A Brief History of Vaccination Date Event 400 BC Hippocrates - - PDF document

▶
a brief history of vaccination date event 400 bc
SMART_READER_LITE
LIVE PREVIEW

A Brief History of Vaccination Date Event 400 BC Hippocrates - - PDF document

Nov 13, 2023 258 likes •372 views

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

slide-1
SLIDE 1

Cheap Shots: Update on Vaccinations

David J. Quan, Pharm.D., BCPS Pharmacist Specialist-Solid Organ Transplant UCSF Health Health Sciences Clinical Professor of Pharmacy UCSF School of Pharmacy

2

Goal and Objectives

Goal:

  • Provide the clinician with an overview of some recent

developments in vaccinations relevant to transplantation. Objectives:

  • 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)
  • Zoster vaccine recombinant, adjuvanted (Shingrix)
  • Review some useful vaccination resources available

“

3

“An ounce of prevention is worth a pound of cure.”

  • Benjamin Franklin
4

A Brief History of Vaccination

Date Event 400 BC Hippocrates describes mumps, diphtheria, and epidemic jaundice 1100s Variolation with dried scab materials from smallpox patients 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 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

slide-2
SLIDE 2 Presentation Title 5

How Vaccines Work

6

Different Types of Vaccines

Vaccine Type Vaccines Live, attenuated

Pass virus through cell cultures to attenuate virus (unable to replicate) Measles, mumps, rubella (MMR) Varicella (Varivax) Influenza intranasal (FluMist)

Inactivated

“Killed” virus that retains immunogenicity Polio (IPV) Hepatitis A (Havrix, Vaqta)

Toxoid

Inactivated form of toxin Tetanus, diphtheria (part of Tdap)

Subunit / conjugate

Part of the pathogen used to provoke immune response Hepatitis B (Engerix-B) Pneumococcal (Pneumovax 23) Meningococcal (Menactra)

Other Ingredients Action Preservatives

Antimicrobial, single dose=no preservative

Adjuvants

Increases immune response

Presentation Title 7

How Vaccines Are Made

Vaccine Fact Book 2013. Pharmaceutical Manufacturers of America, September 2013.

Presentation Title 8

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
slide-3
SLIDE 3 9

General Principles

  • Before transplantation
  • Complete vaccine series (earlier the better)
  • 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.

10

Hepatitis B Vaccines

11

Hepatitis B Vaccine

New and Updated Recommendations

  • Universal Hepatitis B vaccine within 24h of birth
  • Testing HBsAg-positive pregnant women for HBV DNA
  • Post-vaccination testing of infants whose mother’s HBsAg

status remains unknown

  • Single-dose revaccination for infants born to HBsAg-positive

women not responding to initial vaccine series

  • Removal of permissive language delaying birth dose until

after hospitalization

  • Vaccination of persons with chronic liver disease

Schillie S, Vellozzi C, Reingold A, et al. MMWR Recomm Rep 2018;67(No. RR-1):1–31.

12

Hepatitis B Vaccine

Traditional

  • Vaccination is the mainstay of hepatitis B virus prevention
  • Yeast-derived recombinant HBsAg
  • Decreased response: Smoking, obesity, diabetes, aging, chronic

medical conditions, drug use, male, immune suppression

  • 3-dose vaccine series protective (anti-HBs ≥10mIU/mL)
  • >90% adults <40 years old
  • 30-55% and 75% achieve anti-HBS ≥10mIU/mL after 1 & 2 doses
  • Hepatitis B immune globulin (HBIG)
  • Plasma-derived (human donors)
  • Passively acquired anti-HBs detected for 4-6 months
  • Post-exposure prophylaxis and liver transplantation
slide-4
SLIDE 4 13

Hepatitis B Vaccine, Adjuvanted

Heplisav-B

  • HBsAg from recombinant

Hansenula polymorpha yeast

  • Cytosine phosphoguanine

(CpG) 1018 adjuvant

  • 22-base
  • ligodeoxyribonucleotide:
5’-TGACTGTGAACGTTCGAGGATGA-3’
  • Toll-like 9 receptor agonist
  • Bacterial/viral pathogen

recognition

  • Increases magnitude and

quality of antibody response to antigen

Heyward WL. Vaccine. 2013;31:5300-5305.

