10. Pathophysiology
IMOJEV Seminar Slides | 10
Diagana M, Preux P M , Dumas M. Japanese encephalitis revisited. J Neurol Sci. 2007. 262:165-70
Bite from an infected
Culex mosquito
Nervous system
Transient viremia
follows
Cerebral tissue inflammation
Virus multiplies in regional
lymph nodes
TW.JEV.16.05.05
24. SPTW.IMOJ.19.06.0034 (06/19)
國人日本腦炎疫苗接種史及抗體陽性率
| 24Chang YK et., Epidemiological Features of Japanese Encephalitis in Taiwan from 2000 to 2014. Am. J. Trop. Med. Hyg., 2017, 96(2) ; 382-388.
• 45%患者完成4劑不活性日本腦炎疫苗的接種
• 抗體恐隨時間下降,成人可考慮補接種日本腦炎疫苗
2000-2014年 379例台灣日本腦炎確診病例疫苗接種紀錄
30. Recombinant Vaccine Technology*
Recombination: A Process of Attenuation
| 30
Attenuated vaccine
strain SA14-14-2 JEV
Attenuated vaccine
strain 17D yellow fever
Recombinant chimeric
JE vaccine virus
induces long-lasting and well
controlled immunogenic
response after immunisation
triggers a neutralising
antibody response against the
JE envelope
*Recombinant vaccine technology in the past use to produce Engerix-B® , HB Vax II, Euvax-B, Infanrix ® -Hexa, Rotateq ® , Cervarix ® , Gardasil ® (HPV)
> 75 yr use
> 500M dose
> 25 yr use
> 90M dose/yr
Considered an ideal live vector for
development of new vaccines
Chambers TJ et al. J Virol 1999
SPTW.IMOJ.19.04.0026 (05/19)
31. ● Seroprotection rates at D14 post
single injection show that JE-CV
elicits a rapid immune response
● 93.6% (CI: 90.5, 96.0)
● At Day 14 post single injection
GMTs (homologous testing) were:
● 312 (CI: 255-382)
● At Day 28 GMTs were:
● 1392 (CI: 1156, 1674)
| 31
Torresi J, McCarthy K, Feroldi E, Méric C. Immunogenicity, safety
and tolerability in adults of a new single-dose, live-attenuated
vaccine against Japanese encephalitis: Randomised controlled
phase 3 trials. Vaccine. 2010; 28: 7993-8000.
93,6%
99,1%
312
1392
1
10
100
1000
10000
0
10
20
30
40
50
60
70
80
90
100
D14 D28
% seroprotected GMT's
Immunogenicity adults (non endemic)
Early response within 14 days with IMOJEV®
Short term immunogenicity in adults
1. Early response post Imojev®
SPTW.IMOJ.19.04.0026 (05/19)
32. Short term Immunogenicity in adults
2. IMOJEV® vs JE-VAX® (MBDV): Seroprotection*
● Double-blind, randomised, controlled
● Multicentric : 5 centers Australia, 5 USA
● Number of subjects: 820
● 410 received 2 doses placebo and single
dose JE-CV
● 410 received 3 doses JE-VAX® (D0,D7,D30)
● Immunogenicity
● Primary criteria: 30 days post JE-CV or 30
days after third dose of JE-VAX®
● Secondary criteria
• Immunogenicity at D14 post JE-CV
• GMTs evaluation
| 32
One dose of JE-CV is non-inferior
to 3 doses JE-VAX®
99,1%
95,1%
50
60
70
80
90
100
IMOJEV® JE-VAX®
% seroprotected
*Sero-protective threshold is defined as a PRNT titer ≥ 10; Hombach et
al vaccine 2005
Torresi J, McCarthy K, Feroldi E, Méric C. Immunogenicity, safety
and tolerability in adults of a new single-dose, live-attenuated
vaccine against Japanese encephalitis: Randomised controlled
phase 3 trials. Vaccine. 2010; 28: 7993-8000.
Study summary
SPTW.IMOJ.19.04.0026 (05/19)
33. Desai et al. Vaccine 2012
● Estimated median duration of seroprotection: 21.3 years
34
Desai K. Modelling the long-term persistence of neutralizing antibody in adults after one dose of live attenuated Japanese encephalitis
chimeric virus vaccineVaccine. 2012; 30: 2510-2515.
Long-term Immunogenicity of Imojev in Adults
Modeling
SPTW.IMOJ.19.04.0026 (05/19)
54. 麻疹病毒
• 單股RNA病毒
• Family (科): Paramyxoviridae
• Genus (屬): Morbillivirus
• Species (種): measles
• 可分成
– 8個 clades (品系): A-H
– 23個 genotypes (基因型)
USCDC PHIL Photo ID# 8429
55
55. Case Demo
• 1-year-1- month girl , Twin A
• 10/30-2/28 lived in Guangzhou
• Contact history:
– twin B had measles diagnosed in Guangzhou 2 weeks
ago
• Presented with
– High grade fever for 6 days
– Cough, rhinorrhea, no conjunctivitis
– Generalized skin rashes at 4th day of fever
– Neck trunk face