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東京大学 医科学研究所 石井健 資料

GGG+フォーラム

誰一人取り残さない持続可能社会構築のために～私たちは国境を越えて連帯できるのか？～ 日時： 2022年3月5日（日）9:00

新興感染症と新たなワクチンデザイン：
100日でワクチンを世界に届けるには
石井健（いしいけん）
東京大学 医科学研究所 感染免疫部門 ワクチン科学分野
東京大学 医科学研究所 国際ワクチンデザインセンター（VDESC)
東京大学 新世代感染症センター （UTOPIA)

COI
No financial conflict for the commercial entities.
Collaboration；Daiichi-sankyo、Shionogi, KM Biologics、 Zeria、Torii Pharma、Mandom、UMN pharma, Exorphia

Patent; US FDA, NIBIOHN, Osaka U, U Tokyo, Daiichisankyo、Zeria、Mandom
Ｆｕｎｄｉｎｇ；ＩＭＳＵＴ,ＮＩＢＩＯＨＮ, MEXT,MHLW、JSPS,ＪＳＴ、ＡＭＥＤ，ＧＨＩＴ（DNDI）

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東京大学 医科学研究所 石井健 資料

What have we learnt from COVID-19 Pandemic?

World vaccinated; doses per 100 peoples

USA today Nov 26 2021

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東京大学 医科学研究所 石井健 資料

USA today Nov 26 2021

USA today Nov 26 20213東京大学 医科学研究所 石井健 資料

2023/3/4

Why we need to work on Vaccine R&D?

WHO’s vision on immunization 2021-2030‘A global strategy to leave no one behind’42023/3/4

東京大学 医科学研究所 石井健 資料

Vaccine-preventable diseases (VPD)=27Herpes zoster

InfluenzaMumpsTyphoid

Pertussis

Hepatitis A

Anthrax
Cholera2

Smallpox and vaccinia

Yellow feverRabies

Tetanus

Varicella

Japanese encephalitis「Vaccination is the most effective method ofpreventing infectious diseases」
Diphtheria

Haemophilus influenzae type b

Polio

Pneumococcal
Tick-borne
encephalitis3

Rubella
Hepatitis B
Measles

Human papillomavirus
Lyme disease

Meningococcal

Tuberculosis
Rotavirus

1. Centers for Disease Control and Prevention. Vaccines and preventable diseases. Available at: http://www.cdc.gov/vaccines/vpd-vac/default.htm (accessed November2011); 2. Roush S, et al. Centers for Disease Control and Prevention. MMWR 1999; 48:243–248. 3. Centers for Disease Control and Prevention. Special pathogens branch.
Available at: http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/TBE.htm (accessed November 2011).

• Priority pathogens and diseases • R&D Blueprint priority diseases
for low- and middle-income(April 20202)
1
countries (PDVAC 2019 )• COVID-19• Enterotoxigenic E. coli
• Gonococcal disease• Group A streptococcus• Group B streptococcus• Herpes Simplex Virus• Human Immunodeficiency Virus• Influenza (nextgeneration vaccines)• Malaria• Respiratory Syncytial Virus• Shigella• M. Tuberculosis• Crimean-Congo haemorrhagic fever• Ebola virus disease• Marburg virus disease• Lassa fever• Middle East Respiratory Syndrome• Severe Acute Respiratory Syndrome• Nipah and henipavirus diseases• Rift Valley fever• Zika• “Disease X”, a pathogen currently
unknown to cause human disease1https://www.who.int/publications/m/item/pdvac-list-of-participants-20192https://www.who.int/activities/prioritizing-diseases-for-research-and-development-in-emergency-contexts52023/3/4

東京大学 医科学研究所 石井健 資料<potential and existing threats>
WHOZika

USTularemia
Small pox

Hendra virus
Crimean-Congo
haemorrhagic fever(CCHF)

SARS

AMR

Ebola

Anthrax
Arena virus
Yersinia
pestisDenguevirus
Clostridium
botulinum

Marburg
Lassa
fever
Rift Valley
fever

hantavirus

What else needed?

