Dengue Virus 12637 During the feeding of mosquitoes on humans, DENV is presumably injected into the bloodstream, with spillover in the epidermis and dermis, resulting in infection of immature Langerhans cells (epidermal dendritic cells [DC]), and keratinocytes. Infected cells then migrate from site of infection to lymph nodes, where monocytes and macrophages are recruited, which become targets of infection. Consequently, infection is amplified and virus is disseminated through the lymphatic system. As a result of this primary viremia, several cells of the mononuclear lineage, including blood-derived monocytes, myeloid DC, and splenic and liver macrophages are infected (Martina et al., 2009). Dengue Fever In most acute virus infection models, the presence of antibodies, both neutralizing and nonneutralizing, correlates with control, elimination, and eventually protection (Martina et al., 2009). Dengue is transmitted to humans by Aedes mosquitoes, mainly Aedes aegypti. There is no animal model of disease that mimics the disease in humans (Martina et al., 2009). Dengue (DEN) viruses belong to the family Flaviviridae and consist of four distinct antigenic serotypes, DEN1–4. DEN viruses are transmitted primarily by the mosquito Aedes aegypti and cause over 100 million human infections per year, which are manifested clinically by either DEN fever (DF), a self-limited febrile illness, or more severe DEN hemorrhagic fever/DEN shock syndrome (DHF/DSS) usually with a mortality that ranges from 1 to 5%. Epidemic DF/DHF has been emerging as one of the most important global public health problems in the tropical and subtropical countries at the beginning of the 21st century. It is imperative to support research on the development of new mosquito control technology and on the establishment of preventive strategies, including the development of effective and safe dengue vaccines (Liu et al., 2006). 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 CAdVax-Den12/Den34 VO_0004643 Recombinant vector vaccine Research Intramuscular injection (i.m.) using a complex adenovirus vector, by incorporating the genes expressing premembrane (prM) and envelope (E) proteins of dengue virus types 1 and 2 (dengue-1 and -2, respectively) (CAdVax-Den12) or dengue-3 and -4 (CAdVax-Den34) (Raviprakash et al., 2008). Intramuscular injection (i.m.) Rhesus macaques were vaccinated by intramuscular inoculation of a tetravalent dengue vaccine formulated by combining the two bivalent vaccine constructs (Raviprakash et al., 2008). VO_0003057 For both of these virus challenge studies, significant protection from viremia was demonstrated for all four dengue virus serotypes in vaccinated animals. Viremia from dengue-1 and dengue-3 challenges was completely blocked, whereas viremia from dengue-2 and dengue-4 was significantly reduced, as well as delayed, compared to that of control-vaccinated animals (Raviprakash et al., 2008). The ability of the vaccine to induce rapid, as well as sustained, protective immune responses was examined with two separate live-virus challenges administered at 4 and 24 weeks after the final vaccination (Raviprakash et al., 2008). Dengue DNA Vaccine encoding NS1 Protein VO_0011454 DNA vaccine Research pcDNA3 [Ref1374:Wu et al., 2003] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction C57/BL6, Balb/c, and C3H Groups of 3–4 weeks old female C3H mice were initially immunized with 80 μg of recombinant DNA pD2NS1, or pcDNA3 as a control. Recombinant pD2NS1 in PBS, control pcDNA3 in PBS, or PBS buffer alone was intramuscularly (i.m.) injected into the mouse thighs; the mice were subsequently boosted twice using the same method at 1 week interval (Wu et al., 2003). Intravenously challenged by lethal DEN-2, mice vaccinated with NS1-DNA exhibited a delay onset of paralysis, a marked decrease of morbidity, and a significant enhancement of survival (Wu et al., 2003). One week after the final boost, mice were i.v. challenged with 5×10^6 plaque-forming units of PL046 in 100 μl PBS. The mice after virus challenge were monitored daily for morbidity and mortality for weeks (Wu et al., 2003). Dengue Subunit E Protein Vaccine VO_0011457 Subunit vaccine Research Baculovirus [Ref1371:Delenda et al., 1994] Intraperitoneal injection (i.p.) Intraperitoneal injection (i.p.) Recombinant protein preparation Baculovirus was used to generate the recombinant protein (Delenda et al., 1994). BALB/c Three-week-old female BALB/c mice were immunized by intraperitoneal injection on days 1,7, 21 and 56 with 200 gl of baculovirus infected Sf9 cell lysates (CL) or concentrated supernatant fluids (SF) supplemented with complete Freund adjuvant for the first and with incomplete Freund adjuvant for the three other injections. Sixty eight percent (P < 0.001) of mice vaccinated with 5 gg of extracellular D2EA102 protein were protected against lethal challenge (Delenda et al., 1994). Mice were challenged withDEN-2 virus (Delenda et al., 1994). Dengue Vaccine using Vaccinia Virus expressing M Protein VO_0011455 Recombinant vector vaccine Research Vaccinia virus [Ref1376:Bray and Lai, 1991]. Intraperitoneal injection (i.p.) Intraperitoneal injection (i.p.) Recombinant vector construction BALB/c BALB/c mice were immunized by i .p .inoculation of 107 p .f .u . of recombinant vaccinia virus expressing M protein (Bray and Lai, 1991). Mice immunized with the recombinant virus were protected against subsequent dengue 4 encephalitis challenge (Bray and Lai, 1991). The mice were challenged at age 6 weeks by intracardiac (i.c.) challenge of 100 LD50 of D4 virus, then observed 21 days for signs of encephalitis or death (Bray and Lai, 1991). Dengue Vaccine using Vaccinia Virus expressing prM Protein VO_0011452 Recombinant vector vaccine Research Vaccinia virus [Ref1376:Bray and Lai, 1991]. Intraperitoneal injection (i.p.) Intraperitoneal injection (i.p.) Recombinant vector construction BALB/c BALB/c mice were immunized by i .p .inoculation of 10^7 p .f .u . of recombinant vaccinia virus (Bray and Lai, 1991). Mice immunized with the recombinant virus were protected against subsequent dengue 4 encephalitis challenge (Bray and Lai, 1991). The mice were challenged at age 6 weeks by i .c challenge of 100 LD50 of D4 virus, then observed 21 days for signs of encephalitis or death (Bray and Lai, 1991). Dengue virus DNA vaccine 1040D2MEL encoding dengue-2 prM-E-LAMP chimeric protein VO_0004473 DNA vaccine Research pVR1040(Vical Inc.) [Ref2410:Raviprakash et al., 2001] Intramuscular injection (i.m.) GM-CSF (Raviprakash et al., 2001) Intramuscular injection (i.m.) E, prM, and LAMP from dengue virus 2 New Guinea C (Raviprakash et al., 2001) DNA vaccine construction DNA vaccine construction VO_0000286 When injected into mice, D2MEL elicited an enhanced antibody response compared to D2ME, which was further augmented by coimmunization with a plasmid expressing mouse granulocyte-monocyte colony stimulating factor (GM-CSF). Neutralizing antibodies are thought to be of paramount importance for protection against dengue disease (Raviprakash et al., 2001). Dengue virus DNA vaccine D1ME encoding prM and E VO_0004470 DNA vaccine Research pVR1012 (Vical Inc.) [Ref2407:Raviprakash et al., 2000] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pVR1012 expressed the dengue-1 pre-membrane (prM) and full-length envelope (E) genes (Raviprakash et al., 2000). DNA vaccine construction Vector pVR1012 (Vical Inc.) expressed the dengue-1 pre-membrane (prM) and full-length envelope (E) genes (Raviprakash et al., 2000). VO_0000286 Four of the eight i.m.-inoculated monkeys were protected completely from developing viraemia when challenged 4 months after the last dose with homologous dengue virus. The other four monkeys had reduced viraemia compared with the control immunized monkeys. The i.d. -inoculated monkeys showed no reduction in viraemia when challenged with the virus (Raviprakash et al., 2000). Dengue Virus DNA Vaccine D1ME-VRP VO_0004548 DNA vaccine Research D1ME-DNA [Ref2668:Chen et al., 2007] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction After the third dose of vaccine, all animals in the DDD group, VVV group, and DDV group had developed neutralizing antibodies. The dengue virus 1-specific IgG response to all vaccination regimens was predominantly of the IgG1 type, with smaller amounts of IgG2 and no measurable amounts of IgG4 (Chen et al., 2007). Monkeys were divided into groups DDD, VVV, DDV, and control and immunized with D1ME-DNA or D1ME-VRP as shown in the study design. D1ME-DNA was