Phar413: Immunization
Active Immunization: -stimulates the adaptive immune system -induces immunological memory to a specific antigen -achieved through administration of vaccines -vaccines protect the individual, and also the entire community by providing the "community or herd immunity'
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Inactivated Toxin/Toxoid Vaccines Vibrio cholera---recombinant modified toxin---combined with whole killed organism Clostridium perfringens---inactivated toxin (formalin)---for newborn lambs
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Live Attenuated Vaccines Viruses: 1. polio--types 2 and 3 may revert; also killed vaccine 2. measles--80% effective 3. mumps 4. rubella--now given to both sexes 5. yellow fever--stable since 1937 6. varicella-zoster--mainly in leukemia 7. hepatitis A--also killed vaccine Bacteria: 1. tuberculosis--stable since 1921; also some protection against leprosy
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Specific Ab Preparations: Infectious Agents: 1. Hepatitis B Immune Globulin (HBIG) 2. Rabies Immune Globulin 3. Tetanus Immune Globulin Non-infectious Agents: 1. Rho (D) Immune Globulin 2. Pit Viper Anti-venom 3. Black Widow Spider Anti-venom
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Subunit Vaccines: Virus: 1. Hepatitis B virus -surface antigen can be purified from blood of carriers or produced by yeast by recombinant DNA technology Bacteria: 1. Neisseria meningitidis -capsular polysaccharides or conjugates of groups A, C, gamma, and W-135 are effective; B is non-immunogenic 2. Streptococcus pneumonia -84 serotypes; capsular polysaccharide vaccines contain 23 serotypes; conjugates with five or seven bacterial serotypes now available 3. Haemophilus influenzae B -good conjugate vaccines now in use
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Tumor Vaccines: 1. Killed Tumor Vaccine -killed tumor cell/tumor lysates + adjuvants -melanoma, colon cancer 2. Purified tumor antigens -melanoma antigens; heat shock proteins -melanoma, renal cancer, sarcoma 3. DC (dendritic cell)-based vaccines -DCs pulsed with tumor antigens; DCs transfected with tumor Ags -prostate carcinomas (approved); melanoma; Non-Hodgkin's lymphoma 4. DNA vaccine -immunization with plasmids encoding tumor Ags -Melanoma 5. Cytokine and co-stimulator enhanced vaccines -immunization with plasmids encoding tumor Ags -Melanoma
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Vaccine Efficacy and Safety in Immunocompromised Persons (See slide 31)
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Influenza Vaccine: There are 2 types of influenza Vaccines: 1. Inactivated, killed virus vaccine (shot) is given to patients _______ months and older 2. Live, attenuated virus vaccine is administered ________ and is given to patients __-___ years old (not immunocompromised/pregnant) and generates a _______ immune response
1. 6 months and older 2. intranasal; 2-49 years old; generates MUCOSAL IMMUNE RESPONSE
Immune Response to Vaccines: Cooperation between B and T cells: 1. ______ bind to vaccine Ag 2. B cells become activated 3. Clonal expansion of B cells 4. Plasma cells secrete vaccine-specific antibodies 5. Generation of memory B cells 6. Antigen is process and presented by B cells to _____ cells 7. ____cells (same as previous) recognize antigen via ____ 8. Th cells secrete _____
1. BCRs 6. T helper cells 7. T helper cells; TCRs 8. cytokines -cytokines influence Ab class switch over -better memory B cell response
Subcellular Fragments and Surface Antigen Vaccines Subunit/recombinant Vaccines: 1. Bacterial Capsular Polysaccharide Vaccine: Pneumococcus (Prevnar), H. flu vaccine---both are CONJUGATED TO PROTEIN CARRIER ______ 2. Viral Surface Ag vaccine: __________ 3. recombinant vaccine: against HPV: ______ prevents HPV infection and HPV-mediated cervical cancer in women), also recommended for boys
1. CRM 197 2. Hepatitis B (Engerix-B) 3. Gardasil
Rabies: 1. Active Immunization: _______(live, attenuated or inactivated?) rabies virus vaccine 2. Passive Immunization: Rabies _______ (RIG) -rationale for treatment depends on the perceived risk of rabies exposure
1. Inactivated rabies virus vaccine (Active Immunization) 2. Rabies immunoglobulin (RIG)--(Passive Immunization)
What are the 4 types of vaccines that provide active immunization?
