Peptide Vaccine for
Infectious Disease
M2 Toyama
2020/5/11

Contents

1. Introduction
2. Example of Peptide Vaccine

3. Peptide Vaccine for SARS-CoV-2
4. Summary2

Vaccine- Vaccines stimulate immune
system and prevent infectious
disease.
- Vaccination prevents 2~3
million death every year.
- Development of somevaccines remains challenging.
(e.g. HIV, influenza virus)
Nat. Med., 2005, 11, 45.
Nat. Rev. Immunol., 2006, 6, 148.

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T-cell Stimulation- Antigen is presented onMHCs.
- MHC-I : 8-11 residues- MHC-II : 11-30 residues- TCR recognizes theepitope and activate
immune response.

Chem. Rev., 2020, 120, 3210.

4

B-cell Stimulation

Chem. Rev., 2020, 120, 3210.

5

Types of Vaccines

J. Invest. Dermatol., 2010, 130, 352.

6

Considerations of Peptide Vaccine
VLP- Neutralizing epitope should beadopted.

- Peptide is conjugated to carrier
protein or presented in particle(VLP or nanoparticle)
HCV peptide C1- Fixing epitope conformation isnecessary.
- Injection with adjuvants issometimes effective.
J. Virol. 2017, 91, No. e01032−17.
Inmunologia, 2013, 32, 102.

7

Contents

1. Introduction
2. Example of Peptide Vaccine

3. Peptide Vaccine for SARS-CoV-2
4. Summary8

Target: Influenza Virus- ~10 million people are
infected every year in Japan.
- Very rapid mutation- Hemagglutinin (HA) is themajor target of vaccine.

Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 18979.
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LAH-KLH Peptide- mAb 12D1 reacts with LAH ofHA2.
- LAH-KLH was synthesized andused as a peptide vaccine.
Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 18979.
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Activity of Peptide Vaccine

Proc. Natl. Acad. Sci. U. S. A., 2010, 107, 18979.
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Target: HIV- After long incubation (~10 years),
immune system is destroyed.
- 30,000 patients in Japan- There exist many types of virus.
- Non-human animals do not catchvirus.

PLoS One, 2007, 2, e984.

12Retrosynthetic StudyACS Chem. Biol., 2017, 12, 1566.

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Synthesized Peptide (1st Generation)

ACS Chem. Biol., 2017, 12, 1566.

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Synthesized Peptide (1st Generation)

ACS Chem. Biol., 2017, 12, 1566.

15

ELISA Study
PGT128

PGT121

10-1074

ACS Chem. Biol., 2017, 12, 1566.

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Synthesized Peptide (2nd Generation)

Cell Chem Biol, 2017, 24, 1513.

17

Activity of 2nd Generation Peptide Vaccine

Cell Chem Biol, 2017, 24, 1513.

18

Antisera Binding to Various V3 mimic

Cell Chem Biol, 2017, 24, 1513.

19

Synthesized Peptide (3rd Generation)

ACS Cent Sci, 2018, 4, 582.

20

Activity of 3ｒｄ Generation Peptide Vaccine

ACS Cent Sci, 2018, 4, 582.

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Target: Respiratory Syncytial Virus (RSV)- Infection mainly in infants- Symptoms include
bronchiolitis and pneumonia.

- Cause of 6.7% of all deathsin children of ages 1 monthto 1 year- Neutralizing antibody Paliand Mota
Lancet, 2010, 375, 1545.
Nature, 2014, 507, 201.

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Computational Method

Fold From Loops (FFL) procedure(1) Selection of the functional motif(2) Folding to build diverse conformation(3) Sequence design and structural relaxation(4) Filtering and human guided optimization
Nature, 2014, 507, 201.

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Structural Characterization of FFL-001

Nature, 2014, 507, 201.

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Serological Analysis

Nature, 2014, 507, 201.

25

Analysis of Produced mAbs

Nature, 2014, 507, 201.

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Contents

1. Introduction
2. Example of Peptide Vaccine

3. Peptide Vaccine for SARS-CoV-2
4. Summary27

Target: SARS-CoV-2- More than xx cases andyy deaths in the world(2020/5/10)- S protein binds to human
ACE2 receptor to cause
infection.
- DNA, mRNA, inactivatedvirus vaccines are underdevelopment.

Acta Pharm Sin B, , DOI:10.1016/j.apsb.2020.02.008.

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Latest Vaccine Development

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Peptide Vaccine for SARS-CoVClin. Chem., 2004, 50, 1036.

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Epitope Conservation among Coronaviruses

J. Med. Virol., 2020, 92, 495. 31

Computational Peptide Vaccine Design

J. Med. Virol., , DOI:10.1002/jmv.25736.

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Contents

1. Introduction
2. Example of Peptide Vaccine

3. Peptide Vaccine for SARS-CoV-2
4. Summary
33

Summary- Vaccines rescue millions of people every year.
- Peptide vaccines are less allergenic.
- LAH of HA2 is effective as immunogenic epitope. (influenza virus)- 3 component peptide induces antibody against gp120. (HIV)-Computationally designed peptide induce better neutralizing
antibodies than existing antibody drug. (RSV)- Vaccine study of SARS-CoV may help develop vaccine against
SARS-CoV-2.
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