administered intramuscularly, with 0.5 ml given in each of the two upper arms. D1ME-VRP was delivered intramuscularly, as well (Chen et al., 2007). VO_0003057 All vaccination regimens showed significant protection from viremia compared to that of the unvaccinated control group (Chen et al., 2007). Twenty weeks after the final immunization, animals were challenged by subcutaneous injection of 10^5 PFU of live dengue virus 1 (Western Pacific 74 strain) in a 0.5-ml volume (Chen et al., 2007). Dengue Virus DNA Vaccine encoding NS1 VO_0004549 DNA vaccine Research pcTPANS1 [Ref2409:Costa et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) NS1 from dengue virus 2 strain NGC (Costa et al., 2006) DNA vaccine construction All Balb/c mice intramuscularly inoculated with the pcTPANS1 presented high levels of NS1-specifc antibodies (Costa et al., 2006). Male Balb/c mice, 4–6 weeks old, were intramuscularly injected in each hind limb tibialis anterior muscle with 50 μg of the pcTPANS1 or pcDNA3 plasmids dissolved in 50 μl of PBS (100 μg/dose/mice). Mice were inoculated with two DNA doses, given two weeks apart, and bled before immunization and 4 weeks after the first DNA dose (Costa et al., 2006). VO_0003057 Vaccinated animals were challenged with intracerebral DENV-2 virus inoculations and a 100% survival was observed (Costa et al., 2006). Two weeks after the second DNA dose, each immunized mouse was challenged with intracerebral inoculation with 30 μL of 4.32 log10 PFU of DENV2 (Costa et al., 2006). Dengue Virus DNA Vaccine expressing prM/E proteins VO_0004547 DNA vaccine Research DENV-4-DNAv [Ref2667:Lima et al., 2011] Intramuscular injection (i.m.) Intramuscular injection (i.m.) prM and E proteins from dengue virus 4 strain H241 (Lima et al., 2011) DNA vaccine construction DNA vaccine construction The animals immunized with DENV-4-DNAv produced rising levels, after each vaccine inoculation, of specific neutralizing antibodies against dengue-4 virus (Lima et al., 2011). Ten 5-week-old female BALB/c mice per immunization group were inoculated three times into the quadriceps muscle with 100 μg of DENV-4-DNAv or pCI (empty vector), DENV-4 heat inactivated (1 × 10^5 PFU), or PBS. The mice were primed on day 0 and boosted 15 and 30 days after the initial inoculation (Lima et al., 2011). VO_0003057 Immunization with DENV-4-DNAv induced significant protection against DENV-4 challenge, where 80% of the challenged mice survived (Lima et al., 2011). Fifteen days after the third inoculation, the mice were challenged intracerebrally with a dose of 100LD50, prepared from a DENV-4-infected suckling mouse brain. Mouse mortality was monitored daily for 21 days (Lima et al., 2011). Dengue virus DNA vaccine p1012D2ME encoding prM and E from DEN 2 New Guinea C strain VO_0004474 DNA vaccine Research pVR1012 (Vical Inc, San Diego, CA) [Ref2411:Porter et al., 1998] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction DNA vaccine construction VO_0000286 In a lethal mouse intracerebral challenge model, the vaccine provided a significant level of protection. Sixty percent of the mice immunized with the DEN DNA vaccine plus pUC 19 survived the challenge compared to only 10% in the control group that received vector plus pUC (Porter et al., 1998). Dengue virus DNA vaccine pcTPANS1 encoding NS1 fused to the tissue plasminogen activator signal sequence VO_0004472 DNA vaccine Research pcDNA3 [Ref2409:Costa et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pcDNA3 expressed the secretory signal sequence derived from human tissue plasminogen activator (t-PA) fused to the full length of the DENV-2 NS1 gene (Costa et al., 2006). VO_0000286 Vaccinated animals were challenged against DENV-2 in two murine models, based on intracerebral (i.c.) and intraperitoneal (i.p.) virus inoculations, and in both cases, pcTPANS1-immunized mice were protected (Costa et al., 2006). Dengue virus DNA vaccine pE1D2 encoding E from Dengue Virus 2 strain New Guinea C VO_0004471 DNA vaccine Research pcTPA plasmid , a modified pcDNA3 vector (Invitrogen) [Ref2408:Azevedo et al., 2011] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pcTPA plasmid , a modified pcDNA3 vector (Invitrogen) expressed amino acids 1–398 of the E protein (Azevedo et al., 2011). VO_0000286 