Japanese encephalitis virus 11072 Japanese encephalitis virus infects the lumen of the endoplasmic reticulum and rapidly accumulates substantial amounts of viral proteins. Japanese encephalitis Infection with JEV confers life-long immunity (Wiki: Japanese encephalitis). For JE, both arms have been considered to be important for protection from the disease, since passive transfer of neutralizing antibodies or virus-specific T cells including CTLs can protect mice from a lethal challenge (Konishi et al., 2003). Domestic pigs and wild birds are reservoirs of the virus; transmission to humans may cause severe symptoms. Japanese encephalitis virus is a virus from the family Flaviviridae. It causes the mosquito-borne Japanese encephalitis. Japanese encephalitis is the leading cause of viral encephalitis in Asia, with 30,000–50,000 cases reported annually. Case-fatality rates range from 0.3% to 60% and depends on the population and on age. Rare outbreaks in U.S. territories in Western Pacific have occurred. This disease often occurs in rural areas but not usually in urban areas. Severe rigors, fever, headache and malaise are non-specific symptoms for the first week. Signs which develop during the acute encephalitic stage include neck rigidity, cachexia, hemiparesis, convulsions, and fever. Mental retardation developed from this disease usually leads to coma. Mortality of this disease varies but is generally much higher in children (Wiki: Japanese encephalitis). Baboon Papio cynocephalus 9556 Bank vole Clethrionomys glareolus 447135 Bear Ursus americanus 9643 Birds Passeroidea 175121 Brown Trout Salmo trutta 8032 Buffalo Bison bison 9901 Carnivores Vulpes 9625 Cat Felis catus 9685 Catfishes Siluriformes 7995 Cattle Bos taurus 9913 Chicken Gallus gallus 9031 Chimpanzee Pan troglodytes 9598 chinchillas Chinchillidae 10150 Copper Pheasant Syrmaticus soemmerringii 9067 Deer Cervus elaphus 9860 Deer mouse Peromyscus maniculatus 10042 Dog Canis familiaris 9615 Ducks Anas 8835 Ferret Mustela putorius furo 9669 Fish Hyperotreti 117565 Gerbil Gerbillina 10045 Goat Capra hircus 9925 Gray wolf Canis lupus 9612 Guinea pig Cavia porcellus 10141 Hamster Mesocricetus auratus 10036 Horse Equus caballus 9796 Human Homo sapiens 9606 Macaque Macaca fascicularis 9541 Mongolian Gerbil Meriones unguiculatus 10047 Monkey Platyrrhini 9479 Mouse Mus musculus 10090 None None Parrot Psittacidae 9224 Pig Sus scrofa 9823 Rabbit Oryctolagus cuniculus 9986 Rainbow trout Oncorhynchus mykiss 8022 Rat Rattus 10114 Raven Corvus corax 56781 sei whale Balaenoptera borealis 9768 Sheep Ovis aries 9940 Squirrel Spermophilus richardsonii 37591 Tree shrew Tupaiidae 9393 Trouts, salmons & chars Salmoninae 504568 Turkey Meleagris gallopavo 9103 Vole Microtus ochrogaster 79684 Water buffalo Bubalus bubalis 391902 ALVAC-JEV VO_0004777 Recombinant vector vaccine Research Intramuscular injection (i.m.) Poxvirus-vectored vaccines for Japanese encephalitis (JE), NYVAC-JEV and ALVAC-JEV(Raengsakulrach et al., 1999). Intramuscular injection (i.m.) The vaccines were given to four monkeys each on study days 0 and 28 along with saline placebo on day 7. For controls, the licensed BIKEN JE vaccine and a saline placebo were given to other groups of four monkeys on days 0, 7, and 28 (Raengsakulrach et al., 1999). VO_0003057 This study suggests that the NYVAC-JEV and ALVAC-JEV vaccines are safe and immunogenic in monkeys and that the NYVAC-JEV and BIKEN vaccines are effective in protecting monkeys from encephalitis (Raengsakulrach et al., 1999). Two months after the booster dose, all 16 monkeys were challenged intranasally with one 90% effective dose of JEV strain KE-93 (AP61-1, C6/36-1, Mm-1, SM-2) (Raengsakulrach et al., 1999). Ixiaro Japanese Encephalitis Vaccine, Inactivated, Adsorbed IXIARO Valneva SE VO_0011558 Inactivated or "killed" vaccine Licensed Intramuscular injection (i.m.) USA, Canada Aluminum hydroxide Store in a refrigerator at 2° to 8° C (35° to 46° F). Do not freeze. JEV strain SA14-14-2 is propagated in Vero cells, and harvested. The harvested virus suspension is treated with protamine sulfate to remove contaminating DNA and proteins and centrifuged. Virus is inactivated by formaldehyde and aluminum hydroxide is added Ref917:FDA: Ixiaro]. Intramuscular injection (i.m.) Japanese encephalitis virus (JEV) Recombinant vector vaccine Licensed Intramuscular injection (i.m.) Intramuscular injection (i.m.) Japanese encephalitis virus DNA vaccine encoding E protein VO_0011353 DNA vaccine Research Expression vectors pcDL-SRα296 and pCAGGS Intravenous injection (i.v.) Intravenous injection (i.v.) Japanese encephalitis virus PrM and E protein DNA vaccine construction Plasmid pSLKJ12 contains the premembrane signal sequence as well as the premembrane (PrM) and envelope (E) genes of the Sagayama strain of JEV. The viral sequence, spanning nucleotides 408 to 2477, was retrieved from this plasmid by PstI-EcoRI digestion. The fragment was cloned into the eukaryotic expression vectors pcDL-SRα296 and pCAGGS, generously provided by Y. Takebe (Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan) and J. Miyazaki (Division of Stem Cell Regulation Research, G6, Osaka University Medical School, Suita, Osaka, Japan), respectively. They are purified and designated pSRαJ12 and pCAGJ12, respectively (Zhao et al., 2003). DNA vaccine construction Plasmid pSLKJ12 contains the premembrane signal sequence as well as the premembrane (PrM) and envelope (E) genes of the Sagayama strain of JEV. The viral sequence, spanning nucleotides 408 to 2477, was retrieved from this plasmid by PstI-EcoRI digestion. The fragment was cloned into the eukaryotic expression vectors pcDL-SRα296 and pCAGGS, generously provided by Y. Takebe (Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan) and J. Miyazaki (Division of Stem Cell Regulation Research, G6, Osaka University Medical School, Suita, Osaka, Japan), respectively (Zhao et al., 2003). BALB/c For the protection test, 3-week-old female BALB/c mice were inoculated with either 50, 5, or 0.5 μg of the mixture on days 0 and 9 intravenously or intradermally (Zhao et al., 2003). Researchers established a simple and effective method for DNA immunization against Japanese encephalitis virus (JEV) infection with plasmids encoding the viral PrM and E proteins and colloidal gold. After being inoculated twice, BALB/c mice were found to resist challenge with 100,000 times the 50% lethal dose (LD(50)) of JEV (Beijing-1 strain) even when immunized with a relatively small dose of 0.5 micro g of plasmid DNA (Zhao et al., 2003). On day 22, all immunized mice were challenged by an intraperitoneal injection of 100,000 times the LD50 of JEV (Beijing-1 strain, 0.15 ml), at which time they were simultaneously inoculated intracerebrally with 25 μl of saline into the right hemisphere of their brains with a 27-gauge one-stop needle (Top Injection Needle, Tokyo, Japan) (Zhao et al., 2003). Japanese encephalitis virus DNA vaccine encoding NS1 (pUSK-NS1) VO_0011500 DNA vaccine Research pUSK Intramuscular injection (i.m.) Intramuscular injection (i.m.) Japanese encephalitis virus NS1 DNA vaccine construction NS1 gene of Japanese encephalitis virus (JEV) SA14-14-2 strain was produced by reverse transcriptase-mediated PCR (RT-PCR) and was cloned into vector pUSK to form recombinant