Vaccinology 101 for Fellows
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1 Vaccinology 101 for Fellows Meg Fisher, MD Medical Director, The Children s Hospital Monmouth Medical Center An affiliate of the Saint Barnabas Health Care System Long Branch, NJ
2 Disclosures I have no disclosures. I may be mentioning off label uses of vaccines.
3 Objectives/Outcomes Understand the immunologic basis for immunization and mechanisms to elicit Review route of vaccine administration Discuss the role of adjuvants Define correlates and surrogates
4 Basis for immunization Passive immunization: preformed antibody provided, temporary protection Active immunization: antigen(s) presented to evoke immunologic response, temporary or long lasting depending on the agent
5 Immunizing Antigens Live attenuated viruses or bacteria: serial passage, reassortants Killed microbes Inactivated components: purified proteins or polysaccharides, chemical modifications (conjugates), recombinant technology
6 Antibody Response T cell independent: B cells acting alone, polysaccharides, do not induce memory T cell dependent: T and B cells together, induces memory for boosted responses Antibodies: neutralize, opsonize, activate complement, promote phagocytosis
7 Routes and Sites Mucosal: oral or intranasal Intramuscular: a must for some adjuvants, avoid injecting into fat, use thigh or deltoid Subcutaneous: thigh or deltoid preferred Intradermal: volar forearm preferred
8 Preservatives, Additives, Adjuvants and Residuals Thimerosal, phenol, 2-phenoxyethanol Sugars, amino acids, proteins (gelatin, albumen, cow derived stuff) Aluminum salts enhance immune response Antibiotics, formaldehyde, cellular products (egg, yeast)
9 Adjuvants Enhance immune response, or not Aluminum salts were the first used Novel adjuvants being studied New adjuvants: ASO4 = adjuvant system 04 contains a derivative of monophosphoryl lipid A (MPL) absorbed onto aluminum salt
10 Correlates of Protection Absolute, relative, cocorrelate, surrogate Serologic: antibody - most often used Cell mediated immunity: rarely measured Surrogates: usually antibody, predictors Efficacy studies are the gold standard
11 Vaccine Preventable Diseases Hepatitis B, rotavirus, diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, Streptococcus pneumoniae, influenza, measles, mumps, rubella, varicella, hepatitis A, Neisseria meningitidis, human papillomavirus
12
13 Hepatitis B vaccines Purified hepatitis B surface antigen Recombinant uses: Saccharomyces cerevisiae Intramuscular, avoid fat Formaldehyde treated, adjuvant (aluminum) Correlate: ELISA anti-hbs 10mIU/ml
14
15 Rotavirus Reassortant Vaccines RotaShield: tetravalent rhesus reassortant (G types 1, 2, 3, 4) withdrawn RotaTeq: pentavalent bovine reassortant (G types 1, 2, 3, 4 and P1A) Oral route, no adjuvants No clear correlate, surrogate: serum IgA
16 Attenuated Rotavirus Vaccine Rotarix: Serial passage of human strain (RIX4414); propagated on Vero cells Oral No adjuvant No clear correlate, surrogate: serum IgA
17
18 Diphtheria Vaccine Toxoid: formaldehyde treatment of Corynebacterium diphtheriae toxin Combined with tetanus toxoid +/- pertussis Intramuscular Aluminum salt adjuvant Correlate: toxin neutralization IU/mL
19
20 Tetanus Vaccine Formaldehyde treatment of Clostridium tetani toxin Combined with tetanus toxoid +/- pertussis Intramuscular Aluminum salt adjuvant Correlate: toxin neutralization 0/1 OI/mL
21
22 Pertussis Vaccines Whole cell: suspension of inactivated bacteria Acellular: purified components: pertussis toxoid + filamentous hemagglutinin +/- pertactin, +/- fimbriae types 2 and 3 Combined with tetanus, diphtheria toxoids Intramuscular Correlate of protection unknown
