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Correlation of protection against Japanese encephalitis virus and JE vaccine (IXIARO ®) induced neutralizing antibody titers
by
Van Gessel, Yvonne
,
Dewasthaly, Shailesh
,
Tungtaeng, Anchalee
in
Allergy and Immunology
,
Animals
,
Antibodies, Neutralizing - blood
2011
Immune sera from volunteers vaccinated in a blinded Phase 3 clinical trial with JE-VAX
® and a new Japanese encephalitis virus (JEV) vaccine (IC51 or IXIARO), were tested for the ability to protect mice against lethal JEV challenge. Sera from IXIARO vaccinated subjects were pooled into four batches based on neutralizing antibody measured by plaque reduction neutralization test (PRNT
50 titer): high (∼200), medium (∼40–50), low (∼20) and negative (<10). Pooled sera from JE-VAX
® vaccinated subjects (PRNT
50 titer
∼
55) and pooled JEV antibody negative pre-vaccination sera were used as controls. Groups of ten 6- to 7-week-old female ICR mice were injected intraperitoneally with 0.5
ml of each serum pool diluted 1:2 or 1:10, challenged approximately 18
h later with a lethal dose of either JEV strain SA14 (genotype III) or strain KE-093 (genotype I) and observed for 21 days. All mice in the non-immune serum groups developed clinical signs consistent with JEV infection or died, whereas high titer sera from both IXIARO and JE-VAX
® sera protected 90–100% of the animals. Statistical tests showed similar protection against both JEV strains SA14 and KE-093 and protection correlated with the anti-JEV antibody titer of IXIARO sera as measured by PRNT
50.
Ex vivo neutralizing antibody titers showed that almost all mice with a titer of 10 or greater were fully protected. In a separate study, analysis of geometric mean titers (GMTs) of the groups of mice vaccinated with different doses of IXIARO and challenged with JEV SA14 provided additional evidence that titers
≥
10 were protective.
Journal Article
Immunogenicity and safety of measles-rubella vaccine co-administered with attenuated Japanese encephalitis SA 14–14–2 vaccine in infants aged 8 months in China: a non-inferiority randomised controlled trial
by
Wannemuehler, Kathleen
,
Feng, Zijian
,
Wang, Huaqing
in
Adult
,
Allergies
,
Antibodies, Viral - blood
2019
In China, measles-rubella vaccine and live attenuated SA 14–14–2 Japanese encephalitis vaccine (LJEV) are recommended for simultaneous administration at 8 months of age, which is the youngest recommended age for these vaccines worldwide. We aimed to assess the effect of the co-administration of these vaccines at 8 months of age on the immunogenicity of measles-rubella vaccine.
We did a multicentre, open-label, non-inferiority, two-group randomised controlled trial in eight counties or districts in China. We recruited healthy infants aged 8 months who had received all scheduled vaccinations according to the national immunisation recommendations and who lived in the county of the study site. Enrolled infants were randomly assigned (1:1) to receive either measles-rubella vaccine and LJEV simultaneously (measles-rubella plus LJEV group) or measles-rubella vaccine alone (measles-rubella group). The primary outcome was the proportion of infants with IgG antibody seroconversion for measles 6 weeks after vaccination, and a secondary outcome was the proportion of infants with IgG antibody seroconversion for rubella 6 weeks after vaccination. Analyses included all infants who completed the study. We used a 5% margin to establish non-inferiority. This trial was registered at ClinicalTrials.gov (NCT02643433).
1173 infants were assessed for eligibility between Aug 13, 2015, and June 10, 2016. Of 1093 (93%) enrolled infants, 545 were randomly assigned to the measles-rubella plus LJEV group and 548 to the measles-rubella group. Of the infants assigned to each group, 507 in the measles-rubella plus LJEV group and 506 in the measles-rubella group completed the study. Before vaccination, six (1%) of 507 infants in the measles-rubella plus LJEV group and one (<1%) of 506 in the measles-rubella group were seropositive for measles; eight (2%) infants in the measles-rubella plus LJEV group and two (<1%) in the measles-rubella group were seropositive for rubella. 6 weeks after vaccination, measles seroconversion in the measles-rubella plus LJEV group (496 [98%] of 507) was non-inferior to that in the measles-rubella group (499 [99%] of 506; difference −0·8% [90% CI −2·6 to 1·1]) and rubella seroconversion in the measles-rubella plus LJEV group (478 [94%] of 507) was non-inferior to that in the measles-rubella group (473 [94%] of 506 infants; difference 0·8% [90% CI −1·8 to 3·4]). There were no serious adverse events in either group and no evidence of a difference between the two groups in the prevalence of any local adverse event (redness, rashes, and pain) or systemic adverse event (fever, allergy, respiratory infections, diarrhoea, and vomiting). Fever was the most common adverse event (97 [19%] of 507 infants in the measles-rubella plus LJEV group; 108 [21%] of 506 infants in the measles-rubella group).
The evidence of similar seroconversion and safety with co-administered LJEV and measles-rubella vaccines supports the co-administration of these vaccines to infants aged 8 months. These results will be important for measles and rubella elimination and the expansion of Japanese encephalitis vaccination in countries where it is endemic.
US Centers for Disease Control and Prevention, US Department of Health and Human Services; China–US Collaborative Program on Emerging and Re-emerging Infectious Diseases.