14

Hepatitis B Vaccines: Old and New

Engerix-B Recombivax- HB Heplisav-B Twinrix Doses 3 3 2 3-4 Viral antigens mimicked HBsAg HBsAg HBsAg HBsAg HAVAg Adjuvant Aluminum hydroxide Aluminum hydroxide CpG 1018 Toll-like 9 receptor Aluminum hydroxide Derivation source rDNA yeast rDNA yeast rDNA yeast Adjuvant from bacterial DNA rDNA yeast Manufacturer GSK Merck Dynavax GSK Cost $203 $224 $276 $358-478

15

Patient Factors That Affect Response

Hepatitis B, Adjuvanted Hepatitis B Vaccine, Adjuvanted (Heplisav-B) Hepatitis B Vaccine (Engerix-B) Total trial population (N=6665) 95.4% 81.3% Patients with diabetes (N=961) 90.0% 65.1% Aged 40-70 (N=5434) 94.6% 78.7% Male (N=3353) 94.5% 78.8% Obesity (N=3241) 94.7% 75.4% Smokers (N=2082) 95.9% 78.6%

Dynavax Technologies Corporation. FDA Advisory Committee Briefing document.

16

Seroprotection Rates Decrease With Age

Hepatitis B Vaccine, Adjuvanted Age (years) Hepatitis B vaccine, Adjuvanted* (Heplisav-B) Hepatitis B vaccine* (Engerix-B) N SPR N SPR 18-29 174 100% 99 93.9% 20-39 632 98.9% 326 92.0% 40-49 974 97.2% 518 84.2% 50-59 1439 95.2% 758 79.7% 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. Heplisav-B prescribing information]. Berkeley, Ca: Dynavax Technologies Corporation; 2017.
slide-5
SLIDE 5 17

Hepatitis B Vaccine Side Effects

Reaction Hepatitis B Vaccine, Adjuvanted (Heplisav-B) Hepatitis B Vaccine (Engerix-B)

Dose 1 Dose 2 Dose 1 Dose 2 Dose 3

Local Injection site pain 38.5% 34.8% 33.6% 24.7% 20.2% Injection site redness 4.1% 2.9% 0.5% 1.0% 0.7% Injection site swelling 2.3% 1.5% 0.7% 0.5% 0.5% 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%

18

Hepatitis B Vaccines

Dosing

Vaccine Dose Day 0 Month 1 Month 2 Month 6

Engerix-B 1mL (20mcg) IM

X X X

Engerix-B hemodialysis 2mL (40mcg) IM

X X X X

Recombivax HB 1mL (10mcg) IM

X X X

Recombivax HB hemodialysis 1mL (40mcg) IM

X X X

Twinrix (hepatitis A & B) 1mL IM

X X X

Heplisav-B 0.5mL (20mcg) IM

X X

19

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
  • 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.
20

Meningococcal Vaccines

slide-6
SLIDE 6 21

Meningococcal Vaccines

Serogroups A, C, Y, W-135

  • Neisseria meningitidis (meningococcus) can cause bacterial

meningitis and sepsis, which can be fatal.