All pE1D2-vaccinated mice survived challenge, while 45% of animals immunized with the pE2D2 died after infection. Furthermore, only 10% of pE1D2-immunized mice presented some clinical signs of infection after challenge, whereas most of animals inoculated with the pE2D2 showed effects of the disease with high morbidity degrees (Azevedo et al., 2011). Dengue virus DNA vaccine sA encoding prM and E from Dengue Virus 4 VO_0004466 DNA vaccine Research pMV10.1 [Ref2403:Raviprakash et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pMV10.1 expressed prM and E genes in which the N-terminal 90% of E gene was shuffled (Raviprakash et al., 2006). DNA vaccine construction Vector pMV10.1 expressed prM and E genes in which the N-terminal 90% of E gene was shuffled (Raviprakash et al., 2006). Five of six animals vaccinated developed antibodies that neutralized all 4 dengue serotypes in vitro (Raviprakash et al., 2006). VO_0000286 When challenged with live dengue-1 or dengue-2 virus, partial protection against dengue-1 was observed (Raviprakash et al., 2006). Dengue virus DNA vaccine sABC encoding prM and E VO_0004469 DNA vaccine Research pMV10.1 [Ref2403:Raviprakash et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pMV10.1 expressed premembrane and envelope genes of each of four serotypes of dengue viruses (Raviprakash et al., 2006). DNA vaccine construction Vector pMV10.1 expressed premembrane and envelope genes of each of four serotypes of dengue viruses (Raviprakash et al., 2006). DNA vaccine construction This combination vaccine encoded all the proteins from all 3 vaccines (Raviprakash et al., 2006). VO_0000286 When challenged with live dengue-1 or dengue-2 virus, partial protection against dengue-1 was observed. The best protection against dengue-1 viremia was demonstrated by the mixture of shuffled vaccines (sABC) out of all the vaccines tested (Raviprakash et al., 2006). Dengue virus DNA vaccine sB encoding E VO_0004467 DNA vaccine Research pMV10.1 [Ref2403:Raviprakash et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pMV10.1 expressed a shuffled truncated E protein (Raviprakash et al., 2006). VO_0000286 When challenged with live dengue-1 or dengue-2 virus, partial protection against dengue-1 was observed (Raviprakash et al., 2006). Dengue virus DNA vaccine sC encoding prM and E VO_0004468 DNA vaccine Research pMV10.1 [Ref2403:Raviprakash et al., 2006] Intramuscular injection (i.m.) Intramuscular injection (i.m.) DNA vaccine construction Vector pMV10.1 expressed prM and E genes in which the N-terminal 90% of E gene was shuffled.a shuffled truncated E protein (Raviprakash et al., 2006). DNA vaccine construction Vector pMV10.1 expressed prM and E genes in which the N-terminal 90% of E gene was shuffled.a shuffled truncated E protein (Raviprakash et al., 2006). Four of six animals vaccinated developed antibodies that neutralized all 4 dengue serotypes in vitro (Raviprakash et al., 2006). VO_0000286 When challenged with live dengue-1 or dengue-2 virus, partial protection against dengue-1 was observed (Raviprakash et al., 2006). Dengue Virus Vaccine TV005 Live, attenuated vaccine Clinical trial Intramuscular injection (i.m.) Live attenuated tetravalent vaccine TV005 protects humans against DEN2Δ30 (Tonga/74) challenge. (Hou et al., 2022) TV005 is an admixture composed of 4 DENV strains attenuated by a 30-nucleotide deletion in the 3′ UTR (rDEN1Δ30 and rDEN4Δ30), one 30-nucleotide and one-31 nucleotide deletion in the 3′ UTR (rDEN3Δ30/31), or by replacing the prM and E of rDEN4Δ30 with those of DENV2 NGC (rDEN2/4Δ30). (Hou et al., 2022) Intramuscular injection (i.m.) Live attenuated tetravalent dengue vaccine TV005 composed of rDEN1Δ30, rDEN2/4Δ30, rDEN3Δ30/31, and rDEN4Δ30. (Hou et al., 2022) Dengvaxia Dengvaxia® Sanofi Pasteur VO_0010342 Recombinant vector vaccine Licensed Intramuscular injection (i.m.) immunization implementation has been limited to subnational public health programs in Brazil and the Philippines Dengvaxia® is a live attenuated tetravalent vaccine consisting of chimeras made up of structural pre-membrane (prM) and envelope (E) genes of the four DENV types combined with the nonstructural genes of yellow fever 17D vaccine strain (chimeric yellow fever dengue – CYD) (Thomas and Yoon, 2019) none