Journal Article
Making sense of Japanese : what the textbooks don't tell you
\"Making sense of Japanese is the fruit of one foolhardy American's thirty-year struggle to learn and teach the Language of the Infinite. Previously known as Gone fishin', this book has brought Jay Rubin more feedback than any of his literary translations or scholarly tomes, \"even if,\" he says, \"you discount the hate mail from spin-casters and the stray gill-netter.\" To convey his conviction that \"the Japanese language is not vague,\" Rubin has dared to explain how some of the most challenging Japanese grammatical forms work ...\" --Publisher description.
Japan Prepares for Total War
2013
The roots of Japan's aggressive, expansionist foreign policy
have often been traced to its concern over acute economic
vulnerability. Historian Michael Barnhart tests this assumption by
examining the events leading up to World War II in the context of
Japan's quest for economic security. Drawing on a wide array of
Japanese and American sources, this is the first English-language
book on the war's origins to be based on research in archives on
both sides of the Pacific.
Barnhart focuses on the critical years from 1938 to 1941 as he
investigates the development of Japan's drive for national economic
self-sufficiency and independence and the way in which this drive
shaped its internal and external policies. He also explores
American economic pressure on Tokyo and assesses its impact on
Japan's foreign policy and domestic economy. He concludes that
Japan's internal political dynamics, especially the bitter rivalry
between its army and navy, played a far greater role in propelling
the nation into war with the United States than did its economic
condition or even pressure from Washington.
Japan Prepares for Total War sheds new light on prewar Japan and
confirms the opinions of those in Washington who advocated economic
pressure against Japan. At a time of growing interest in
U.S.-Japanese economic relations, this book will be stimulating and
provocative reading for scholars and students of international
relations and American and Asian history.
The roots of Japan's aggressive, expansionist foreign policy
have often been traced to its concern over acute economic
vulnerability. Michael A. Barnhart tests this assumption by
examining the events leading up to World War II in the context of
Japan's quest for economic security, drawing on a wide array of
Japanese and American sources.Barnhart focuses on the critical
years from 1938 to 1941 as he investigates the development of
Japan's drive for national economic self-sufficiency and
independence and the way in which this drive shaped its internal
and external policies. He also explores American economic pressure
on Tokyo and assesses its impact on Japan's foreign policy and
domestic economy. He concludes that Japan's internal political
dynamics, especially the bitter rivalry between its army and navy,
played a far greater role in propelling the nation into war with
the United States than did its economic condition or even pressure
from Washington. Japan Prepares for Total War sheds new
light on prewar Japan and confirms the opinions of those in
Washington who advocated economic pressure against Japan.
Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of the Safety and Tolerability of IC51, an Inactivated Japanese Encephalitis Vaccine
2008
Background. Japanese encephalitis (JE) is the most important mosquito-borne viral encephalitis and has a high case fatality rate. It is caused by Japanese encephalitis virus. Improved vaccines are urgently needed for residents in countries of endemicity, travelers, and the military. The aim of the present trial was to evaluate the safety and tolerability of IC51, Intercell's Vero cell-derived, purified, inactivated JE vaccine. Methods. This was a randomized (3:1), double-blind, placebo-controlled, multicenter phase 3 trial. Healthy subjects were randomized to receive 2 doses of IC51 (n=2012) or placebo (n=663) at a 4-week interval. Adverse events following immunization (AEFI) were documented over a period of 2 months. Results. The rate of severe AEFI was similar in the IC51 group (0.5%) and the placebo group (0.9%). The rate of medically attended AEFI and all AEFI was also similar in the IC51 group and the placebo group. The same applied for all adverse events, including local and systemic tolerability. Importantly, there were no signs of acute allergic reactions. Conclusion. The Intercell JE vaccine IC51 had a safety profile similar to that of placebo. These data, together with the immunogenicity data from a recent phase 3 trial, form the basis of application for licensure of this vaccine. Trial registration. ClinicalTrials.gov identifier: NCT00605058.
Journal Article
A Japanese Encephalitis Vaccine From India Induces Durable and Cross-protective Immunity Against Temporally and Spatially Wide-ranging Global Field Strains
by
Singh, Anit
,
Gopinathan, K.
,
Rao, N. Bhuvaneswara
in
Adolescent
,
Adult
,
Antibodies, Neutralizing - blood
2015
Background. Japanese encephalitis (JE) is a vaccine-preventable acute disease. We report the results of a phase 2/3 trial of JENVAC, a Vero cell-derived vaccine developed using an Indian strain of JE virus (JEV). Methods. JENVAC was administered in 2 doses 28 days apart, and immunogenicity was compared to that from a single dose of SA-14-14-2, the only approved JE vaccine and regimen at the time in India. Results. After both the doses, seroconversion and seroprotection were >90% for JENVAC. For SA-14-14-2, seroconversion and seroprotection were 57.69% and 77.56%, respectively, on day 28 and 39.74% and 60.26%, respectively, on day 56. The geometric mean titers at day 28 and day 56 were 145.04 and 460.53, respectively, for JENVAC and 38.56 and 25.29, respectively, for SA-14-14-2. With a single dose of JENVAC, seroprotection titers lasted at least 12 months in >80% of the subjects. Following receipt of 2 doses, 61.17% of subjects retained seroprotection titers at 24 months, and immunogenicity criteria were higher than that for SA-14-14-2 at 12, 18, and 24 months each. Sera from JENVAC subjects neutralized JEV genotypes I, II, III, and IV equally well. Adverse events were not significantly different between the 2 vaccines. Conclusions. JENVAC elicits long-lasting, broadly protective immunity. Clinical Trials Registration. CTRI/2011/07/001855.
Journal Article