  • Five serogroups (groups A, B, C, Y, and W-135) cause a majority
  • f the invasive meningococcal disease.
  • Most common in infants, teens and young adults
  • Patients at risk: Asplenia, complement disorders, HIV-infection
  • Quadrivalent (serogroups A, C, Y, W-135) vaccines available:
  • Menactra (diphtheria toxoid conjugate)
  • Ages 9 months through 55 years
  • Menveo (diphtheria oligosaccharide CRM197 protein conjugate)
  • Ages 2 months through 55 years
  • Menomune (polysaccharide) discontinued in 2017
22

Meningococcal Vaccines

Serogroup B

  • Medical conditions at risk for meningococcal disease
  • HIV infection
  • Functional or anatomic asplenia
  • Persistent complement deficiencies (e.g. C3, C5-9, factor H or D)
  • Patients taking eculizumab (Soliris)
  • Recombinant (serogroup B) vaccines:
  • Bexsero (recombinant Neisserial adhesin A (NadA), Neisserial

Heparin Binding Antigen (NHBA), factor H binding protein (fHbp) and Outer Membrane Vesicles (OMV), aluminum adjuvant)

  • Trumenba (recombinant lapidated factor H binding protein (fHbp)

from subfamilies A05 and B01).

23

Meningococcal Vaccines

Dosing Schedules Vaccine Dose Day 0 Month 1 Month 2 Month 6 Cost Meningococcal A/C/Y/W-135 Menactra 0.5mL IM X $139 Menveo 0.5mL IM X $151 Meningococcal B Bexsero 0.5mL IM X X $396 Trumenba 0.5mL IM X X $319 X X* X $478

*3-dose vaccination regimen recommended when more accelerated immunity is desired (e.g. adolescent during outbreak

24

Meningococcal Serogroup B Vaccines

Immunogenicity

Bexsero Bactericidal Antibody Response Age 18-24 Age 11-17

H44/76 (fHbp) 78% 98% 5/99 (NadA) 94% 99% NZ98/254 (PorA P1.4) 67% 39% Composite endpoint:

1 month post dose 2 11 months post dose 2 88% 66% 63%

Trumenba Bactericidal Antibody Response Age 10-18 Age 18-25

≥-4 fold increase dose 3

PMB90(A22)

86.2% 81.1%

PMB2001 (A56)

92.0% 90.7%

PMB2948 (B24)

81.9% 83.9%

PMB2707 (B44)

88.3% 79.3%

Composite response

85.7% 82.7%

NCT 01423084 LLOQ=1:16 for H44/76; 1:16 for 5/99, 1:8 for NZ98/254. Composite = hSBA ≥LLQ for all three strains. NCT01830855, NCT01352845 LLOQ=1:16 for A22; 1:8 for A56, B24, and B44 Composite = hSBA ≥ LLOQ for all primary strains

slide-7
SLIDE 7 25

Meningococcal Serogroup B Vaccine

Safety Bexsero* Dose 1 Bexsero* Dose 2 Trumenba‡ Dose 1 Trumenba‡ Dose 2 Trumenba‡ Dose 3 Pain (any) 90% 83% 86.7% 77.7% 76% Erythema 50% 45% 16.2% 12.5% 13.9% Fever 1% 5% 6.4% 2% 2.7% Myalgia 49% 48% 24.2% 17.8% 17.6% Arthralgia 13% 16% 21.9% 16.7% 16% Fatigue 37% 35% 54% 38.3% 35.9% Headache 33% 34% 51.8% 37.8% 35.4%

*Ages 10 through 25 years. National Clinical Trial (NCT) Identifier NCT01272180.

‡Ages 18 to 25. National Clinical Trial (NCT) Identifier NCT01352845. 26

Eculizumab Order Panel

Meningococcal Vaccines and Prophylaxis

  • Eculizumab increases risk
  • f meningococcal disease
  • Eculizumab Order Panel
  • Dosing guidance
  • Meningococcal vaccines
  • Meningococcal A/C/Y/W

and

  • Meningococcal B
  • Antimicrobial prophylaxis
  • Ciprofloxacin
  • r
  • Penicillin VK
27