plasmid (designed as pUSK-NS1) (Xu et al., 2004). BALB/c Ten 6-week-old Balb/c mice and eight 2-days old piglets were immunized with 5.0 log10pfu of the TK−/gG−/NS1+ mutant, while another equal number of animal in control groups with PBS (Xu et al., 2004). Balb/c mice and swine vaccinated with TK(-)/gG(-)/NS1(+) expressing NS1 protein of JEV could confer protective immunity against lethal challenge of the virulent PRV Ea strain and develop a good humoral and cellular immune response against JEV (Xu et al., 2004). The challenge was performed with PRV Ea strain at a concentration of 6.5 log10pfu (LD50=10−4.5) at day 7 for mice and day 14 for piglets post-vaccination (Xu et al., 2004). Japanese encephalitis virus DNA vaccine encoding PrM VO_0011345 DNA vaccine Research Expression vectors pcDL-SRα296 and pCAGGS Intravenous injection (i.v.) Intravenous injection (i.v.) envelope protein DNA vaccine construction Plasmid pSLKJ12 contains the premembrane signal sequence as well as the premembrane (PrM) and envelope (E) genes of the Sagayama strain of JEV. The viral sequence, spanning nucleotides 408 to 2477, was retrieved from this plasmid by PstI-EcoRI digestion. The fragment was cloned into the eukaryotic expression vectors pcDL-SRα296 and pCAGGS, generously provided by Y. Takebe (Laboratory of Molecular Virology and Epidemiology, AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan) and J. Miyazaki (Division of Stem Cell Regulation Research, G6, Osaka University Medical School, Suita, Osaka, Japan), respectively. They are purified and designated pSRαJ12 and pCAGJ12, respectively (Zhao et al., 2003). BALB/c For the protection test, 3-week-old female BALB/c mice were inoculated with either 50, 5, or 0.5 μg of the mixture on days 0 and 9 intravenously or intradermally (Zhao et al., 2003). Researchers established a simple and effective method for DNA immunization against Japanese encephalitis virus (JEV) infection with plasmids encoding the viral PrM and E proteins and colloidal gold. After being inoculated twice, BALB/c mice were found to resist challenge with 100,000 times the 50% lethal dose (LD(50)) of JEV (Beijing-1 strain) even when immunized with a relatively small dose of 0.5 micro g of plasmid DNA (Zhao et al., 2003). On day 22, all immunized mice were challenged by an intraperitoneal injection of 100,000 times the LD50 of JEV (Beijing-1 strain, 0.15 ml), at which time they were simultaneously inoculated intracerebrally with 25 μl of saline into the right hemisphere of their brains with a 27-gauge one-stop needle (Top Injection Needle, Tokyo, Japan) (Zhao et al., 2003). Japanese encephalitis virus DNA Vaccine P-JEV VO_0004586 DNA vaccine Research pcDNA3.1/V5-His-P-JEV [Ref2719:Kulkarni et al., 2012] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction DNA vaccine construction Anti-JEV antibodies were detectable in all mouse groups 31 days after immunization. Levels of these antibodies increased after the first booster immunization and were further enhanced after the second booster dose. Following the challenge, pcDNA3.1/V5-His-P-JEV immunized mice showed significantly enhanced JEV antibody titres (Kulkarni et al., 2012). Control mice received 1 μg of pcDNA3.1/V5-His plasmid per dose. While same amount of recombinant plasmid, pcDNA3.1/V5-His-P-JEV was used to immunize the experimental group. Groups of BALB/c mice (n = 10), received two booster doses with equal amount of DNA after every 2 weeks (Kulkarni et al., 2012). VO_0003057 Approximately 83% of mice immunized with the vaccine survived the challenge injection (Kulkarni et al., 2012). At 6 weeks after immunization, mice were challenged with lethal dose