MERS

MDR tuberculosis

Nipahvirus

MalariaHIV
HCV HBV
CMV HSVSFTS
HTLV

Disease X

ChikungunyaFever
Q fever

UK

CEPI

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東京大学 医科学研究所 石井健 資料

WHO’s mission for local immunization programs in global scale
UHC (Universal Health Coverage)

ＷＨＯ

Immunization opportunities in all life courses

Please imagine and plan precisely TPP (Target Product Profile) from the beginning

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東京大学 医科学研究所 石井健 資料

Vaccines against non-communicable diseases
Indication

Target antigen

Allergy

Allergen

Atherosclerosis

ox-LDL, ApoB-100, CETP

Alzheimer’s disease

Amyloid-β

CancerTumor antigen

DiabetesIL-1βHypertension

Angiotensin I/II

ObesityGhrelin

Rheumatoid arthritis

TNF-α

Systemic lupus erythematosus

IFN-αAging??

What we can do for Vaccine R&D?

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東京大学 医科学研究所 石井健 資料

Vaccine Yattafuri
Washington post July 2021 before Tokyo olympic

Any COVID-19 vaccine made in Japan?
Yes, but not yet ready(listed below are at Ph2 or later stage)

Company

Type of vaccine

StatusAnGes/Osaka U

Plasmid DNA

Ph2/3-stopped

KM Biologics/U Tokyo

Attenuated Virus

Ph3

Shionogi/NIID/U Tokyo

rProtein + Adjuvant

Ph3

Daichi Sankyo/U Tokyo

LNP-mRNA

Ph3

Mitsubishi Tanabe

Plant based VLP

Ph2/3

followed byBIKEN, ID-pharma, VLPt, Nobel Pharma, Hanavax, Elixirgen,
Astra Zeneca, Novavax/Takeda (designed by UK, US, respectively = Made with Japan)

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東京大学 医科学研究所 石井健 資料

2021 UK

2023 Hiroshima Japan

2022 Germany

What is 100 days mission?
During COVID19, it took

326 days

Total number of deaths due to the
COVID-19 pandemic, 2020 (Mn)

1.5

1

Jan 11: WHO receives
genetic sequencing of thenovel coronavirus

for development
0.5to EUA bystringent

0Jan 11

Dec 2: first green
light forPfizer/BioNTech’s
vaccine by the UK

Jan 30: WHO
declares PHEIC

Feb 29regulatory

Days after sequence
publishedauthority# Totaldeaths(Mn)Mar 31

Apr 30May 31

Jun 30100Ambition0.2

Jul 31

Aug 30

Oct 31

Nov 30Dec 5326
Fastest COVID-19 developer

1.6102023/3/4

東京大学 医科学研究所 石井健 資料

100 days mission seems impossible; Is this dream?

Alert trigger
Example metrics:•••

100days

Human-to-human transmission
confirmed, with failure of typicalcontrol measures
Unusual high # severe disease cases
or deaths (e.g., at hospitals withincountry / area)
New infectious diseases pathogen
identified as causative agent

Vaccine available for use
Vaccine made available for use by
respective authorities
e.g., vaccine deployment for publichealth intervention to control anoutbreak in agreement withregulatory authorities

We acknowledge this goalis incredibly ambitious
and have established it asa north star, recognizingthat with vision andcollaboration, greatthings are possible

How we can do for Vaccine R&D?

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東京大学 医科学研究所 石井健 資料

AMED-SCARDA world-leading vaccine R&D centers
Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response

AMED-SCARDA world-leading vaccine R&D centers launched in Nov 2022
Strategic Center of Biomedical Advanced Vaccine Research and Development for Preparedness and Response

The University of TokyoUTIAS with Kavli, IRCN

utopiaFlagship Center
Prof. Kawaoka

Hokkaido University

Synergy Prof. SawaCenters

Supportinstitutions

Chiba University
Prof. Kiyono

IMSUT hospital, BBJ
3 departments and 7 centers

Osaka University
Prof. Akira

Nagasaki University
Prof. Morita• Small Animal Supply and animal model development center ： Central Institute forExperimental Animals• Non-human primate Supply and experiment centers： Shiga University of MedicalScience, National Institutes of Biomedical Innovation, Health and Nutrition• Immunological analysis centers ： Kyoto University, RIKEN• Genome data analysis center ： The University of Tokyo (BBJ/IMSUT)
2412