Meningococcal Vaccination

Key Points

  • Two types of meningococcal vaccines: (ACWY) and B
  • Meningococcal conjugate (ACWY)
  • All preteens & teens with booster and children/adults at risk
  • Serogroup B vaccine
  • People >10 years at increased risk for meningococcal disease
  • Two serogroup B vaccines available
  • Same vaccine should be used to complete the series
  • Efficacy in the short-term (antibodies wane with time)
  • Patients on eculizumab at high risk (despite vaccination)
  • Vaccinate at least 2 weeks prior to administration
  • Consider antimicrobial prophylaxis for duration of therapy
https://www.cdc.gov/vaccines/vpd/mening/hcp/adolescent-vaccine.html (accessed 9/3/2018) McNamara LA. High Risk for Invasive Meningococcal MMWR Morb Mortal Wkly Rep 2017;66:734-737. 28

Shingles (Zoster) Vaccines

slide-8
SLIDE 8 29

Varicella Zoster Virus

  • Varicella zoster virus is from the herpesvirus family that

causes chickenpox in children and young adults.

  • Reactivation later in life causes a painful rash (Shingles)
  • Risk of shingles increases with age
  • People at high risk of shingles:
  • Leukemia/lymphoma
  • HIV infection
  • Immunosuppression
  • Several different vaccines available
30

Varicella Zoster Virus

Live Vaccines

  • Live attenuated microorganisms (vaccine) provide continual

antigenic stimulation

  • Memory cell production
  • Robust immune response
  • Varivax (Varicella virus vaccine live)
  • Prevent varicella (chickenpox) in children and adolescents
  • Zostavax (Zoster vaccine live)
  • Prevent shingles in adults >50 years old
  • Do NOT give live vaccines to immunocompromised patients
  • Potential for disseminated disease
31

Zoster Vaccine Recombinant, Adjuvanted

Shingrix

  • Recombinant zoster virus surface glycoprotein E (gE) antigen
  • gE is the predominant surface protein on zoster virus
  • AS01B adjuvant (liposomal formulation)
  • Monophosphoryl lipid A (MPL) from Salmonella Minnesota
  • QS-21 saponin from Quillaja saponaria Molina
32

Zoster Vaccine Recombinant, Adjuvanted

Shingrix Age group (years)

Incidence of zoster per 1000 person-years

Efficacy Overall (≥50) 0.3 97.2% 50-59 0.3 96.6% 60-69 0.3 97.4% ≥70 0.3 97.9%

NCT01165177 (subjects ≥ 50 yrs)

Age group (years)

Incidence rate of post herpetic neuralgia per 1000 person-years

Efficacy Overall (≥70) 0.1 88.8% 70-79 0.1 93.0% ≥80 0.3 71.2%

Pooled data from study NCT01165177 (subjects ≥ 50 yrs) & NCT01165229 (subjects ≥70 yrs)

slide-9
SLIDE 9 33

Zoster Vaccine Recombinant, Adjuvanted

Phase I/II Study in Autologous Hematopoietic Cell Transplant (HCT)

  • Within 50-70 days of HCT
  • Cell-mediated immunity

(CD4(2+) T-cell frequency

  • 3- and 2-dose groups greater

than saline

  • Combined humoral and cell

mediated response

  • 3-dose > 2-dose group
  • Safety
  • 2 cases of zoster (3-dose)
  • 2 cases of zoster (saline)
  • Pain at injection site
  • Myalgias

Cell Mediated Immune Response

Stadtmauer EA. Blood. 2014;124:2921-2929

34

Zoster Vaccine Recombinant Adjuvantesd

Immunogenicity and Safety in Adults Post Renal Transplant (Zoster 041 trial)

  • 4-18 mos. after renal tx
  • 2-doses 1-2 months apart
  • Humoral and cell-mediated

response > placebo

  • Safety
  • Local AEs more common
  • General AEs similar
  • No biopsy-confirmed

rejection (1st month)

VRR(%) HZ/su Placebo

Humoral immune response

80.2% 4.2%

Cell-mediated immune response

71.4% 0% Adverse Events

HZ/su Placebo Local

87% 7.6%

General

68.7% 55.3%

MAEs

25.8% 22%

Bx proven rej. <1mo.*

0% 0%

Rejection Mos. 2-13*

4/132 7/132

Vink P. ID Week 2017, Abstract #1348. VRR=Vaccine Response Rate, HZ/Su=Herpes Zoster Subunit Adjuvanted Vaccine. MAE = AEs with medically attended visits.* Month(s) after vaccination, https://clinicaltrials.gov/ct2/show/NCT02058589 *Month(s) after vaccination.