of 100LD50 with JEV 733913 strain by intraperitonial route, followed by 1% starch by the intracerebral route to breach the blood brain barrier (Kulkarni et al., 2012). Japanese encephalitis virus DNA Vaccine pCJ-3/E encoding E VO_0004587 DNA vaccine Research pCJ-3/E [Ref2720:Wu et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction The vaccine enhanced the production of higher titers of neutralizing antibodies, and generated both cellular and humoral immunity (Wu et al., 2006). All mice were immunized intramuscularly at 6 to 8 weeks of age. Groups of five mice were anesthetized and injected three times at 3-week intervals with 100 μg of DNA (Wu et al., 2006). VO_0003057 In terms of survival rates of immunized mice challenged with JEV virus at week 16, 100% protection was seen with pCJ-3/E-immunized mice (Wu et al., 2006). For a lethal challenge experiment, C3H/HeN mice were injected intraperitoneally with 50 times the LD50 of JEV Beijing-1 and intracerebrally with PBS (Wu et al., 2006). Japanese encephalitis virus DNA vaccine pUJENS3 VO_0011501 DNA vaccine Research pUBIQ vector Intramuscular injection (i.m.) Intramuscular injection (i.m.) Japanese encephalitis virus non-structural protein NS3 DNA vaccine construction Amplified DNA fragments containing the NS3 gene was ligated to the pUBIQ vector at the EcoRI/XbaI site to construct pUJENS3 (Konishi et al., 2003). BALB/c Four-to-six-week-old male BALB/c mice were immunized intramuscularly (i.m.) with 100 μg of plasmid DNA one to three times at intervals of 2 weeks. For evaluation of CTL induction, spleens were collected from groups of two immunized mice 2–4 weeks after the last immunization (Konishi et al., 2003). Researchers constructed plasmid DNAs encoding JE virus proteins. Cytotoxic T lymphocytes (CTLs) were induced by NS3 in a mouse model. Three immunizations with pUJENS3 provided a 50% partial protection from a lethal dose of JE virus (Konishi et al., 2003). For evaluation of protective efficacy, groups of 6–12 immunized mice were bled retroorbitally for evaluating pre-challenge serum neutralizing antibody titers, and then challenged i.p. with 100 or 400 LD50 of the P3 strain of JE virus, 6 weeks after the first immunization. Mice were observed for 21 days, and surviving mice were bled for evaluating post-challenge serum neutralizing antibody titers. For monitoring virus load following challenge, groups of 18 immunized mice were challenged with 100 LD50 of the P3 strain, and 600–700 μl of blood and the whole brain were collected 1 h (day 0) or consecutive 5 days (days 1–5) following challenge from 3 mice per day per group (Konishi et al., 2003). Japanese encephalitis virus DNA vaccine pUJENS5 VO_0011352 DNA vaccine Research pUBIQ vector Intramuscular injection (i.m.) Intramuscular injection (i.m.) Japanese encephalitis virus NS5 DNA vaccine construction Amplified DNA fragments containing the NS5 gene was ligated to the pUBIQ8 vector at the BspEI and/or XbaI sites to construct pUJENS5 (Konishi et al., 2003). BALB/c Four-to-six-week-old male BALB/c mice were immunized intramuscularly (i.m.) with 100 μg of plasmid DNA one to three times at intervals of 2 weeks. For evaluation of CTL induction, spleens were collected from groups of two immunized mice 2–4 weeks after the last immunization (Konishi et al., 2003). Researchers constructed plasmid DNAs encoding JE virus proteins. Cytotoxic T lymphocytes (CTLs) were induced by NS5 in a mouse model. Three immunizations with pUJENS5 provided a 57% partial protection from a lethal dose of JE virus (Konishi et al., 2003). For evaluation of protective efficacy, groups of 6–12 immunized mice were bled retroorbitally