in flu virus (influenza), causing new strains that need new vaccines o Also, major antigen changes happen every decade, called antigenic shift Some populations are at higher risk for diseases we can vaccinate: - - Influenza – people with heart or lung disease, or those older than 65, or younger than 6 months, are at greater risk, and should be vaccinated Sickle cell disease – causes asplenia, which makes them more at risk for infections with encapsulated organisms, especially pneumococci o They should get the pneumococcal conjugate vaccine o People without spleens are also at the same risk, as well as for flu and meningococci Old people – pneumococci and flu vaccines Health care workers – HBV and rubella Immunocompromised – shouldn’t get live attenuated vaccines, cause it may be pathogenic enough to cause disease The DTaP vaccine (diphtheria, tetanus, acellular pertussis) – the oldest and most successful combination vaccine used in children - It consists of a combo of 2 toxoids (diphtheria and tetanus) and inactivated parts of Bordetella pertussis All pertussis vaccines include pertussis toxin DTaP is preferred to be given at 2, 4, and 6 months old, followed by booster doses at 15 and 18 months, and 4 to 6 years old Then a booster of tetanus toxoid and diphtheria are given every 5-10 years Recently, a new vaccine of tetanus toxoid, reduced dose diphtheria toxoid, and pertussic components, was released, called Tdap - Get Tdap at 11 to 12 years old, and a pertussis booster later in adolescence Also, adults who had DTAP, should get Tdap