Intramuscular injection (i.m.) Recombinant vector construction Recombinant vector construction Recombinant vector construction Recombinant vector construction Recombinant vector construction Recombinant vector construction Recombinant vector construction Recombinant vector construction Recombinant vector construction Dengvaxia® is a live attenuated tetravalent vaccine consisting of chimeras made up of structural pre-membrane (prM) and envelope (E) genes of the four DENV types combined with the nonstructural genes of yellow fever 17D vaccine strain. (Thomas and Yoon, 2019) All groups were compared to the control group, Statistically significant difference in antibodies for all serotypes for month 7 and month 13 after injection was investigated. The results showed no statistically significant difference in antibodies for all serotypes at baseline (Villar et al., 2015). Healthy children between the ages of 9 and 16 years received three injections of recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) or placebo at months 0, 6, and 12 under blinded conditions. (Villar et al., 2015) Vaccine Efficacy for 176 cases of virologically confirmed dengue in the vaccine group and 221 in the control group that were diagnosed more than 28 days after the third dose (primary outcome): Serotype 1: 50.3%, Serotype 2: 42.3% , Serotype 3: 74.0%, Serotype 4: 77.7%. Vaccine Efficacy for all children who received at least one injection from month 0 to month 25: Serotype 1: 54.8%, Serotype 2: 50.2%, Serotype 3: 74.2%, Serotype 4: 80.9% (Villar et al., 2015). Four serious adverse events were deemed to be vaccine-related by investigators and sponsors: three in the vaccine group (a moderate asthma attack 16 hours after the first injection, allergic urticaria 4 hours after the second injection, and acute peripheral polyneuropathy associated with viral meningitis 3 days after the first injection, without detectable vaccine virus in samples, unspecified seizures 18 hours after the first injection, without detectable vaccine virus in samples,). All children recovered fully without sequelae. (Villar et al., 2015) licensed Dengue human vaccine Generic Unknown VO_0000725 Live, attenuated vaccine Licensed A generic representation of vaccines utilized to prevent Dengue Fever in humans, most commonly based on live, attenuated viruses that stimulate immune protection. These vaccines are designed to mimic natural infection while minimizing disease risk. rMV-TDV Recombinant vector vaccine Research Measles virus [Ref5901:Lin et al., 2020] Intraperitoneal injection (i.p.) rMV-TDV consists of two recombinant MV vectors carrying the genes encoding bivalent fusion envelope protein domain III (ED3) of DENV-1 and -3 or DENV-2 and -4. (Lin et al., 2020) Intraperitoneal injection (i.p.) Bivalent fusion envelope protein domain III (ED3) of DENV-1,2,3,4 (Lin et al., 2020) Recombinant vector construction domain 3 (Lin et al., 2020) Recombinant vector construction domain 3 (Lin et al., 2020) Recombinant protein preparation domain 3 (Lin et al., 2020) Recombinant vector construction domain 3 (Lin et al., 2020) A significant ED3-specific IgG response was induced after a single injection of rMV-TDV, but it was not observed in rMV-EGFP-immunized mice, and the response reached peak titers after the boost and was maintained at a high level for at least 20 weeks. A significant increase in neutralizing antibody titers (NT) to the 4 DENV serotypes was observed in rMV-TDV-immunized mice 8 weeks after vaccination compared to the rMV-EGFP controls. Only rMV-TDV- but not rMV-EGFP-immunized mice showed an obvious increase in the ED3-specific IFN-γ response dominated by DENV-3 after a single injection. Even 5 or 20 weeks later, the significantly higher level of DENV-3-specific IFN-γ responses were still maintained in rMV-TDV-immunized mice compared to the rMV-EGFP group. DENV-specific IL-4 responses were almost undetectable even after the boost. (Lin et al., 2020) Groups of 6-8-week-old AG-hCD46 mice were immunized intraperitoneally with rMV-TDV, a mixture containing 1 × 10^5 pfu of rMV-D13 and 1 × 10^5 pfu of rMV-D24, or 2 × 10^5 pfu of rMV-EGFP for the control. Mice were boosted with the same recombinant viruses and doses four weeks later. (Lin et al., 2020) . Consistent