Goal and Objectives Goal: Provide the clinician with an overview of some recent developments in vaccinations relevant to transplantation. Objectives: Cheap Shots: Update on Vaccinations Discuss the mechanism and function of vaccines Review some recently FDA approved vaccines: - Hepatitis B Vaccine recombinant, adjuvanted (Heplisav-B) - Meningococcal Group B Vaccine (Bexsero & Trumenba) David J. Quan, Pharm.D., BCPS Pharmacist Specialist-Solid Organ Transplant - Zoster vaccine recombinant, adjuvanted (Shingrix) UCSF Health Review some useful vaccination resources available Health Sciences Clinical Professor of Pharmacy UCSF School of Pharmacy 2 “ A Brief History of Vaccination Date Event 400 BC Hippocrates describes mumps, diphtheria, and epidemic jaundice “An ounce of prevention is worth a 1100s Variolation with dried scab materials from smallpox patients pound of cure.” 1798 Edward Jenner publishes work vaccination against smallpox 1879 Louis Pasteur creates first live attenuated vaccine (chicken cholera) 1893 Mass production of diphtheria antitoxin 1945 Influenza vaccine licensed in the United States 1977 Last case of naturally occurring smallpox -Benjamin Franklin 1981 Hepatitis B plasma-based vaccine developed 1968 Recombinant hepatitis B vaccine developed 1995 Live varicella vaccine licensed 2014-5 Meningococcal serogroup B vaccines licensed 2017 Recombinant zoster vaccine 3 4
How Vaccines Work Different Types of Vaccines Vaccine Type Vaccines Live, attenuated Measles, mumps, rubella (MMR) Pass virus through cell cultures to Varicella (Varivax) attenuate virus (unable to replicate) Influenza intranasal (FluMist) Inactivated Polio (IPV) “Killed” virus that retains immunogenicity Hepatitis A (Havrix, Vaqta) Toxoid Tetanus, diphtheria (part of Tdap) Inactivated form of toxin Subunit / conjugate Hepatitis B (Engerix-B) Pneumococcal (Pneumovax 23) Part of the pathogen used to provoke Meningococcal (Menactra) immune response Other Ingredients Action Preservatives Antimicrobial, single dose=no preservative Adjuvants Increases immune response 5 Presentation Title 6 How Vaccines Are Made Vaccines Eliminate Disease Elimination of Measles in the United States MMWR 1995;43:1. https://www.cdc.gov/mmwr/preview/mmwrhtml/00039679.htm MMWR 2007; 54:2-92. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5453a1.htm Vaccine Fact Book 2013. Pharmaceutical Manufacturers of America, September 2013. 7 Presentation Title 8 Presentation Title
General Principles Before transplantation - Complete vaccine series (earlier the better) Hepatitis B Vaccines Serologic monitoring to determine immunity - Document vaccinations in patient’s medical record After transplantation - Optimal time to give vaccines post-transplant is not well defined Wait at least 3-6 months after transplant to vaccinate No evidence linking vaccinations to rejection episodes - Live vaccines should NOT be given post-transplant - Assess seroconversion (serologic monitoring) Danziger-Isakov L. Am J Transplantation . 2013;13:311-317. 9 10 Hepatitis B Vaccine Hepatitis B Vaccine New and Updated Recommendations Traditional Vaccination is the mainstay of hepatitis B virus prevention Universal Hepatitis B vaccine within 24h of birth - Yeast-derived recombinant HBsAg Testing HBsAg-positive pregnant women for HBV DNA - Decreased response: Smoking, obesity, diabetes, aging, chronic Post-vaccination testing of infants whose mother’s HBsAg medical conditions, drug use, male, immune suppression status remains unknown 3-dose vaccine series protective (anti-HBs ≥10mIU/mL) Single-dose revaccination for infants born to HBsAg-positive - >90% adults <40 years old women not responding to initial vaccine series - 30-55% and 75% achieve anti-HBS ≥10mIU/mL after 1 & 2 doses Removal of permissive language delaying birth dose until Hepatitis B immune globulin (HBIG) after hospitalization - Plasma-derived (human donors) Vaccination of persons with chronic liver disease - Passively acquired anti-HBs detected for 4-6 months - Post-exposure prophylaxis and liver transplantation Schillie S, Vellozzi C, Reingold A, et al. MMWR Recomm Rep 2018;67(No. RR-1):1–31. 11 12