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東京大学 医科学研究所 石井健 資料

UTOPIA Organization
Director

The UTOPIA Center

Scientific Advisory Board

Y. Kawaoka

AdviseAdministrativeDirector

Deputy Director

Deputy Director

Deputy Director

J. Inoue

K. Ishii

Y. Kawaguchi

M Kikuchi

Administrative office

Deputy Director

Y SetoProject Management Office

Departments
Vaccine& Immunology

Clinical Research&Trials

PMPM
Synergy Inst
Hokkaido U, Chiba U,
Osaka U. Nagasaki U

H. Yotsuyanagi, Co-PIs

K. Ishii, Co-PIs,Industries

Translational
Research

Microbiology

Y. Kawaguchi, Co-PIs

M Kikuchi, Co-PIs

International
Collaborations

Multidisciplinary
ResearchK. Tsumoto, Co-PIs

Med School PM
Hospital
IMSUT
Hospital

PMSupport Institutes
CIEA, NIBIOHN, Shiga U
Kyoto U, RIKEN, BBJ/UT25C. Coban, Co-PIs

UTOPIA’s global network
Collaborations
Inst. Pasteur
U Wisconsin
中国拠点 Global public-private partnership between

NIH
Sent Jude CDC

Children’s Hosp.
Mt Sinai Med Sch.

Washington U
Penn U
Emory U
La Jolla Inst.

U North Carolina

universities, vaccine manufacturers andgovernment of each countries

Japanese gov’
AMED SCARDA

National Inst.
NCGM• The keys for the success are;NIID• Sharing information
Synergy Inst.
• Sharing reagents
Hokkaido U. Chiba U.
• Sharing results
Osaka U. , Nagasaki U.
• Sharing credits Daiichi Sankyo

Harvard U
U Marburg
Melbourne U
U Cambridge
Imperial C London
China CDC
Harvin Vet. Res. Inst.
U Sierra Leone

Industries

Shionogi
KM Biologics
CytivaSysmex
NECSupport Inst.
RIKEN Kyoto U
NIBIOHN Shiga Med Col.
CIEA
Genome Ctr, U TOkyo

Promote a new dimension of infectious disease/vaccine immunology research with an eye on
the way out, by developing multidisciplinary fusion on an unprecedented scale in industry,
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東京大学 医科学研究所 石井健 資料

Japan academia teams up for 100 days mission
A top level support team was established by the AMED SCARDA support
for the preclinical development of novel vaccines against novel infectious organisms
Int. Vaccine Design Center
BSL3 facility

Res. Center for
Drug and Vaccine Development.
BSL3 facility

Tsukuba Primate Res. Ctr.
BSL3 facility

Collaborations Inst. Med. Sci. U Tokyo

Natiional Inst. Infecious D.
(NIID)

Nat. Inst. Biomedical Innov.
(NIBIOHN)SCARDAinstitutes(IMSUT)

Unknownpathogens

Novel Vaccines
CholSDGs

OJT

LipidmRNA

Large animals

Small animals

PEGCROs

LNP-mRNA

Pathogens identified➡ vaccine design➡ CMC ➡ Immunogenicity（humoral, cellular）➡ challenge test

IMSUT renewed its vaccine R&D center toward vaccine design 2022-

International Vaccine Design Center (VDesC)

At 3F Bldg 4 IMSUT, Shirokanedai, Minato, Tokyo

Human immune-profiling team

New dimensional vaccine design team
Adjuvant Innovation

MucosalImmunology

Immunology
andGenomics

SystemsImmunology

HumanImmunology

InfectionImmunology

Vaccineengineering

Immunology
using Machinelearning, deeplearning and AI

Immunologicalanalysis ofhuman clinicalstudy

Reversetranslational
immunology ofinfection

Engineeringof vaccine
antigen andantibody

Innovation of adjuvant
module for the optimal
vaccination

Mucosal approachof vaccine
immunology

Immunology
using genomic
approach

Cevayir Coban

Kouhei
TsumotoKen J. Ishii
Kouji Kobiyama
Jun Kunisawa

KohtaroFujihashi

Anavaj
Sakuntabhai

Kei Sato

Patient’s
sampleKen J. Ishii
NorikoSorimachi

Multi-dimensional immunomics
by single cell/particle analysis

Vaccinee’ssample

Identification of the protective
antigen for the target diseases

Shooting the Achilles heel of target
antigen/immune pathway

Machine learning todeep learning to AI

Experimental
validation forPOC

New dimensional
vaccine design
Adjuvant
Delivery/Modality
Antigen

The optimized module for theprompt vaccine development

Global network for human immunomics

Oxford U, Pasteur Inst.
Erasmus Med Ctr, US NIH/FDA
UCSD, La Jolla Immunol. Inst
NUS, IVI (Korea),Noguchi Inst.