1. Live, attenuated vaccines 2. Whole killed organism vaccines 3. Inactivated toxin/toxoid vaccines 4. Subcellular fragment/subunit surface antigen vaccines
Immune Response to Childhood Immunizations: Vaccine induced immune response in infants/children DIFFERS from the adults: 1. Cellular immune response to vaccine in children is usually skewed towards a __________ 2. Infant immune response is modulated by the specific vaccine 3. Disease protection also depends on SPECIFIC immune response. _______ vaccines ALONE are the LEAST PROTECTIVE because the antigens are ________ and there is no ________ secretion >Example: Protection against ____ depends on both ____ and ____-type cellular immunity
1. Th2-type cytokine 3. Polysaccharide; T-cell INdependent antigens; no cytokine secretion >Example: protection against PERTUSSIS depends on both Ab and Th1-type cellular immunity
Vaccine Additives: Adjuvants Adjuvant Types: 1. Inorganic salts 2. Vaccine delivery systems -Liposomes, ISCOMs, Block polymers, slow release formulations 3. Bacterial products -Bordetella pertusus(with diphtheria, tetanus) -MF59: squalene, oil-in-water emulsion -BCG in bladder cancer 4. Cytokines -IL-2, IL-12, IFN-gamma Name 3 inorganic salt adjuvants routinely used in human vaccinations
1. aluminum hydroxide (alhydrogel) 2. aluminum phosphate 3. calcium phosphate Too toxic for human use: Beryllium hydroxide
Vaccine Additives: Adjuvants Mechanisms of adjuvant activity: 1. Concentrating the Ag at the site of injection, the ____ effect 2. _____ the antigen to the APCs for uptake and processing 3. Direct effects on APCs and lymphocytes via ______- 4. Targets innate immune receptor ___________
1. depot effect 2. delivering the antigen to APCs 3. inflammation 4. TLR (toll-like receptor) inducing cytokine secretion
Routine Adult Immunizations: Tetanus: 1. disease caused by ____ produced by Clostridium tetani 2. Vaccine contains ___________ 3. The tetanus toxoid vaccine is used as a combination vaccine either with ______ and ______ OR with _____ alone
1. toxin 2. formalin inactivated tetanus toxin 3. diphtheria and pertussis (DTP or DTaP) or with diphtheria alone (DT)
Influenza Vaccine takes up to _______ weeks for protection which lasts around ____
2 weeks for protection; last around 1 year
Inactivated Toxin/Toxoid Vaccines: Organism:Clostridium tetani and Corynebacterium diphtheria Vaccine: inactivated toxin (formalin) The Td (tetanus and diphtheria toxoids absorbed, adult) vaccine is given in ______(how many?) doses, with a booster given every _____ years
3 doses; booster every 10 years
Travel Vaccines: 1. Cholera Vaccine -contains INACTIVATED strains of Vibrio cholera -indicated only for individuals travelling to or residing in countries where cholera is endemic or epidemic 2. Plague Vaccine -contains killed Yersinia pestis, the disease is highly contagious 3. Typhoid vaccine -the typhoid vaccine may be either ____, _____ strain of Salmonella typhi OR _____ form, which contains either ___ S. typhi or the ________
3. Typhoid vaccine -the typhoid vaccine may be either ORAL, LIVE ATTENUATED strain of Salmonella typhi OR PARENTERAL form, which contains either INACTIVATED S. typhi or the CAPSULAR POLYSACCHARIDE
Immune Response to Childhood Immunizations: Survival of ___________ determines long-lasting immunity in children and also in adults. ________ for these memory plasma cells are LIMITED in number
Ab-secreting plasma cells; survival niches
Which of the following are examples of Killed Vaccines? Choose all that apply: A. Salk Polio Vaccine B. Typhoid C. Cholera D. Influenza E. Rabies F. Pertussis
All of them: A. Salk Polio Vaccine (Inactivated Polio Virus (IPV)) B. Typhoid: inactivated Salmonella typhi C. Cholera: inactivated strains of Vibrio cholera D. Influenza: Quadrivalent, inactivated strains of two influenza B and two influenza A strains (H1N1 & H3N2) for 2013-14 E. Rabies: inactivated rabies virus vaccine F. Pertussis inactivated Bordetella pertussis bacteria
