1. The Use and Efficacy of Vaccines for Hepatitis NOV 10 2015CHEN (STEVEN) GUAN ZARAH KHAN ZUBEIR KHAN PHM142 Fall 2015 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson

2. What is hepatitis?  Hepatitis is the inflammation of the liver.  Can be caused by virus, autoimmune disease, toxic substances, and overdose of certain medication  There are five main types of hepatitis viruses: A, B,C,D, and E  Hepatitis A & E are transmitted fecal-orally  Typically cause acute and self-limiting infections  B, C, and D are transmitted by blood, semen, and other body fluids  Typically result in chronic hepatitis  Symptoms include: flu-like symptoms (acute), cirrhosis, liver failure, jaundice, and liver cancer

3. Viral Hepatitis Vaccines  Vaccines work by causing the body to produce its own protection in the form of antibodies against the disease  Hepatitis A and B vaccines are available  Hepatitis E vaccine is approved in China  Hepatitis A vaccine contain either inactivated hepatitis A virus or live but attenuated form of the virus  Hepatitis B vaccine contains HBsAg  Surface antigen of HBV

4. Hepatitis A Vaccine  Monovalent vaccines : HAVRIX® 1440 AVAXIM® VAQTA®  Combined Vaccines (Hep A and Hep B) TWINRIX®

5. Hepatitis A Vaccine Uses  Pre-exposure immunization:  For long-term prevention of HAV infection  Used for high risk individuals  Illicit drug users  Travellers to HA endemic countries  Individuals from communities that have high endemic rates of HA  Post –exposure prophylaxis :  household and sexual contacts of people infected with HA  contacts in group child care centres and kindergartens  co-workers and clients of infected food handlers

6. Hepatitis A Vaccine Schedule and Efficacy  Schedule  Primary immunization  Booster dose  6 to 36 months later  Efficacy  Safe, clinically well-tolerated, and highly immunogenic  A seroconversion rate of 100%  Booster dose expected to protect against hepatitis A for > 20 years.

7. Hepatitis B Vaccine  Indicated for active immunisation against infection caused by all known HBV subtypes.  Different vaccine types include a.) Recombinant (Hep B) b.) Combination (Hep A + Hep B) c.) Hepatitis B immune globulin (HBIg)  The vaccine is available as a 0.5 or 1mL suspension containing 10 or 20[micro]g of Hepatitis B surface antigen (HBsAg).  Administered intramuscularly in the deltoid region in adults and in the anterolateral thigh in neonates and infants

8. Hepatitis B Vaccine  Monovalent vaccines:  ENGERIX®-B  RECOMBIVAX HB®  Combined Vaccines (Hep A and Hep B)  TWINRIX® and TWINRIX® Junior  INFANRIX hexa™ (DTaP-HB-IPV-Hib)

9. Hepatitis B Vaccine Uses Routine HB immunization is recommended for all children Pre-exposure HB immunization :  Used for high risk individuals which includes  Infants and young children  Immuno-compromised individulas  Individulas from communities that have high endemic rates of HepB Post –exposure prophylaxis:  infants born to HB-infected mothers  persons potentially exposed to blood or bodily fluids containing HB virus  household and sexual contacts of an acute HB case or chronic carrier

10. Hepatitis B Vaccination Schedule and Seroprotection Rates Healthy individuals : Pre-exposure Prophylaxis  Neonates and infants: 10 mcg of HepB  Three Dose: 0, 1, 6-Month SPR: 96.2 – 100%  In Older Children and Adolescents: 10 mcg of HepB  Three Dose: 0, 1, 6-Month SPR: 94.8 – 100%  In Healthy Adults: 20 mcg of HepB  Three Dose: 0, 1, 6-Month SPR: 85 – 100% High risk individuals: Post-exposure Prophylaxis  Neonates of Hepatitis B Carrier Mothers: 10 -20mcg of HepB  Three Dose: 0, 1, 6-Month SPR: 94-100%  Healthcare workers: 20mcg of HepB  Three Dose: 0, 1, 6-Month SPR: 86-100%  Patients Undergoing Haemodialysis : 40mcg of HepB  Four Dose: 0, 1,2, 6-Month SPR: 77.5-80%