35

Varicella Vaccines

Dose Schedule Vaccine / Indication

Dose

Schedule Cost Varivax

Varicella virus vaccine live Prevent varicella >12 months old

0.5mL

SQ Age 12-15 mos Dose 1 Age 4-6 yrs Dose 2 Age 7-18 yrs Catch-up 2nd dose* $289

Zostavax

Zoster vaccine live Prevent shingles > 50 yrs

  • ld

0.65mL

SQ Single dose $255

Shingrix

Zoster vaccine recombinant, adjuvanted Prevent shingles >50 yrs

  • ld

0.5mL

SQ Day 0 Dose 1 2-6 months later Dose 1 $336

*Centers for Disease Control and Prevention (CDC). Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1–40. 36

Varicella Zoster Vaccines

Key Points

  • Different vaccines for different indications
  • Varivax (live) to prevent chickenpox
  • Zostavax (live), Shingrix (recombinant) to prevent shingles
  • Current ACIP guidance recommends Shingrix (recombinant)
  • ver Zostavax (live) for prevention of shingles
  • NO recommendation for use in transplant recipients
  • Shingrix has been studied in renal transplant recipients
  • Preliminary data looks promising (results yet to be published)
  • ACIP guidance forthcoming based on data
slide-10
SLIDE 10 37

Thimerosal in Vaccines

  • Thimerosal is a mercury-containing compound used as a preservative
  • 25mcg mercury in 0.5mL flu vaccine
  • ~50mcg mercury in 6oz of albacore tuna*
  • No good evidence that thimerosal in vaccines is associated with autism‡

Mercury Exposure

  • Public Health Services (PHS) recommends

removal of Thimerosal from childhood vaccines

July 9, 1999

  • Manufacturers begin to phase out thimerosal in

childhood vaccines

1999

  • Manufacturing of childhood vaccines containing

thimerosal cease

2001

  • All childhood vaccines containing thimerosal are

no longer available

2003

  • Only multiple-dose vials of influenza vaccine

contain thimerosal.

2004

*http://safinacenter.org/documents/2016/09/mercury-seafood-guide-consumers-web.pdf/. ‡ Institute of Medicine. 2004. Immunization Safety Review: Vaccines and Autism. Washington, DC: The National Academies Press. 38

Useful Vaccine Resources

  • Advisory Committee on Immunization Practices (ACIP)
  • https://www.cdc.gov/vaccines/acip/index.html
  • IDSA Guidelines Vaccination of Immunocompromised Host
  • Clinical Infectious Diseases 2014;58:e44-100
  • California Immunization Registry (CAIR)
  • www.cairweb.org
  • HealthMap Vaccine Finder
  • https://vaccinefinder.org
  • Vaccine Adverse Event Reporting System (VAERS)
  • http://vaers.hhs.gov/
39

Where to Get Vaccinated?

Easy as zip code, vaccine, and click search

https://vaccinefinder.org (accessed 9/3/2018)

40

Immunizations Tab in ApeX

  • Administration history

(from ApeX)

  • Immunization Registry

(CAIRS)

  • “Recommended

Immunizations” due date

  • Immunizations report
slide-11
SLIDE 11 41

Conclusions

  • Advances in vaccine technology:
  • More effective and safe vaccines
  • New vaccines complement and extend current vaccines
  • Hepatitis B vaccine (recombinant), adjuvanted
  • Meningococcal group B vaccines
  • Zoster vaccine (recombinant), adjuvanted
  • Success stories in medicine
  • Vaccination
  • Transplantation