for evaluating pre-challenge serum neutralizing antibody titers, and then challenged i.p. with 100 or 400 LD50 of the P3 strain of JE virus, 6 weeks after the first immunization. Mice were observed for 21 days, and surviving mice were bled for evaluating post-challenge serum neutralizing antibody titers. For monitoring virus load following challenge, groups of 18 immunized mice were challenged with 100 LD50 of the P3 strain, and 600–700 μl of blood and the whole brain were collected 1 h (day 0) or consecutive 5 days (days 1–5) following challenge from 3 mice per day per group (Konishi et al., 2003). Japanese encephalitis virus vaccine BV-G-E VO_0011516 Recombinant vector vaccine Research baculovirus pseudotyped with vesicular stomatitis virus glycoprotein (VSVG) Intramuscular injection (i.m.) Intramuscular injection (i.m.) Japanese encephalitis virus envelope protein Recombinant vector construction Recombinant pseudotype baculovirus (BV-G-E) was generated by inserting JEV E gene fragment into pFastBac-VSV/G vector. BALB/c mice were immunized with BV-G-E and challenged with JEV wild-type strain. The neutralization antibody, interferon (IFN)- expression and release, and survival rate were analysed and compared with the group of immunized with inactivated vaccine and DNA vaccine (pc-E) encoding the same gene of JEV (Li et al., 2009). BALB/c Four-week old female BALB/c mice (purchased from the Animal Centre, Institute of Medicine (Hubei Province, China) were randomly divided into seven groups (15 mice per group). Three groups were injected intramuscularly (i.m.) with 100 µl of PBS containing 1 × 10^8, 1 × 10^9 and 1 × 10^10 PFU of BV-G-E, respectively. The other three groups were injected intramuscularly with 100 µl of PBS containing 1 × 10^10 PFU of BV-G-EGFP or 100 µg of pc-E (a DNA vaccine construct expressing E protein) or 100 µl inactivated vaccine. The last group was used as a negative control by intramuscularly injecting 100 µl of PBS. Booster immunizations were identically performed 3 weeks later (Li et al., 2009). Researchers constructed a recombinant pseudotype baculovirus encoding the JEV envelope (E) protein and demonstrated that it could elicit high protective immunity in mice. Intramuscular injections of BV-G-E at various doses into mice produced higher levels of JEV-specific neutralizing antibodies, IFN-gamma and better protective efficacy against a lethal challenge with JEV than that of pc-E. Furthermore, BV-G-E could elicit a higher level of cellular immunity response and provide equal protective efficacy against JEV challenge compared to inactivated vaccine (Li et al., 2009). A subset of immunized mice was intraperitoneally (i.p.) challenged with 105 PFU of wild-type JEV P3 in 0.1 ml at 6 weeks following the initial immunization. Mouse mortality was monitored daily for 3 weeks (Li et al., 2009). An evident dose-dependent pattern of IFN-gamma production could be observed in mice immunized with BV-G-E. As expected, no significant production of IFN-γ was detected in PBS-inoculated mice. Interestingly, the mean relative IFN-γ mRNA expression in the group of BV-G-EGFP was also significantly higher than that of pc-E vaccinated mice in splenocytes (Li et al., 2009). licensed Japanese encephalitis human vaccine Generic Unknown VO_0000665 Inactivated or "killed" vaccine Licensed A generic representation of vaccines utilized to prevent Japanese encephalitis infection in humans, most commonly based on inactivated (killed) virus preparations. These vaccines are historically the most prevalent licensed type for human use against Japanese encephalitis. NYVAC-JEV VO_0004776 Recombinant vector vaccine