23
24 Oral Polio Vaccine Live attenuated; types 1, 2 and 3 propagated in monkey kidney cells (VERO) Oral No adjuvants Correlate: serum neutralization 1:4 to 1:8 dilution
25 Inactivated Polio Vaccine Formaldehyde inactivated viruses propagated in monkey kidney or human diploid cells Intramuscular No adjuvants Correlate: serum neutralization 1:4 to 1:8 dilution
26
27 Hib Polysaccharide Vaccine Purified polysaccharide capsule: polyribosylribotol phosphate (PRP) Intramuscular No adjuvant Correlate: ELISA 1 mcg/ml
28 Hib Conjugate Vaccines PRP covalently linked to a carrier protein: tetanus toxoid, diphtheria toxoid, CRM 197 (mutant diphtheria toxin), OMP (outer membrane protein complex of N. meningitidis) Intramuscular Adjuvant in OMP product Correlate: ELISA 0.15 mcg/ml
29
30 Pneumococcal Polysaccharide 23 purified capsular polysaccharides: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, 33F Intramuscular or subcutaneous No adjuvant Correlate: ELISA mcg/ml
31 Pneumococcal Conjugate Saccharides of capsular antigens of 4, 6B, 9V, 14, 18C, 19F, and 23F conjugated to diphtheria CRM 197 protein Intramuscular Aluminum phosphate adjuvant Correlate: ELISA mcg/ml
32
33 Inactivated influenza Vaccines Viruses propagated in embryonated chicken eggs; inactivated and then split processes vary by vaccine (see package inserts) Intramuscular No adjuvants Correlate: hemagglutination inhibition 1:40
34 Live Cold Adapted Vaccine Reassorted strains: cold adapted, temperature sensitive, attenuated Master donor virus (6): H and N from wild Nasal spray No adjuvant Correlate: hemagglutination inhibition 1:40
35
36 Measles Vaccine Attenuated measles virus derived from Enders' attenuated Edmonston strain; propagated in chick embryo cell culture Subcutaneous No adjuvant Correlate: microneutralization 120 miu/ml
37
38 Mumps Vaccine Jeryl Lynn (B level) strain of mumps Virus; propagated in chick embryo cell culture Subcutaneous No adjuvant Correlate: not determined; neutralizing antibodies are detected
39
40 Rubella Vaccines RA 27/3 attenuated strain; propagated in WI-38 human diploid lung fibroblasts Subcutaneous No adjuvant Correlate: immunoprecipitation miu/ml
41
42 Varicella Vaccine Oka/Merck attenuated strain; propagated in a variety of cell lines (human embryonic lung, embryonic guinea pig, human diploid cells) Subcutaneous No adjuvant Correlate: neutralization 1:64
43
44 Hepatitis A Vaccines Inactivated vaccines; propagated in human diploid cells Intramuscular Aluminum salt adjuvant (hydroxide or hydroxyphosphate sulfate) Correlate: ELISA 10 miu/ml
45
46 Meningococcal Polysaccharide Polysaccharide antigens from N meningitidis, Group A, C, Y and W-135 Subcutaneous No adjuvant Surrogate: serum bacteriocidal antibodies
47 Meningococcal Conjugate Polysaccharide antigens from N meningitidis, Group A, C, Y and W-135 individually conjugated to diphtheria toxoid protein Intramuscular No adjuvant Surrogate: serum bacteriocidal antibodies
48
49 HPV Vaccine: Gardasil Recombinant uses S. cerevisiae: capsid (L1) proteins-types 6,11,16,18 produced and selfassembled into virus-like particles (VLP) Intramuscular Aluminum hydroxyphosphate sulfate adjuvant Correlate: not established
50 HPV Vaccine: Cervarix Recombinant uses Baculovirus in Trichoplusia ni insect cells: capsid (L1) protein produced and self assemble (VLP) Intramuscular ASO4 adjuvant: MLP on aluminum hydroxide Correlate: not established
51 Smiling is a contagious condition!
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