Imojev Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of action: The vaccine is a live attenuated virus. Following administration, the virus replicates locally and elicits neutralising antibodies and cell-mediated immune responses that are specific to the Japanese encephalitis virus. Available results indicate that protection is mainly mediated by neutralising antibodies.
In nonclinical studies, all animals that received a single dose of the vaccine developed specific neutralising antibodies against Japanese encephalitis virus and were protected against infection by a virulent Japanese encephalitis virus experimental challenge.
Immunogenicity: Passive antibody transfer results in a small animal model indicate that protection is mediated by neutralising antibodies and that the threshold for protection is a plaque reduction neutralisation titer of 1:10.
Immunogenicity data in adult population: A single dose administration of IMOJEV is as immunogenic as a three-dose regimen of an inactivated Japanese encephalitis comparator vaccine administered in adults 18 years of age and over.
A seroprotective level of antibodies is generally reached 14 days after vaccination.
In a randomised comparative phase III trial, 410 subjects over 18 years of age received a single dose of not less than 4.0 log PFU/dose of 0.5 mL of IMOJEV and 410 subjects over 18 years of age received a three-dose regimen of 1 mL of an inactivated Japanese encephalitis comparator vaccine.
Thirty days after vaccination, the seroprotection rates for the subjects who received IMOJEV were more than 99% when measured against the homologous virus strain. These results are non inferior to those observed after the three dose regimen of the inactivated Japanese encephalitis comparator vaccine.
Fourteen days after a single dose of IMOJEV, approximately 93% of the vaccinees showed seroprotective levels of neutralising antibodies.
In a long-term follow-up assessment in a randomised control phase II trial, 97.6% (95% CI, 93.3; 98.8) of subjects showed seroprotective levels six months after a single administration of IMOJEV.
Long-term immunogenicity data up month 60 are presented as Kaplan-Meier estimates the probability of being still seroprotected 60 months after vaccination for those who were seroprotected at six months is 86.8%.
Immunogenicity data in paediatric populations: Primary Vaccination: A seroprotective level of antibodies is generally reached 28 days after vaccination.
A single dose administration of IMOJEV in 2 randomised trials in 1,231 toddlers (12 to 24 months) not previously immunized with a Japanese encephalitis vaccine shows that approximately 95% of subjects seroconverted and are seroprotected (neutralizing antibody level above the threshold of protection) after 28 days. A single dose administration of IMOJEV in a randomised comparative phase III trial in infants and toddlers (9 to 18 months) (N=126) not previously immunized with a Japanese encephalitis vaccine showed that more than 99% of individuals seroconverted and were seroprotected after 28 days.
The persistence of seroprotection was assessed in a Phase II and a Phase III trials in toddlers (12 to 24 months).
In the phase II trial, approximately 65% of toddlers who did not receive any Japanese encephalitis vaccine before the single dose administration of IMOJEV were shown to still have seroprotective antibody level 5 years after the vaccination (N = 151).
Table 1 shows the immune response up to 5 years after vaccination with a single dose of IMOJEV (see Table 1).


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In the Phase III trial, approximately 75% of toddlers who did not receive any Japanese encephalitis vaccine before the single dose administration of IMOJEV were shown to still have seroprotective antibody levels 5 years after the vaccination (N=478). All the toddlers included in this trial with serological data available 28 days after vaccination were seroprotected at this time point.
Table 2 shows the immune response against the homologous virus, up to 5 years after vaccination with a single dose of IMOJEV (see Table 2).


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In another phase III trial in infants and toddlers (9 to 18 months) not previously immunized with a Japanese encephalitis vaccine, approximately 88% of individuals were still seroprotected 1 year after the single dose administration of IMOJEV.
Booster: Booster dose of IMOJEV after primary vaccination with IMOJEV: In a phase III trial, a second dose (booster dose) of IMOJEV was administered in children (36 to 42 months) (N = 340) 24 months after primary vaccination with IMOJEV. A control group of children (36 to 42 months) (N = 39) who never received a Japanese encephalitis vaccine, received IMOJEV for the first time to characterize the primary response to IMOJEV.
The Geometric Mean Titer (GMT) increased by nearly 6 fold from Day 0 to Day 7 after the administration of IMOJEV to subjects previously vaccinated. By comparison, the GMT did not increase the control group, thus demonstrating an anamnestic response in the booster group. The GMT increased by nearly 57 fold from Day 0 to Day 28 in the booster group.
100% of children previously vaccinated with IMOJEV showed seroprotective antibody levels 28 days after the administration of the booster dose 24 months after primary vaccination.
Table 3 shows the immune response against the homologous virus strain, 7 and 28 days after administration of a booster dose of IMOJEV (see Table 3).


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In a Phase III trial, a second dose (booster dose) of IMOJEV was administered in children (18 to 36 months of age) (N=53) between 12 and 18 months after primary vaccination with IMOJEV.
The GMT increased by nearly 62 fold from Day 0 to Day 28 in the booster group.
100% of children previously vaccinated with IMOJEV showed seroprotective antibody titers 28 days after the administration of the booster dose between 12 and 18 months after primary vaccination.
In the long-term follow-up assessment of the phase III trial, nearly all children (98.2%) who received the booster dose of IMOJEV 24 months after primary vaccination were shown to still have seroprotective antibody levels 4 years after the vaccination.
Table 4 shows the immune response up to 4 years after vaccination with a booster dose of IMOJEV (see Table 4).


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Booster vaccination with IMOJEV after the administration of an inactivated JE vaccine as a primary immunization.
In a Phase II trial, IMOJEV was administered to children (2 to 5 years) (N = 97) 6 to 38 months after a two-dose primary vaccination with an inactivated Japanese encephalitis vaccine (mouse brain-derived Japanese encephalitis vaccine).
The GMT increased by nearly 59 fold from Day 0 to Day 28. Approximately 93% of subjects seroconverted and they were all seroprotected (titer above a threshold considered as protective) 28 days after the administration of IMOJEV.
Table 5 shows the immune response 28 days after the administration of a booster dose of IMOJEV after a primary vaccination with an inactivated JE vaccine (see Table 5).


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In the long-term follow up assessment of the phase II trial, nearly all children (97.5%) who received the booster dose of IMOJEV 6 to 38 months after the two-dose primary vaccination with the inactivated Japanese encephalitis vaccine were shown to still have seroprotective antibody levels 3 years after the vaccination.
Table 6 shows the immune response up to 5 years after the administration of a booster dose of IMOJEV after a primary vaccination with an inactivated JE vaccine (see Table 6).


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Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non clinical data revealed no special hazard for humans based on animal studies.