October 27, 2020 The Importance of Vaccines - PowerPoint Presentation

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October 27, 2020

The Importance of Vaccines

Thank you for joining us. Our program will begin at 11:30 AM Eastern.

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#vaccines

#

Inlifesciences

@Marion_Health

@IUMedSchool

@darbrow

@GregoryZimet

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October 27, 2020

The Importance of Vaccines

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PRESIDENT & CEO, BIOCROSSROADS

PATTY MARTIN

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DR. VIRGINIA CAINE

DIRECTOR & CHIEF MEDICAL OFFICER FOR MARION COUNTY DEPARTMENT OF HEALTH

DARRON R. BROWN, MD, MPH

PROFESSOR OF MEDICINE AT IU SCHOOL OF MEDICINE

GREGORY ZIMET, PHD

PROFESSOR OF PEDIATRICS, IU SCHOOL OF MEDICINE

PANEL DISCUSSION

AGENDA

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DIRECTOR & CHIEF MEDICAL OFFICER FOR MARION COUNTY DEPARTMENT OF HEALTH

DR. VIRGINIA CAINE

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FRAMEWORX ON VACCINES

Virginia A. Caine, M.D.

Director and Chief Medical Officer

Marion County Public Health Department

Associate Bicentennial Professor of Medicine

Division of Infectious Diseases

Indiana University School of Medicine

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FRAMEWORX ON VACCINES

DISCLOSURES

Speaker’s Bureau Promotional

Education-Gilead, GlaxoSmithKline

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FRAMEWORX ON VACCINES

Vaccines represent some of the most impactful public health advances seen to date

In the United States, 16 diseases are now preventable

Smallpox eradicated in 1949, Polio in 1994, Measles in 2000 and Rubella in2004

Routine immunization of children born between 19994-2018 has prevented more than 419 million illnesses

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FRAMEWORX ON VACCINES

An estimated 45,000 adults die annually from complications due to vaccine-preventable diseases.

An average of 200,00 U.S. hospitalization due to seasonal flu complications occur each year.

U.S. is home to 4% of the world’s population yet it accounts for more than 20% of both COVID-19 cases and deaths.

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Influenza Vaccination: 2020-2021

CDC. Frequently Asked Influenza (Flu) Questions: 2020-2021 Season. Available at: https://www.cdc.gov/flu/season/faq-flu-season-2020-2021.htm. Accessed 6/29/2020; CDC. Past Seasons Vaccine Effectiveness Estimates. Available at: https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html. Accessed 6/29/2020.

Vaccination to be deferred for suspected or confirmed COVID-19 to

avoid exposing healthcare personnel

Providing immunizations while maintaining

social distancing

CDC: Influenza viruses and SARS-CoV-2 will likely both be spreading in the fall and winter

Seasonal Influenza Vaccine Effectiveness, 2009-2019

Modest, variable effectiveness of influenza vaccines

underscores

need for

effective treatment options

Emphasis on

vaccination to limit hospitalization

for influenza during COVID-19 pandemic

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SENIOR VICE PRESIDENT/CHIEF DATA OFFICER, BIOCROSSROADS

DARSHAN SHAH

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Disclosures (Dr. Brown)In the past, Dr. Brown has received funds from an agreement between IUSM and Merck related to certain landmarks of vaccine development, as well as consulting fees from Merck. 

In addition to other funding agencies, Merck provides funding for Dr. Brown’s research group.Dr. Brown is a consultant for PDS, a company working to develop therapeutic HPV vaccines

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Development of the HPV vaccine: role of IUSM

Darron R. Brown, MD, MPHProfessor of Medicine, Microbiology and ImmunologyDepartment of Medicine, Division of Infectious DiseasesSimon Cancer CenterIndiana University School of Medicine

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Step 1: Understanding the virusCervical cancer is second most common malignancy in women globally, most common in poor countries

HPV (oncogenic types) are the cause of cervical cancer (zur Hausen, U. Heidelberg)Double-stranded DNA virus with protein shell (L1 major capsid protein)

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< 87.3

< 16.2

< 32.6

< 9.3

< 26.2

Cervical cancer is most common in poor countries

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Step 2: Virus-like Particles (VLPs)Scientists at U. Rochester and U. Sydney demonstrated that the L1 protein self-assembles in bacteria into virus-like particles (VLPs)

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Virus-like Particles (VLPs)HPV VLPs are immunogenic in animals (U. Rochester, IUSM and Merck)HPV VLPs elicit neutralizing antibodies

in animals and humans (IUSM and Merck)

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Step 3. Neutralizing assay (IUSM and Merck)J. Kreider

(Penn State) produced infectious HPV 11 virions in athymic miceInfectious HPV 11 added to human tissue, implanted into athymic mouse in presence of (animal or human) serum Human tissue removed from mouse 3 months laterIf no neutralizing antibody was in serum, a benign tumor containing HPV 11 would grow

However, if serum contained neutralizing antibodies against HPV 11, then no tumor grew

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Human papillomavirus type 11 neutralization in the athymic mouse xenograft system: Correlation with virus‐like particle IgG concentration

Rabbits immunized with HPV 11 virions ELISA to determine the quantity of IgG that recognized HPV 11 VLPs Rabbit sera then used in neutralization experiments in the athymic mouse xenograft system Concentration of HPV 11 L1 VLP‐specific IgG required to neutralize HPV 11 was determined (~700 to 900 ng per mL).