11. Hepatitis C Vaccine Development  There are currently no approved vaccine for Hepatitis C virus  Hepatitis virus exist as 7 distinct genotypes with at least 50 subtypes  Highly mutation rate  Limited animal models  Only chimpanzees  Difficult to enroll at risk individuals for trial  Lack of clear marker for protection

12. Hepatitis C Vaccine Development  Chiron Corp gpE1/gpE2 heterodimer vaccine  Developed after discovery of E2 surface protein  High CD4+ response  Stopped at phase II planning stage  Okairos N23-5B Vaccine  Adenoviral vector vaccine  Broad CD4+ and CD8+ T cells secreting multiple cytokines, targeting multiple epitopes  Presence of polyfunctional and proliferative long-term memory population after 1 year  Ongoing phase 2 with results expected in early 2016

13. Summary  Hepatitis is the inflammation of the liver, mostly caused by viral infection  The main types of Hepatitis are A, B, C, D, and E  A and E cause acute infection  B, C, and D cause chronic infections  Hepatitis A and B vaccines are available.  Hep A vaccine is given to people one year of age or older  Havrix consists of the inactivated Hepatitis A virus  Seroconversion rate of 100% after primary vaccination  Booster dose of Havrix given 6-12 months after the first is expected to protect against Hepatitis A for >20 years

14. Summary  Engerix-B[R] (Hep-B [Eng]) is a non-infectious recombinant DNA vaccine containing hepatitis B surface antigen (HBsAg)  IM Hep-B [Engernix] (0, 1, 6 month schedule] has excellent immunogenicity in healthy neonates, infants, children, adolescents, and adults  Seroprotection rate of 85-100% seen 1 month after final dose of vaccine  Hep-B (Eng) was well tolerated and had excellent protective efficacy against HBsAg carriage in infants, children, and neonates born to hepatitis B carrier mothers, as well as other high-risk groups  Hepatitis C currently has no vaccine  Hepatitis vaccine design is very difficult due to virus’s high degree of genetic variation and difficulty with experiment design  Chiron Corp gpE1/E2 vaccine based on surface glycoprotein trial stopped at Phase 2  Okairos N23-5B vaccine using adenovirus to deliver a non-structure protein to stimulate immune memory has shown good promise

15. References 1. Adkins, Julie C., and Antona J. Wagstaff. "Recombinant Hepatitis B Vaccine*." BioDrugs, 1998, 137-58. 2. André, Francis, Pierre Van Damme, Assad Safary, and Jangu Banatvala. "Inactivated Hepatitis A Vaccine: Immunogenicity, Efficacy, Safety and Review of Official Recommendations for Use." Expert Review of Vaccines, 2002, 9-23. 3. Halliday, John, Paul Klenerman, and Eleanor Barnes. "Vaccination for Hepatitis C Virus: Closing in on an Evasive Target." Expert Review of Vaccines, 2011, 659-72. 4. "Hepatitis." WHO. Accessed November 10, 2015. 5. "Hepatitis A Questions and Answers for Health Professionals." Centers for Disease Control and Prevention. May 31, 2015. Accessed November 10, 2015. 6. "Hepatitis B Vaccine." Canadian Immunization Guide. Accessed November 10, 2015. 7. "Hepatitis: MedlinePlus Medical Encyclopedia." U.S National Library of Medicine. Accessed November 10, 2015.

16. References 8. Kong, L., I.a. Wilson, and M. Law. "Structure of Hepatitis C Virus Envelope Glycoprotein E2 Core Bound to Broadly Neutralizing Antibody AR3C." 2013. 9. Law, Lok Man John, Abdolamir Landi, Wendy C Magee, D Lorne Tyrrell, and Michael Houghton. "Progress towards a Hepatitis C Virus Vaccine." Emerg Microbes Infect Emerging Microbes & Infections, 2013. 10. Strickland, G Thomas, Samer S El-Kamary, Paul Klenerman, and Alfredo Nicosia. "Hepatitis C Vaccine: Supply and Demand." The Lancet Infectious Diseases, 2008, 379-86. 11. Whiteman, Honor. "Hepatitis C Vaccine Shows Promise in Early Clinical Trial." Medical News Today. November 16, 2014. Accessed November 10, 2015. 12. Zingaretti, C., R. De Francesco, and S. Abrignani. "Why Is It so Difficult to Develop a Hepatitis C Virus Preventive Vaccine?" Clinical Microbiology and Infection, 2013, 103-09.