with the higher viremia and IFN-γ increase, TNF-α but not IL-6 or IL-10 was significantly increased in the peripheral blood cells of the rMV-EGFP controls at 3 days post challenge compared to those in rMV-TDV-immunized mice, which had no increase in inflammatory cytokines (p < 0.001). (Lin et al., 2020) Mice were challenged 4 weeks after the last immunization by subcutaneously injecting 1.5 × 107 ffu of wild-type DENV-2/16681. (Lin et al., 2020) YAC-CD46 mice, which carry the MV receptor-human CD46 transgene, were crossbred into AG129 mice to obtain AG-hCD46 transgenic mice (B6.129-Ifnar−/−, Ifngr−/− Tg(CD46)). (Lin et al., 2020) TAK-003 DENVax Live, attenuated vaccine Clinical trial Intramuscular injection (i.m.) (Torres-Flores et al., 2022)Tak-003/DENVax is based on a live-attenuated DENV-2 strain (PDK-53-V) in which the pre-membrane (prM) and envelope (E) genes of YFV have been replaced by the homologous genes from each one of the four DENV serotypes Intramuscular injection (i.m.) whole virus (DENV2) and prM/E (serotypes 1 - 4) (Torres-Flores et al., 2022) Of the 20,071 participants who were given at least one dose of vaccine or placebo (safety population), 19,021 (94.8%) received both injections and were included in the per-protocol analysis. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group). In the per-protocol analyses, vaccine efficacy was 80.2% (95% CI, 73.3 to 85.3; 61 cases of virologically confirmed dengue in the vaccine group vs. 149 cases in the placebo group), with 95.4% efficacy against dengue leading to hospitalization (95% CI, 88.4 to 98.2; 5 hospitalizations in the vaccine group vs. 53 hospitalizations in the placebo group). Planned exploratory analyses involving the 27.7% of the per-protocol population that was seronegative at baseline showed vaccine efficacy of 74.9% (95% CI, 57.0 to 85.4; 20 cases of virologically confirmed dengue in the vaccine group vs. 39 cases in the placebo group). (Biswal et al., 2019) Healthy children and adolescents 4 to 16 years of age in regions of Asia and Latin America were randomly assigned in a 2:1 ratio (stratified according to age category and region) to receive two doses of vaccine or placebo 3 months apart. (Biswal et al., 2019) The incidence of serious adverse events was similar in the vaccine group and placebo group (3.1% and 3.8%, respectively) (Biswal et al., 2019) TV003/TV005 Laboratory of Infectious Diseases (LID) of the National Institute of Allergy and Infectious Diseases (NIAID) Live, attenuated vaccine Clinical trial Intramuscular injection (i.m.) (Torres-Flores et al., 2022)TV003/TV005 was constructed by a deletion of 30 nucleotides (172–143) in the TL2 stem-loop of the 3′-UTR of DENV-4 and DENV-1 (rDEN4∆30 and rDEN1∆30), DENV-2 and DENV-3 components were constructed from the rDEN4∆30 backbone Intramuscular injection (i.m.) Against any serotype, efficacy was 80.2% in the per-protocol population (95% confidence interval [CI], 73.3 to 85.3; P<0.001; 61 cases of virologically confirmed dengue in the vaccine group and 149 in the placebo group). For specific serotypes; efficacious for DENV-2,3, and 1. 97.7% efficacy against DENV-2, 73.7% efficacy against DENV-1, and 62.6% efficacy against DENV-3; Inconclusive against DENV-4. The overall vaccine efficacy in the safety population was 80.9% (95% confidence interval [CI], 75.2 to 85.3; 78 cases per 13,380 [0.5 per 100 person-years] in the vaccine group vs. 199 cases per 6687 [2.5 per 100 person-years] in the placebo group) (Biswal et al., 2019). The lyophilized vaccine formulation was reconstituted before administration. One 0.5-ml dose of TAK-003 contained approximately 3.6, 4.0, 4.6, and 5.1 log10 plaque-forming units of TDV-1, TDV-2, TDV-3, and TDV-4, respectively. The placebo was a 0.5-ml injection of saline. Vaccine and placebo were administered subcutaneously into the upper arm (Biswal et al., 2019). V180 - Aluminum Hydroxide Alhydrogel™ Adjuvant Subunit vaccine Clinical trial Intramuscular injection (i.m.) A recombinant subunit Dengue Virus vaccine that utilizes 80% of the Envelope protein of all 4 serotypes as the antigen with aluminum hydroxide adjuvant. Aluminum Hydroxide Alhydrogel™ (Manoff et al., 2019) Intramuscular injection (i.m.) Truncated dengue envelope proteins (DEN-80E) for