Examples of Live, Attenuated Vaccines: Bacterial vaccine ______ for tuberculosis -contains live M. bovis Bacille Calmette-Gue'rin
BCG (Bacille Calmette-Gue'rin) for tuberculosis
Passive Immunization is the ONLY type of immunization useful for patients A. whose immune system is compromised B. with certain types of acute infection, & toxins are in circulation C. Both A and B
C. Both A and B
Killed Vaccines: Diptheria-tetanus toxoids and acellular pertussis ________ adsorbed Vaccine (DAPTACEL) is used mostly for childhood immunization
DTaP
Passive Immunization is the ONLY type of immunization useful for patients 1. whose immune system is compromised 2. with certain types of acute infection, & toxins are in circulation. A __________-specific antibody is required to NEUTRALIZE INFECTION/TOXIN. Examples include the ______, _______, and ______antibodies
High titer specific Ab; rabies Ab, Botulinum Ab, and Hepatitis B Ab
Non-specific Immune Globin Intravenous (IVIG) preparations are intended to be administered either ____ or _____
IV or IM
Non-specific Immune Globin Intravenous (IVIG) is a preparation consisting almost solely of Ig___ antibody from ______ sources
IgG; human sources
_________ vaccines are the MOST SUCCESSFUL of all BACTERIAL vaccines
Inactivated Toxins or Toxoids
_______ vaccines contain intact, but non-living organisms and there is NO REPLICATION OF ORGANISM in host
Killed vaccines
Examples of Live, Attenuated Vaccines: What are 3 VIRAL vaccines that are live,attenuated vaccines?
Live attenuated VIRAL vaccines: 1. Sabin polio vaccine (OPV) -contains live attenuated Polio virus -undergone 57 mutations, stable, developed by Sabin 2. Measles, Mumps, and Rubella (MMR) vaccine -measles and mumps vaccine is developed in chick embryo -rubella vaccine is prepared in human diploid cell culture 3. Influenza Vaccine (FluMist) -for 2014-2015, all live attenuated influenza vaccine (LAIV), the nasal spray vaccine, is QUADRIVALENT -contains 2 influenza B, and 2 influenza A strains (H1N1 and H3N2)
_________ vaccines contain MUTATED LIVE PATHOGEN that no longer causes disease
Live, attenuated
Comparison between Living vs. Non-living Vaccines: Living: -preparation: attenuation (not always feasible) -administration: may be natural route (e.g. oral); may be single dose -adjuvant(a substance that enhances the body's immune response to an antigen): NOT REQUIRED -safety: may revert to virulence -heat lability (for tropical use): requires COLD chain -cost: low -duration of immunity: usually years -immune response: IgG, IgA CELL-MEDIATED
Non-Living: -preparation: inactivation -administration: injection; usually multiple doses -adjuvant: USUALLY REQUIRED -safety: pain from injection -heat lability (for tropical use): satisfactory -cost: HIGH -duration of immunity: may be long or short -immune response: MAINLY IgG; little or no cell-mediated
Therapeutic Cancer Vaccines: -Tumor antigen-specific antibody or T cell response against by actively immunizing patients _________ (Sipuleucel-T), first FDA approved cancer vaccine: autologous ____-mediated ____ cancer immunotherapy
PROVENGE (Sipuleucel-T); Dendritic Cell-mediated (DC-mediated); PROSTATE cancer immunotherapy
Killed Vaccines: The PERTUSSIS killed vaccine is administered in combination with ______ and _______ vaccine as ______
Pertussis, Diptheria, Tetanus toxoid; DTP killed vaccine
Effectiveness of Vaccines for Some Common Infectious Diseases (see slide 7) The disease _________ has been eradicated from the planet thanks to vaccination (0 cases in 2009)
Polio (paralytic)
Examples of Inactivated Toxin/Toxoid Vaccines include ________ and _________
Tetanus and Diphtheria
Hypersensitivity to Vaccine Components: Preservatives: The preservative _____ is found in very low concentration only in the ____(live or killed?) FLU VACCINE
Thimerosol; KILLED flu vaccine
T or F: Flu vaccines are reformulated annually due to predicted new viral strains