Hepatitis B Vaccine, Adjuvanted Hepatitis B Vaccines: Old and New Heplisav-B Engerix-B Recombivax- Heplisav-B Twinrix HBsAg from recombinant HB Hansenula polymorpha yeast Doses 3 3 2 3-4 Cytosine phosphoguanine (CpG) 1018 adjuvant Viral antigens HBsAg HBsAg HBsAg HBsAg mimicked HAVAg - 22-base Adjuvant Aluminum Aluminum CpG 1018 Aluminum oligodeoxyribonucleotide: 5’-TGACTGTGAACGTTCGAGGATGA-3’ hydroxide hydroxide Toll-like 9 hydroxide receptor - Toll-like 9 receptor agonist Bacterial/viral pathogen Derivation rDNA yeast rDNA yeast rDNA yeast rDNA yeast recognition source Adjuvant from bacterial DNA - Increases magnitude and quality of antibody response to Manufacturer GSK Merck Dynavax GSK antigen Cost $203 $224 $276 $358-478 Heyward WL. Vaccine . 2013;31:5300-5305. 13 14 Patient Factors That Affect Response Seroprotection Rates Decrease With Age Hepatitis B, Adjuvanted Hepatitis B Vaccine, Adjuvanted Hepatitis B Vaccine, Hepatitis B Vaccine Age Hepatitis B vaccine, Hepatitis B vaccine* Adjuvanted (Engerix-B) (years) Adjuvanted* (Engerix-B) (Heplisav-B) (Heplisav-B) Total trial population (N=6665) 95.4% 81.3% N SPR N SPR 18-29 174 100% 99 93.9% Patients with diabetes (N=961) 90.0% 65.1% 20-39 632 98.9% 326 92.0% Aged 40-70 (N=5434) 94.6% 78.7% Male (N=3353) 94.5% 78.8% 40-49 974 97.2% 518 84.2% Obesity (N=3241) 94.7% 75.4% 50-59 1439 95.2% 758 79.7% Smokers (N=2082) 95.9% 78.6% 60-70 1157 91.6% 588 72.6% * Heplisav-B week 24, Engerix-B week 28. SPR = Seroprotection Rate Jackson S, et al. Vaccine . 2018;36:668-674. Dynavax Technologies Corporation. FDA Advisory Committee Briefing document. Heplisav-B prescribing information]. Berkeley, Ca: Dynavax Technologies Corporation; 2017. 15 16
Hepatitis B Vaccine Side Effects Hepatitis B Vaccines Dosing Reaction Hepatitis B Vaccine, Hepatitis B Vaccine Vaccine Dose Day 0 Month 1 Month 2 Month 6 Adjuvanted (Engerix-B) (Heplisav-B) Engerix-B 1mL (20mcg) IM X X X Dose 1 Dose 2 Dose 1 Dose 2 Dose 3 Engerix-B hemodialysis 2mL (40mcg) IM X X X X Local Recombivax HB 1mL (10mcg) IM X X X Injection site pain 38.5% 34.8% 33.6% 24.7% 20.2% Recombivax HB hemodialysis 1mL (40mcg) IM X X X Injection site redness 4.1% 2.9% 0.5% 1.0% 0.7% Twinrix (hepatitis A & B) 1mL IM X X X Injection site swelling 2.3% 1.5% 0.7% 0.5% 0.5% Heplisav-B 0.5mL (20mcg) IM X X Systemic Fatigue 17.4% 13.8% 16.7% 11.9% 10.0% Headache 16.9% 12.8% 19.2% 12.3% 9.5% Malaise 9.2% 7.6% 8.9% 6.5% 6.4% Fever 1.1% 1.5% 1.8% 1.7% 1.8% 17 18 Hepatitis B Vaccines Key Points Several hepatitis B vaccines are available Hepatitis B vaccine, adjuvanted (Heplisav-B) - Higher seroprotection rates compared to conventional vaccine Diabetes, obese, smokers, and aged 40-70 years Meningococcal Vaccines Seroprotection occurs earlier Efficacy based on surrogate marker (seroprotection) - 2-dose regimen Interchangeability and dosing schedule - 2-dose vaccine applies only to Heplisav-B When able, same manufacturer’s vaccine should be used for series Series consisting of one Heplisav-B dose and vaccine from different manufacturer, should consist of 3 total doses (follow 3-dose schedule)* *Schillie S. Recommendations of the Advisory Committee on Immunization Practices for Use of a Hepatitis B Vaccine with a Novel Adjuvant. MMWR Morb Mortal Wkly Rep 2018;67:455–458. DOI: http://dx.doi.org/10.15585/mmwr.mm6715a5. 19 20
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