Research Intramuscular injection (i.m.) Poxvirus-vectored vaccines for Japanese encephalitis (JE), NYVAC-JEV and ALVAC-JEV(Raengsakulrach et al., 1999). Intramuscular injection (i.m.) The vaccines were given to four monkeys each on study days 0 and 28 along with saline placebo on day 7. For controls, the licensed BIKEN JE vaccine and a saline placebo were given to other groups of four monkeys on days 0, 7, and 28 (Raengsakulrach et al., 1999). VO_0003057 This study suggests that the NYVAC-JEV and ALVAC-JEV vaccines are safe and immunogenic in monkeys and that the NYVAC-JEV and BIKEN vaccines are effective in protecting monkeys from encephalitis (Raengsakulrach et al., 1999). Two months after the booster dose, all 16 monkeys were challenged intranasally with one 90% effective dose of JEV strain KE-93 (AP61-1, C6/36-1, Mm-1, SM-2) (Raengsakulrach et al., 1999). NYVAC-JEV- prM/E/ NS1 VO_0004780 Recombinant vector vaccine Research Intramuscular injection (i.m.) Highly attenuated strain of vaccinia virus (NYVAC) was engineered to express the Japanese encephalitis virus (JEV) prM, E, and NS1 genes or the prM and E genes (Konishi et al., 1992). Intramuscular injection (i.m.) Recombinant vector construction A highly attenuated strain of vaccinia virus (NYVAC) was engineered to express the Japanese encephalitis virus (JEV) prM, E, and NS1 genes or the prM and E genes (Konishi et al., 1992). Recombinant vector construction A highly attenuated strain of vaccinia virus (NYVAC) was engineered to express the Japanese encephalitis virus (JEV) prM, E, and NS1 genes or the prM and E genes (Konishi et al., 1992). Recombinant protein preparation A highly attenuated strain of vaccinia virus (NYVAC) was engineered to express the Japanese encephalitis virus (JEV) prM, E, and NS1 genes or the prM and E genes (Konishi et al., 1992). The recombinant viruses were tested as vaccine candidates in pigs, a natural host of JEV. JEV-neutralizing and hemagglutination-inhibiting antibodies appeared in swine sera 7 days after immunization with 108 PFU of the recombinant viruses and increased after a second dose at 28 days (Konishi et al., 1992). VO_0003057 The JEV levels detected in the serum after JEV challenge were significantly reduced in animals inoculated with the recombinant viruses (Konishi et al., 1992). JEV challenge (d56) of the swine with 2 × 10^8 PFU of JEV (Konishi et al., 1992). E Japanese encephalitis virus VO_0011145 16445023 CDD:279241 CDD:213392 CDD:213897 11072 ? envelope protein 7.88 49812.26 577 Flavivirus glycoprotein, central and dimerization domains; pfam00869 >AAK31640.1 envelope protein, partial [Japanese encephalitis virus] FNCLGMGNRDFIEGASGATWVDLVLEGDSCLTIMANDKPTLDVRMINIEASQLAEVRSYCYHASVTDIST VARCPTTGEAHNEKRADSSYVCKQGFTDRGWGNGCGLFGKGSIDTCAKFSCTSKAIGRTIQPENIKYKVG IFVHGATTSENHGNYSAQVGASQAAKFTVTPNAPSITLKLGDYGEVTLDCEPRSGLNTEAFYVMTVGSKS FLVHREWFHDLALPWTSPSSTAWRNRELLMEFEEAHATKQSVVALGSQEGGLHQALAGAIVVEYSSSVKL TSGHLKCRLKMDKLALKGTTYGMCTEKFSFAKNPADTGHGTVVIELSYSGSDGPCKIPIVSVASLNDMTP VGRLVTVNPFVATSSANSKVLVEMEPPFGDSYIVVGRGDKQINHHWHKAGSTLGKAFSTTLKGAQRLAAL GDTAWDFGSIGGVFNSIGKAVHQVFGGAFRTLFGGMSWITQGLMGALLLWMGVNARDRSIALAFLATGGV LVFLATNVHA Protective antigen Researchers constructed a recombinant pseudotype baculovirus encoding the JEV envelope (E) protein and demonstrated that it could elicit high protective immunity in mice. Intramuscular injections of BV-G-E at various doses into mice produced higher levels of JEV-specific neutralizing antibodies, IFN-gamma and better protective efficacy against a lethal challenge with JEV than that of pc-E. Furthermore, BV-G-E could elicit a higher level of cellular immunity response and provide equal