True
T or F: Influenza Vaccine is strongly recommended for at-risk individuals such as INFANTS, the ELDERLY, PREGNANT WOMEN (no the live,attenuated vaccine), and individuals with certain health conditions
True
T or F: Passive Immunization provides IMMEDIATE protection
True
T or F: Recent Study shows that the live, attenuated influenza INTRANASAL vaccination is better than the 'shot'
True
T or F: The mutated live pathogen's (contained in live, attenuated vaccines) ability to replicate also increases the risk of actually developing the disease
True
T or F: There are usually no contraindications for Non-specific Immune Globin Intravenous (IVIG) preparations
True
The two forms of immunization are ______ and _______
active and passive
Purpose of Immunization: To prevent infection or treat diseases through activation of ______immunity or through administration of _______
adaptive immunity; pre-formed antibody Edward Jenner, 1796 -first scientific demonstration of the principle of immunization -pre-exposure to cowpox virus conferred protection against more virulent smallpox virus Pasteur, 100 years later demonstrated that, -altered preparations of microbe can generate immunity against fully virulent pathogens: cholera, rabies, anthrax
ACTIVE immunization stimulates the ________ immune system to produce _______, and generates ______-mediated immunity
adaptive; antibodies; cell-mediated
Vaccine Additives: An ________ is a substance that aids another substance in its action
adjuvant
Hypersensitivity to Vaccine Components: -vaccine safety is an overriding consideration One of the common concerns with vaccines is the potential for ________
allergenicity
Influenza Vaccine is commonly administered _____ prior to flu season, which usually occurs from the months ____ to ______, and can be administered concurrently with other live or inactive vaccines
annually; Nov-May,
Vaccine Induced Antibody Response: Neutralization of Microbes and Toxins: A. _______ prevent the binding of microbes to cells, blocking infection B. _______ inhibit the spread of microbial infection to healthy cells C. ______ neutralize toxins and block the binding of toxins to cellular receptors
antibodies
Non-specific Immune Globin Intravenous (IVIG) preparations are used in ____________ disorders
antibody immunodeficiency disorders
Principle of Vaccination: Vaccines mimic the course of natural infection without infecting the person Induces an _____ response via ____-mediated immunity -generates pool of memory T and B cells specific to the vaccine antigen -Memory T and B cells respond quickly and vigorously to future infection -Vaccinated person is protected
antibody resonse; cell-mediated immunity
Subcellular Fragments and Surface Antigen Vaccines ____(are or are not?) virulent, are met with mixed success, and require a _________
are NOT virulent; requires booster
Inactivated Toxin/Toxoid Vaccines usually require _______ immunization
booster
Killed vaccines often require _________ to maintain optimum immunity
booster doses
Travel Vaccines: The most commonly required travel vaccines are for prophylaxis against _____, ______, and ______
cholera, plague, and typhoid
Routine Adult Immunizations: Tetanus The tetanus toxoid vaccine is used as a combination vaccine either with diphtheria and pertussis (DTP or DTaP) or with diphtheria alone (DT) The _________ formulation is most commonly used in WOUND MANAGEMENT
divalent (DT)
Vaccine Additives: Adjuvants Adjuvants are added to a vaccine formulation to elicit an ____, more ____, and _________ lasting immune repsonse
earlier, more potent, and longer lasting immune response
Hypersensitivity to Vaccine Components: Some vaccine organisms are grown in in chick embryo and the ______ in final vaccine product may cause an allergic reaction in patients with _____ allergy
egg protein; egg allergy Note: New flu vaccine is prepared in cell culture system
Subcellular Fragments and Surface Antigen Vaccines contain a ______ of a _______(antigen)
