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Hib, Pneumo, Hep A and B

Hib, Pneumo, Hep A and B. MedCh 401 Lecture 4. Haemophilus influenzae b. Gram negative coccobacillus Respiratory pathogen, primarily of children Encapsulated and unencapsulated strains Unencapsulated strains from respiratory tracts of adults. Hib Transmission. Person-to-person

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Hib, Pneumo, Hep A and B

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  1. Hib, Pneumo, Hep A and B MedCh 401 Lecture 4 KL Vadheim Lecture 4

  2. Haemophilus influenzae b • Gram negativecoccobacillus • Respiratory pathogen, primarily of children • Encapsulated and unencapsulated strains • Unencapsulated strains from respiratory tracts of adults KL Vadheim Lecture 4

  3. Hib Transmission • Person-to-person • Respiratory droplets, contact with respiratory secretions • Humans are only host • May be carried in respiratory tract for long periods and transmitted to many people before causing disease KL Vadheim Lecture 4

  4. H. influenzae capsule • Composed of polyribosylribitol phosphate (PRP), a repeating polymer of ribosyl and ribitol phosphate • Polysaccharide • Six serotypes, a - f KL Vadheim Lecture 4

  5. Type b capsule • Antibody to serotype b conferred type-specific protection • Type b strains account for 95% of all strains causing invasive disease ( bacteremia and meningitis) KL Vadheim Lecture 4

  6. Hib vaccine efficacy • Incidence of invasive Hib disease in children <5 years of age has dropped from >20/ 100,000 in 1990 to near zero in 2004 KL Vadheim Lecture 4

  7. Composition of Hib vaccines KL Vadheim Lecture 4

  8. ActHIB • Lyphilized vaccine • Reconstituted with: • Saline • DTP (sanofi Pasteur) • DTaP (Tripedia; sanofi Pasteur) KL Vadheim Lecture 4

  9. Hib Conjugates • C. diphtheriae CRM197 - nontoxic variant of diphtheria toxin • Tetanus toxin - toxoided with formalin • Outer Membrane Protein Comples from B11 strain of N. meningiditis serogroup B KL Vadheim Lecture 4

  10. Manufacturing processes • H. influenzae grown in fermenters • PRP purified from cells • Conjugates grown in fermenters, proteins purified, tetanus toxin toxoided • Conjugation reactions: • ActHIB PRP covalently bound to tetanus toxoid • HibTITET PRP coupled to CRM197 by reductive amination • PedVaxHIB PRP covalently bound to N. meningitidis outer membrane protein complex (OMPC) KL Vadheim Lecture 4

  11. Pneumococcal Disease • Leading cause of morbidity and mortality for all ages, worldwide • U.S. annual incidence: • 15-30 cases/100k • case fatality rate 15-20% • Major cause of : • invasive infections: bacteremia, meningitis • pneumonia, upper respiratory disease, acute otitis media, sinusitis KL Vadheim Lecture 4

  12. Streptococcus pneumoniae • Gram + coccus • Increasingly resistant to antimicrobial agents • Commonly occurs as carrier state • Both capsulated and non-capsulated • ~90 serotypes KL Vadheim Lecture 4

  13. Pneumococcal Vaccines KL Vadheim Lecture 4

  14. Comparative efficacy • Prevnar - 100% • Pneumovax - ~57% KL Vadheim Lecture 4

  15. Capsular serotypes • Differ in prevalence KL Vadheim Lecture 4

  16. Pneumococcal Vaccines • Serotypes 4, 6B, 9V, 14, 18C, 19F and 23F (Prevnar) have been responsible for ~80% of invasive pneumococcal disease in children <6 • Pneumovax-23 - additional 16 serotypes gains protection against ~10% KL Vadheim Lecture 4

  17. Manufacturing Pneumococcal vaccine • Pneumovax 23 - capsular polysaccharides purified from 23 types of S. pneumoniae • Prevnar - capsular polysaccharides from 6 S. pneumoniae serotypes are purified, then conjugated to diphtheria CRM197 protein KL Vadheim Lecture 4

  18. Hepatitis A • Systemic viral infection with liver pathology • Symptoms indistinguishable from most other viral hepatitis infections • Incubation period is ~15 - 50 days • Disease may range from asymptomatic, to hepatitis, to fatal infection KL Vadheim Lecture 4

  19. HepA Transmission • Fecal-oral transmission • Person-to-person • Infected food or water • Replicates in the liver • Humans are the only natural host • No chronic infection or carrier state • Virus shed in feces ~3 weeks, starting 1-2 weeks before symptoms KL Vadheim Lecture 4

  20. HepA vaccine efficacy • >95% seropositive after one dose • 100% seropositive after two doses KL Vadheim Lecture 4

  21. Hepatitis A Manufacturing • Attentuated virus is propagated in MRC-5 cells • Cells are harvested by centrifugation • Cells are lysed to form a viral suspension • Virus is inactivated with formalin • Adsorbed onto aluminum adjuvant KL Vadheim Lecture 4

  22. Hepatitis A Vaccines KL Vadheim Lecture 4

  23. Hepatitis B • Systemic infection with liver pathology • Symptoms indistinguishable from Hepatitis A or other viral hepatitis infections • Can cause primary hepatocellular carcinoma • Lifetime risk of infection: • 100% for high-risk groups (e.g., IV drug users) • <20% for general U.S. population KL Vadheim Lecture 4

  24. Hepatitis B Carriers • 200-300 million worldwide • 1-1.25 million in U.S. • 90% of neonates and 6-10% of infected adults will become carriers • Carriers can infect others KL Vadheim Lecture 4

  25. Hepatitis B Transmission • No host outside humans (no other reservoir of infection) • Bloodborne transmission • parenteral • mucosal • perinatal • Communicable 1-2 months before and after onset of symptoms KL Vadheim Lecture 4

  26. Hepatitis B Vaccine • Recombinant • Old vaccine was pooled human plasma KL Vadheim Lecture 4

  27. Hep B Vaccine Manufacturing • Cloned, purified Hepatitis B Surface Antigen (HBsAg) • Genetically engineered into Saccharomycescerevisiae (yeast) cells • Yeast grown in fermenters • HBsAg release by yeast cell disruption • Purified • Formalin-treated (Recombivax only) • Adsorbed to aluminum adjuvants KL Vadheim Lecture 4

  28. Hepatitis B Vaccines KL Vadheim Lecture 4

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