protective efficacy against JEV challenge compared to inactivated vaccine [Ref1157:Li et al., 2009]. Ifng (Interferon gamma) Mouse 15978 33468859 NM_008337 NP_032363.1 MGI:107656; UniProt:P01580 10090 ? >gi|145966741|ref|NM_008337.3| Mus musculus interferon gamma (Ifng), mRNA ATAGCTGCCATCGGCTGACCTAGAGAAGACACATCAGCTGATCCTTTGGACCCTCTGACTTGAGACAGAA GTTCTGGGCTTCTCCTCCTGCGGCCTAGCTCTGAGACAATGAACGCTACACACTGCATCTTGGCTTTGCA GCTCTTCCTCATGGCTGTTTCTGGCTGTTACTGCCACGGCACAGTCATTGAAAGCCTAGAAAGTCTGAAT AACTATTTTAACTCAAGTGGCATAGATGTGGAAGAAAAGAGTCTCTTCTTGGATATCTGGAGGAACTGGC AAAAGGATGGTGACATGAAAATCCTGCAGAGCCAGATTATCTCTTTCTACCTCAGACTCTTTGAAGTCTT GAAAGACAATCAGGCCATCAGCAACAACATAAGCGTCATTGAATCACACCTGATTACTACCTTCTTCAGC AACAGCAAGGCGAAAAAGGATGCATTCATGAGTATTGCCAAGTTTGAGGTCAACAACCCACAGGTCCAGC GCCAAGCATTCAATGAGCTCATCCGAGTGGTCCACCAGCTGTTGCCGGAATCCAGCCTCAGGAAGCGGAA AAGGAGTCGCTGCTGATTCGGGGTGGGGAAGAGATTGTCCCAATAAGAATAATTCTGCCAGCACTATTTG AATTTTTAAATCTAAACCTATTTATTAATATTTAAAACTATTTATATGGAGAATCTATTTTAGATGCATC AACCAAAGAAGTATTTATAGTAACAACTTATATGTGATAAGAGTGAATTCCTATTAATATATGTGTTATT TATAATTTCTGTCTCCTCAACTATTTCTCTTTGACCAATTAATTATTCTTTCTGACTAATTAGCCAAGAC TGTGATTGCGGGGTTGTATCTGGGGGTGGGGGACAGCCAAGCGGCTGACTGAACTCAGATTGTAGCTTGT ACCTTTACTTCACTGACCAATAAGAAACATTCAGAGCTGCAGTGACCCCGGGAGGTGCTGCTGATGGGAG GAGATGTCTACACTCCGGGCCAGCGCTTTAACAGCAGGCCAGACAGCACTCGAATGTGTCAGGTAGTAAC AGGCTGTCCCTGAAAGAAAGCAGTGTCTCAAGAGACTTGACACCTGGTGCTTCCCTATACAGCTGAAAAC TGTGACTACACCCGAATGACAAATAACTCGCTCATTTATAGTTTATCACTGTCTAATTGCATATGAATAA AGTATACCTTTGCAACC >gi|33468859|ref|NP_032363.1| interferon gamma [Mus musculus] MNATHCILALQLFLMAVSGCYCHGTVIESLESLNNYFNSSGIDVEEKSLFLDIWRNWQKDGDMKILQSQI ISFYLRLFEVLKDNQAISNNISVIESHLITTFFSNSKAKKDAFMSIAKFEVNNPQVQRQAFNELIRVVHQ LLPESSLRKRKRSRC IFN-gamma plays a critical role in Th1 type immune response. It is important for protection against infections by various viruses and intracellular bacteria. Vaximmutor The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced strong TB Ag-specific IFN-gamma immune responses in splenocytes [Ref2101:Wang et al., 2009]. M protein Japanese encephalitis virus strain TS3306 4572323 CDD:279856 11072 ? M protein 5.84 10361.74 156 isolated from the Torres Strait >AAD23744.1 M protein, partial [Japanese encephalitis virus] MKLSNFQGKLLMTVNNTDIADVIVIPTSKGENRCWVRAIDVGYMCEDTITYECPKLTTGNDPEDVDCWCD NQEVYIQYGRCTRTRHSKRSRR Protective antigen NS1 Japanese encephalitis virus VO_0011147 18418672 CDD:279316 11072 ? NS1 protein 8.12 16884.93 218 isolated from porcine sera >AAL68990.1 NS1 protein, partial [Japanese encephalitis virus] ELIIPHTIAGPRSKHNRREGYKTQNQGPWDENGIVLDFDYCPGTKVTITEDCGKRGPSIRTTTDSGKLIT DWCCRSCSLPPLRFRTENGCWYGMEIRPVRHDETTLVRSQVDAFNGEMIDPFQLGLLVMFLATQEVLRKR WTARLTIPAVL Protective antigen Balb/c mice and swine vaccinated with TK(-)/gG(-)/NS1(+) expressing NS1 protein of JEV could confer protective immunity against lethal challenge of the virulent PRV Ea strain and develop a good humoral and cellular immune response against JEV [Ref1159:Xu et al., 2004]. NS3 Japanese encephalitis virus VO_0011148 27696332 CDD:279317 CDD:214692 CDD:284962 CDD:238005 CDD:304359 CDD:238034 11072 ? non-structural protein NS3 7.14 64684.98 699 proteinase and putative helicase >NP_775670.1 non-structural protein NS3 [Japanese encephalitis virus] GGVFWDTPSPKPCSKGDTTTGVYRIMARGILGTYQAGVGVMYENVFHTLWHTTRGAAIMSGEGKLTPYWG SVKEDRIAYGGPWRFDRKWNGTDDVQVIVVEPGKAAVNIQTKPGVFRTPFGEVGAVSLDYPRGTSGSPIL DSNGDIIGLYGNGVELGDGSYVSAIVQGDRQEEPVPEAYTPNMLRKRQMTVLDLHPGSGKTRKILPQIIK DAIQQRLRTAVLAPTRVVAAEMAEALRGLPVRYQTSAVQREHQGNEIVDVMCHATLTHRLMSPNRVPNYN LFVMDEAHFTDPASIAARGYIATKVELGEAAAIFMTATPPGTTDPFPDSNAPIHDLQDEIPDRAWSSGYE WITEYAGKTVWFVASVKMGNEIAMCLQRAGKKVIQLNRKSYDTEYPKCKNGDWDFVITTDISEMGANFGA