fragment of a microorganism
Patients with HIGH-DOSE __________ (>2mg/kg/day, >2 weeks) should NOT be given LIVE ATTENUATED VACCINES
high-dose corticosteroids Note: However, a risk of disease often outweighs the risk of vaccination--a physician should decide
Live, attenuated vaccines typically confer ______(short or life-long?) protection with one dose
life-long protection with one dose
Hypersensitivity to Vaccine Components: The antibiotic ______ is contained in some viral vaccines
neomycin
Rabies: 2. Passive Immunization: Rabies Immunoglobulin (RIG) -rationale for treatment depends on the perceived risk of rabies exposure WHO recommended post-exposure prophylaxis regiment includes ONE dose of _____ and a series of viral vaccine shots on days ____, ____, ____, and _____
one dose of RIG; series of viral vaccine shots on days 3, 7, 14, and 28
_______ immunization involved administration of PRE-FORMED ANTIBODIES
passive immunization Note: antibodies obtained from human or animal donors, developed immunity either from previous infection or from immunization
Immune Response to Childhood Immunizations: Short-lived antibody response to vaccine in children is partially due to NON-SURVIVAL of formed __________
plasma-blasts
The most successful Subcellular Fragments and Surface Antigen Vaccines are composed of ____________ (these are the antigens that the immune cells recognize first)
polysaccharides
Non-specific Immune Globin Intravenous (IVIG) preparations are ________, reflecting the Ab diversity in donor population, and provide immunologic protection form a WIDE VARIETY OF INFECTION
polyvalent -GammaGard -Polygam -Flebogamma
PASSIVE immunization DOES NOT use the body's own immune system. It relies on the administration of _________
pre-formed antibodies
Live, attenuated vaccines are usually contraindicated in __________ and in _______ patients
pregnancy; immuno-compromised patients
Killed Vaccines are usually ______(safe or harmful?) in immuno-compromised persons
safe
Subcellular Fragments and Surface Antigen Vaccines are usually ______(safe or unsafe?) for use in immuno-compromised patients
safe
Influenza Vaccine: The 2014-2015 influenza vaccine provides protection against both _____ and _____ influenza >13 approved influenza vaccine formulations available in: 1. Trivalent formulations contain 3 strains A/California/7/2009 (H1N1)-like; A/Texas/50/2012 (H3N2)-like; B/Massachusetts/2/2012-like 2. Quadrivalent formulations contain 2 strains of influenza A (H1N1 & H3N2) and 2 strains of Influenza B virus that includes B/Brisbane/60//2008-liike
seasonal and H1N1 influenza
Non-specific Immune Globin Intravenous (IVIG) preparations provides only ________(long-term or short-term?) _______(active or passive?) immunity
short term (~1 month); Passive immunity
Inactivated Toxin/Toxoid Vaccines tend to induce _______(long-term or short-term?) immunity, due to lack of adequate _______ generation
short-term; memory cell
Live, attenuated vaccines tend to produce a _____(strong or weak?) immune response bc the organism can replicate in the host
strong
Inactivated Toxin/Toxoid Vaccines ______ and ______ toxoids are based on formalin INACTIVATED EXOTOXINS
tetanus and diphtheria toxoids >tetanus and diphtheria toxoids adsorbed, adult (Td)
Routine Adult Immunizations: Tetanus The tetanus toxoid vaccine is used as a combination vaccine either with diphtheria and pertussis (DTP or DTaP) or with diphtheria alone (DT) The ________ vaccine is used in routine pediatric immunizations
trivalent (DTP or DTaP)
Rabies virus can remain latent in patients' body up to _____ post-exposure
up to 1 year post-exposure
Active immunization is achieved through the administration of _______
vaccines Note: the word 'vaccine' comes from the latin worod 'vaccinus' which means from cows
Killed vaccines stimulate a _______(stronger or weaker?) immune response compared to live-attenuated vaccines
weaker
