vaccine strategic reserve for east asia: what we have and what we need

Vaccine strategic reserve for East Asia; what we have and what we need

Taro KokuhoNational Institute of Animal Health, NARO, Japan

Maintaining Global Freedom from Rinderpest, FAO, Rome, Italy

20-22/Jan/2016

改めて学ぶワクチン学― 牛疫撲滅の歴史を例にして―

動物衛生研究所動物疾病対策センター製造科　　　　　　　　　　国保健浩

平成２７年度ウイルス講習会

平成２７年１０月１３日

Brief introduction of National Institute of Animal Health

Fact

Headquarters & Main Research Center (Tsukuba)RPHF; category B

Exotic Disease Research Facility (Tokyo)RPHF; category A

South Branch for Tropical Disease Research

North Branch for Dairy Sciences

- Member institute of agricultural research organization, NARO- Only one institute for animal health research in Japan (established in 1904)- R&D, education & training, diagnosis as national/international reference, natural resource bank, biologics manufacturing- 175 research staff & 60 administration personnel

Food Hygiene

Public Health Sector Livestock hygiene center: 166

Vets: 2,084

16 Veterinary

Schools

Disease Control and Biologics

Administration

Research & Education

Veterinary officers of local government (47 prefectures)

GOJ

Ministry of Public Health Labor and Welfare

(MHLW)

Ministry of Education, Culture, Sports, Science (and Technology

(MEXT)

MAFF

Agriculture Sector

Agriculture, Forestry and

Fisheries Research Council

Slaughterhouse: 112Vets: 2,003 Commercial farms

- Audit- Inspection- Surveillance- Consultation

Clinicaldoctors

NIAHTechnical advice

Education and training

NARO

Food Safety and Consumer Affairs

Bureau

NIAH in Animal Hygiene Management of Japan





Short history of rinderpest in Japan




The initial outbreak of rinderpest in Japan was recorded in 1636.

The outbreak continuously happened and increased with the import of live cattle from the continent.

The first preventive measure for reinderpest was implemented in 1878.


Dr. Kakizaki developed world’s 1st inactivated rinderpest vaccine in 1917.


The production of anti-rinderpest antisera had been started in 1897. The new production factory was build in Fusan, Korea in 1910.

The last clinical case in Japan was reported in 1920.


Ako branch of the National Institute of Animal Health was settled in 1952. The current vaccine strain, LA-AKO, was established from L strain at Ako branch in 1957.

Dr. Nakamura established rabbit attenuated live vaccine, L (or Nakamura III) strain, from the pathogenic field strain, Fusan (B), in 1938.

- L strain is still pathogenic to highly susceptible cattle breeds, such as Japanese black, Korean yellow.

Then, he established chick embryo attenuated lapinized live vaccine, LA strain, in 1940.

- Those cattle were immunized with L strain vaccine in combination with anti-RP antiserum.





Production of LA-AKO vaccine for rinderpest in NIAH

Regulation for veterinary vaccine manufacturing

GMP division GQP division

Factory A CB

Materials

Sales division

User

GVP division

NationalAssay

Laboratory

Validation/evaluation

Approval/certificationFollow-up/recall

distribution

Materials Materials

- RP vaccine is stored for emergent use only.

GMP facility of NIAH for vaccine manufacturing

- Currently, 12 biological products are produced by 20 staff at this facility.





Biological property of LA-AKO vaccine

平成２７年１０月１３日Pedigree of RP vaccine of Japan

- Passage history of the currently used seed of LA-AKO; 456 and 29 passages in chick embryo and in rabbit, respectively

- No clinical sign other than hyperthermia is observed even inhighly sensitive breeds such as Japanese black, Korean yellow.- Biomarkers facilitate easy differentiation of LA-AKO from other field strains.

Takamatsu, Terui, Kokuho. Genome A (2015)

- Over all similarity of LA-AKO with its parental strain, Nakamura III, and most widely used vaccine strain, RBOK, is 97% and 88% at nucleotide level, respectively.

Phylogenic tree of RP strains

- Several SNPs may exist in viral genome of LA-AKO used for RP vaccine production.



Possibility for extended storage of LA-AKO strain vaccine

改めて学ぶワクチン学




Conclusion

- LA-AKO strain is a safe vaccine strain, especially for highly susceptible Asian cattle breeds.- Our vaccine may be active after long term storage at an appropriate temperature.- We are currently producing 100,000 doses of RP vaccine every two years under the control of national laws and regulations.

- We need to discuss possible vaccination strategy and strategic storage and global distribution of RP vaccines for unpredictable outbreak.

We have submitted a revised version of OIE terrestrial manual (Chapter 2.1.15, section C. REQUIREMENTS FOR VACCINES) for discussion in the general meeting 2016.

Thank you

Merci

有り

難う

ござ

いま

した

Gracias謝謝

The Eradication of Riderpest from Africa, AU-IBAR (2011)

80 年代の牛疫による壊滅的被害

強毒牛疫株（釜山株）による感染実験

Vero cells, LA-AKO inoculated

Day1 Day2