SRVIDCRKSVKPTILEEGEGRVILGNPSPITSASAAQRRGRVGRNPNQVGDEYHYGGATSEDDSNLAHWT EAKIMLDNIHMPNGLVAQLYGPEREKAFTMDGEYRLRGEEKKNFLELLRTADLPVWLAYKVASNGIQYTD RRWCFDGPRTNAILEDNTEVEIVTRMGERKILKPRWLDARVYADHQALKWFKDFAAGKR Protective antigen Researchers constructed plasmid DNAs encoding JE virus proteins. Cytotoxic T lymphocytes (CTLs) were induced by NS3 in a mouse model. Three immunizations with pUJENS3 provided a 50% partial protection from a lethal dose of JE virus [Ref1160:Konishi et al., 2003]. NS5 Japanese encephalitis virus VO_0011149 158702649 CDD:279336 11072 ? NS5 9.89 8854.45 135 Flavivirus RNA-directed RNA polymerase; pfam00972 >ABW77689.1 NS5, partial [Japanese encephalitis virus] KREKKPGEFGKAKGSRAIWFMWLGARYLEFEALGFLNEDHWLSRENSGGGVEGSGVQKLGYILRDIAGKQ GGKMYAD Protective antigen Researchers constructed plasmid DNAs encoding JE virus proteins. Cytotoxic T lymphocytes (CTLs) were induced by NS5 in a mouse model. Three immunizations with pUJENS5 provided a 57% partial protection from a lethal dose of JE virus [Ref1160:Konishi et al., 2003]. PrM Japanese encephalitis virus VO_0011146 90019439 CDD:279856 11072 ? PrM 4.01 8654.05 138 Flavivirus polyprotein propeptide; pfam01570 >ABD84370.1 PrM, partial [Japanese encephalitis virus] VIACVGAMKLSNFQGKLLMTINKTDIADVIVIPTSKGENRCWVRAIDVGYMCEDTITYECPKLTMGNDPE DVDCWCDNQE Protective antigen Researchers established a simple and effective method for DNA immunization against Japanese encephalitis virus (JEV) infection with plasmids encoding the viral PrM and E proteins and colloidal gold. After being inoculated twice, BALB/c mice were found to resist challenge with 100,000 times the 50% lethal dose (LD(50)) of JEV (Beijing-1 strain) even when immunized with a relatively small dose of 0.5 micro g of plasmid DNA [Ref1158:Zhao et al., 2003]. FDA: Ixiaro website http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm179132.htm FDA: JE-Vax website http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/ucm094048.htm Hua et al., 2014 journal Hua RH, Liu LK, Huo H, Li YN, Guo LP, Wang XL, Qin CF, Bu ZG 2014 185 103-109 Virus research Konishi et al., 1992 journal Konishi E, Pincus S, Paoletti E, Laegreid WW, Shope RE, Mason PW 1992 190 1 454-458 Virology Konishi et al., 2003 journal Konishi E, Ajiro N, Nukuzuma C, Mason PW, Kurane I 2003 21 25-26 3675-3683 Vaccine Kulkarni et al., 2012 journal Kulkarni R, Sapkal G, Gore M 2012 170 1-2 118-125 Virus research Li et al., 2009 journal Li Y, Ye J, Cao S, Xiao S, Zhao Q, Liu X, Jin M, Chen H 2009 11 1 57-65 The journal of gene medicine Qian et al., 2015 journal Qian P, Zhi X, Wang B, Zhang H, Chen H, Li X 2015 12 214 Virology journal Raengsakulrach et al., 1999 journal Raengsakulrach B, Nisalak A, Gettayacamin M, Thirawuth V, Young GD, Myint KS, Ferguson LM, Hoke CH Jr, Innis BL, Vaughn DW 1999 60 3 343-349 The American journal of tropical medicine and hygiene Sheets et al., 2006 journal Sheets RL, Stein J, Manetz TS, Duffy C, Nason M, Andrews C, Kong WP, Nabel GJ, Gomez PL 2006 91 2 610-619 Toxicological sciences : an official journal of the Society of Toxicology Wiki: Japanese encephalitis website http://en.wikipedia.org/wiki/Japanese_encephalitis Wu et al., 2006 journal Wu CJ, Li TL, Huang HW, Tao MH, Chan YL 2006 8 11 2578-2586 Microbes and infection / Institut Pasteur Xu et al., 2004 journal Xu G, Xu X, Li Z, He Q, Wu B, Sun S, Chen H 2004 22 15-16 1846-1853 Vaccine Yasuda et al., 1990 journal Yasuda A, Kimura-Kuroda J, Ogimoto M, Miyamoto M, Sata T, Sato T, Takamura C, Kurata T, Kojima A, Yasui K 1990 64 6 2788-2795 Journal of virology Zhao et al., 2003 journal Zhao Z, Wakita T, Yasui K 2003 77 7 4248-4260 Journal of virology