Global networking and collaboration
for the optimal PPP14

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東京大学 医科学研究所 石井健 資料

AI assisted human immunomics
Issues -> solution○ Human immune responses are so diverse that we need single cell-based, and AI-supported, multidimensional immunomics to identify to find the Achilles heal of the pathogen and smarter vaccine design

What we do

Human Immuno-profiling

We will identify the Achiles heal (antigen) and an arrow to let off at it
Samples from
infected patients

Multiparametricimmuno-profiling at
single cell level

Samples fromthe vaccinees

Multi-omics ofimmune cells

Multidimensional
Immunomics

From machinelearning to deeplearning to AI

New dimensional
vaccine designExperimentalapproach
using animal models

Clinical data (disease score,Biomedical parameters)
Medical genome data

Vaccine design with 3 modules
Issues and solution
In order to make destructive innovation for the rapid, and more precise and efficient vaccine development, wewill take new strategy to split the vaccine elements into ‘modules’ into 1-new modality of antigen expression, 2adjuvant and 3-delivery system to design an arrow (vaccine) to shoot the Achilles heal of the target pathogen

What we do

New dimensional vaccine design

From human immunoprofiling

Design vaccine letting off an arrow(optimal immune response) to the Achiles’s heal
①Antigen-modules

AI-assisted
immuno-mics to findan arrow and theAchilles’s heal ofpathogen

Innate immunity Adaptive immunity（to define specificity of vaccine effect）

Platforms using virus, bacterial,protein, peptide, RNA, DNA②Adjuvant-modules
Experimental
assessment byanimal models

by splitting the vaccine elements
into 3 modules（to define direction of vaccine effect）
Platforms using nano-particle, lipid,nucleic acids, protein and others③Delivery-modules(to define the tissue of vaccine effect)
Platforms using syringe/needle, oral,nasal-, skin-mediated delivery

Vaccine antigen
specific immune
responses

inflammation

minVaccine

hours

months-years
HumoralImmunity

Innate immune
receptors

Adjuvant

Delivery system
Antigendays

Cytokines
e.t.c

Ｂ cells

AntigenT cellspresenting
MHC TCR
Cells(APC) -peptide
Cellularimmunity

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東京大学 医科学研究所 石井健 資料

Ethicsin Vaccine Science

Vaccine hesitancy
It was and is getting global issue,
but still is key and critical matters forvaccine confidence and acceptanceEBioMedicine 12 (2016) 295–301

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2023/3/4

Lessons from the past
“Le Chaudron et la Lancette “ Yves-Marie Bercé‘The French historian Yves-Marie Bercé, is the author of a bookentitled Le Chaudron et la Lancette (right) which tells how theEnglishman Edward Jenner’s discovery of a treatment forsmallpox in the summer of 1798 then spread to the rest ofEurope.
To quote: "The news spread through Europe like wildfire.
However, this was a time when the continent was in a state ofwar; the seas were in the hands of pirates and roads were cut off
by armies. Despite all these obstacles, the vaccine against
smallpox found ways of getting through. Within a few years, andin all countries, not only were the professors in the universities
aware of the discovery, but so too were ordinary doctors inprivate practices, despite not being in the main run of intellectualideas, and they were able to make the vaccine available in theirlocalities, and, furthermore, with a high degree of efficiency.“More by Kenzaburo Oe
http://mondediplo.com/1998/12/11kenzaburo

Manga Education for Vaccine science,microbiology and Immunology seems far
better than anything

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東京大学 医科学研究所 石井健 資料

THANK YOU!
Vaccineワク
チン
Once in the lifetime chance

Lab HPTHANKYOU!

DonatevDESC

一期一会 ICHI GO ICHI E ; Live every day as though it were last.

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東京大学 医科学研究所 石井健 資料

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