The study demonstrated a positive correlation between HPV 11 L1 VLP‐specific IgG and neutralization of infectious HPV 11

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Human papillomavirus type 11 (HPV-11) neutralizing antibodies in the serum and genital mucosal secretions of African green monkeys immunized with HPV-11 virus-like particles expressed in yeast

African green monkeys immunized with HPV-11 VLPs expressed in yeastHigh-titered HPV-11 VLP-specific serum IgG response elicitedSera from immunized monkeys neutralized infectious HPV 11 in the athymic mouse xenograft system. Significant levels of HPV 11-neutralizing antibodies also were observed in cervicovaginal secretions.

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Antibody response in HPV 11 VLP-vaccinated monkeys

Serum

Vaginal secretions (blood-free)

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Step 4. Clinical studies: Phase 1First human trial of any HPV vaccine done at IUSM

110 women (16 to 23 years old) given placebo or one of four doses of VLP at Day 0, Months 2 and 6All sera tested for neutralizing antibodies against HPV 11Safety data collected

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Phase 1 SafetyMinimal local reactions, dose-dependentFew systemic reactions (low-grade fever, headache)

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Phase II Studies (safety, immunogenicity, efficacy)

Monovalent HPV 16Monovalent HPV 18Quadrivalent HPV types 6, 11, 16, 18

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Phase III

Clinical Protocols

HPV types 6, 11, 16, 18 L1 VLPsMulti-center, international studies (~20,000 women)

1:1 randomization (vaccine

or placebo); day 0, months 2 and 6Examinations and specimens collected for HPV

Cytology, histology, HPV detection conducted

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Prevention of Cervical Lesions in Women 16 – 26 years (Per-protocol group)

n (quadrivalent vaccine) = 7,864; n (placebo) = 7,865

100%

95% CI

95 – 100

0 vs 71 cases

97%

95% CI

88 – 100

2 vs 63 cases

100%

95% CI

31 – 100

0 vs 7 cases

96%

95% CI

91 – 98

7 vs 170 cases

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Additional clinical studies at IUSMVaccine efficacy in malesVaccine efficacy in mid-adult women

9-valent HPV vaccine

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FDA approvals 2006-2011

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Decline of HPV infection and cervical cancer in wealthy countries14 year follow-up in 4 Nordic countiesNo cases of HPV16/18-related high-grade cervical dysplasia observed in the per-protocol effectiveness population (N=2121; 24,099 person-years of follow-up)

Vaccine effectiveness was 100% (95%CI 94 - 100) demonstrated Seropositivity rates at study conclusion >90%

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Step 5: Utilization of the vaccineAustralia: school-based, government-funded program; 92% vaccine uptake; reductions in cervical pre-cancers and cancers evidentU.S.: modest uptake, lowest HPV vaccination rates in populations with highest rates of cervical cancer

Very low vaccine uptake in poor countries where most deaths from cervical cancer occur (less than 1% in Kenya)

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Ongoing research at IUSM

Mechanisms of HPV oncogenesisDevelopment of antiviral compoundsUtilization and barriers to HPV vaccination

Natural history of HPV in young men and women in USAEpidemiology of HPV infection in Kenyan women living with HIV/AIDSCommunity-based cervical cancer eradication in Kenya: combining modern-era cancer screening (adult women) with HPV vaccination (children)

Immunological response to HPV vaccine in Kenyan children

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Prevention of HPV-Related Cancers:We have the tools – how do we finish the job?

Gregory Zimet, PhD

Department of Pediatrics

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Disclosures (Gregory Zimet, PhD)

I serve as a consultant and Advisory Board Member for Merck related to HPV vaccination I received an investigator-initiated research grant from Merck, administered through Indiana University, to study HPV vaccine series completion in IndianaI serve as an Advisory Board Member for Moderna

related to SARS-CoV-2 vaccination

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We have the tools…

But what do we need to finish the job???

We need to

overcomebarriers

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In the U.S. barriers are present at many levels

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Individual beliefs

Dangerous!

Painful!

Sex!

Too young!

STD!

My child doesn’t need it!

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Family and social group norms & beliefs

My family wouldn’t

approve.

Does it fit with my religion?What would myfriends think?

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The health care system

HCP communication

Consistency of messaging across office personnel

Standing orders?

Benchmarks?

Access

Reminder-recall systems?

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Variations in state policies and HPV vaccine series completion

76% (DC)

79% (RI)

41% (IN)

30% (MS)

77% (ND)

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National politics & policies also influence HPV vaccination rates

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Within State Variability:

Reflecting State Policy & Urban-Rural Disparities

Missed opportunities for HPV vaccination in Indiana by county2017 CHIRP data ages 11-18Green: ≤ 53%Yellow: 54% - 65%Red: ≥ 66%

Enujioke et al. Vaccine. 2020

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Social media influences

Dissemination of misinformation & fear.

Cyber attacks on HPV vaccineadvocates.

Creation of false norms.Creation & magnification

of conflict.

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All of these factors are interconnected

Logistical Challenges

Adapted from: Head et al.

Hum Vaccin

Immunother 2018;14:1626-1635.

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If we want to more parents to vaccinate their children…

Logistical Challenges

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IUPUI Center for HPV Research

Co-Directors: Gregory Zimet & Rachel KatzenellenbogenOver 40 members, including faculty, post-docs, and pre-docsRepresenting 4 Indiana universitiesAcross multiple schools and departmentsEngaged in a wide range of researchBasic scienceClinical Science

EpidemiologyBehavioral/Social SciencePublic Health Policy

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We have the biomedical tools, in particular, HPV vaccination…But we have to keep on working on beliefs, behaviors, and policy to overcome the barriers and to finish the job.

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#vaccines

#INlifesciences

@Marion_Health

@IUMedSchool

@darbrow

@GregoryZimet

VISIT

US AT

: www.biocrossroads.com

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October 27, 2020

The Importance of Vaccines