all 4 serotypes (Manoff et al., 2019) Recombinant protein preparation Truncated versions of E consisting of the N-terminal portion of E (DEN-80E) for all 4 serotypes. (Manoff et al., 2019) Recombinant protein preparation Truncated versions of E consisting of the N-terminal portion of E (DEN-80E) for all 4 serotypes. (Manoff et al., 2019) Recombinant protein preparation Truncated versions of E consisting of the N-terminal portion of E (DEN-80E) for all 4 serotypes. (Manoff et al., 2019) Recombinant protein preparation Truncated versions of E consisting of the N-terminal portion of E (DEN-80E) for all 4 serotypes. (Manoff et al., 2019) The medium-dose V180 formulation with Alhydrogel™ did not meet the pre-specified definition of a positive immune response, but showed limited evidence of immunogenicity for all 4 serotypes: SCRs ranged from 14.3 to 62.5%, while GMTs ranged from <10 to 20. For the medium-dose V180 formulation with Alhydrogel™, GMTs for some serotypes increased by Month 3, and then returned to baseline by Month 8 (6 Months Postdose 3).Tetravalent or ≥trivalent responses were exhibited by lower proportions of recipients of medium-dose V180 with Alhydrogel. (Manoff et al., 2019) Among the 98 adults who were randomized into the trial, 57 (58%) were female, 92 (94%) were white, and the mean age was 27 years (range, 18 to 48 years). The gender, race/ethnicity, and age distributions were generally consistent across the treatment groups.The first, second, and third injections of trial product were received by 98 (100%), 94 (96%), and 90 (92%) of randomized participants, respectively. Overall, 83 (85%) participants completed the trial. (Manoff et al., 2019) For all 4 treatment types, pain/tenderness was the most frequent injection-site AE, followed by erythema and swelling. Fever (temperature ≥38.0°C [100.4°F]) was reported in 0 (0%) Alhydrogel™ recipients. (Manoff et al., 2019) V180 - ISCOMATRIX™ adjuvant investigational recombinant subunit vaccine Clinical trial Intramuscular injection (i.m.) A recombinant subunit Dengue Virus vaccine that utilizes 80% of the Envelope protein of all 4 serotypes as the antigen with ISCOMATRIX™ adjuvant (Manoff et al., 2019). Saponin-based ISCOMATRIX™ adjuvant (Manoff et al., 2019) Intramuscular injection (i.m.) Truncated dengue envelope proteins (DEN-80E) for all 4 serotypes (Manoff et al., 2019) Virus Neutralizing Antibody: Each of the 6 V180 formulations containing ISCOMATRIX™ adjuvant met the pre-specified definition of a positive immune response, with seroconversion rates of ≥85.7% for all 4 dengue serotypes; GMTs ranged from 73 to 1344. Within each V180 dose level, GMTs were slightly higher (within 2-fold) for formulations with 60 ISCO™ units than formulations with 30 ISCO™ units. In contrast, for a given dose level of ISCOMATRIX™ adjuvant, GMTs did not increase with increasing doses of V180 antigen. All 6 V180 formulations with ISCOMATRIX™ adjuvant had similar profiles: GMTs increased by Month 2 (28 Days Postdose 2), increased further by Month 3 (28 Days Postdose 3), and then declined over time through Month 14 (1 Year Postdose 3), remaining generally above baseline for DENV1, DENV2, and DENV3, and generally returning to baseline for DENV4. During long-term follow-up, GMTs generally remained higher in the 60 ISCO™ unit group than the 30 ISCO™ unit group for the low-dose V180 cohort, but tended to converge in the medium-dose and high-dose V180 cohorts. Memory B-Cell Responses: Induction of B-cell memory to each of the four DENV serotypes was observed in peripheral blood mononuclear cells among all participants who received 3 injections of high-dose V180 with ISCOMATRIX™ adjuvant (30 or 60 ISCO™ units) at 28 Days Postdose 3, the mean number of dengue-specific memory B cells in these recipients had increased in frequency by 1 to 2 logs over the pre-vaccination baseline (Manoff et al., 2019) Among the 98 adults who were randomized into the trial, 57 (58%) were female, 92 (94%) were white, and the mean age was 27 years (range, 18 to 48 years). The gender, race/ethnicity, and age distributions were generally consistent across the treatment groups (data not shown).The first, second, and third injections of trial product were received by 98 (100%), 94 (96%), and 90 (92%) of randomized participants, respectively (Figure 1). Overall, 83 (85%) participants completed the trial. (Manoff et al., 2019) V180 with ISCOMATRIX™ adjuvant was associated with a higher frequency of injection-site AEs (adverse effects) overall, injection-site AEs of erythema or swelling that were ≥5 cm or ≥10 cm, and a higher frequency of injection-site pain/tenderness that participants assessed as severe (defined in the protocol as the inability to do work or usual activities). V180 with ISCOMATRIX™ adjuvant was also associated with higher frequencies of systemic AEs overall, and those assessed by the investigator as related to study product. Fever (temperature ≥38.0°C [100.4°F]) was reported in 5 (9%) ISCOMATRIX™ adjuvant recipients. (Manoff et al., 2019) V180 - unadjuvanted investigational recombinant subunit vaccine Clinical trial Intramuscular injection (i.m.) A recombinant subunit Dengue Virus vaccine that utilizes 80% of the Envelope protein of all 4 serotypes as the antigen (Manoff et al., 2019). Intramuscular injection (i.m.) Truncated dengue envelope proteins (DEN-80E) for all 4 serotypes (Manoff et al., 2019) Virus-Neutralizing Antibody: The unadjuvanted high-dose V180 formulation did not meet the pre-specified definition of a positive immune response, but showed limited evidence of immunogenicity for all 4 serotypes: SCRs ranged from 14.3 to 62.5%, while GMTs ranged from <10 to 20. There was no detectable immune response in the unadjuvanted medium-dose V180 group or the placebo group. For the unadjuvanted high-dose V180 formulation, GMTs for some serotypes increased by Month 3, and then returned to baseline by Month 8 (6 Months Postdose 3). Tetravalent or ≥trivalent responses were exhibited by lower proportions of recipients of high-dose unadjuvanted V180, and by no recipients of medium-dose unadjuvanted V180. In the majority of instances when participants had FRNT50 titers ≥10 for only 3 seotypes, DENV4 was the serotype with a titer <10. Memory B-Cell Responses: The mean change ranged from a 0.4-log decrease to 1-log increase among recipients of unadjuvanted high-dose V180, and generally increased <1 log among placebo recipients. (Manoff et al., 2019) Among the 98 adults who were randomized into the trial, 57 (58%) were female, 92 (94%) were white, and the mean age was 27 years (range, 18 to 48 years). The gender, race/ethnicity, and age distributions were generally consistent across the treatment groups. The first, second, and third injections of trial product were received by 98 (100%), 94 (96%), and 90 (92%) of randomized participants, respectively. Overall, 83 (85%) participants completed the trial. (Manoff et al., 2019) For all 4 treatment types, pain/tenderness was the most frequent injection-site AE, followed by erythema and swelling. Fever (temperature ≥38.0°C [100.4°F]) was reported in 0 (0%) unadujuvanted recipients. (Manoff et al., 2019) 18H6 synthetic E protein synthetic construct 73915390 73915391 AAZ92557.1 CDD:279241 CDD:280922 CDD:213897 32630 ? chimeric Dengue envelope antigen 18H6 7.33 46583.77 549 derived from Dengue virus >gi|73915390|gb|DQ158253.1| Synthetic construct chimeric Dengue envelope antigen 18H6 mRNA, partial cds ATGGTGGTGATCTTCATCCTGCTGATGCTGGTGACCCCCTCCATGACAATGAGGTGCGTGGGCGTGGGCA ACAGGGACTTCGTGGAGGGCCTGAGCGGCGCCACCTGGGTGGACGTGGTGCTGGAGCACGGCGGCTGCGT GACCACCATGGCCAAGAACAAGCCCACCCTGGACTTCGAGCTGATCAAGACCACCGCCAAGGAGGTGGCC CTGCTGAGGACCTACTGCATCGAGGCCAGCATCAGCAACATCACCACCGCCACCAGGTGCCCCACCCAGG GCGAGGCCATCCTGCCCGAGGAGCAGGACCAGAACTACGTGTGCAAGCACACCTACGTGGACAGGGGCTG GGGCAACGGCTGCGGCCTGTTCGGCAAGGGCAGCCTGGTGACCTGCGCCAAGTTCACCTGCAAGAAGAAC ATGGAGGGCAACATCGTGCAGCCCGAGAACCTGGAGTACACCATCGTGATCACCCCCCACACCGGCGACC AGCACCAGGTGGGCAACGACACCCAGGGCGTGACCGTGGAGATCACCCCCCAGGCCAGCACCGTGGAGGC CATCCTGCCCGAGTACGGCACCCTGGGCCTGGAGTGCAGCCCCAGGACTGGCCTGGACTTCAACAGGGTG GTGCTGCTGACCATGAAGAAGAAGAGCTGGCTGGTGCACAAGCAGTGGTTCCTGGACCTGCCCCTGCCCT GGACCGCCGGCGCCGACACCAGCGAGGTGCACTGGAACCACAAGGAGAGGATGGTGACCTTCAAGAACGC CCACGCCAAGAGGCAGGACGTGACCGTGCTGGGCAGCCAGGAGGGCGCCATGCACAGCGCCCTGGCCGGC GCCACCGAGATCCAGATGAGCAGCGGCAACCTGCTGTTCACCGGCCACCTGAAGTGCAGGCTGAAGATGG ACAAGCTGCAGCTGAAGGGCGTGAGCTACGTGATGTGCACCGGCAGCTTCAAGCTGGAGAAGGAGGTGGC CGAGACCCAGCACGGCACCGTGCTGGTGCAGGTGAAGTACGAGGGCACCGACGCCCCCTGCAAGATCCCC TTCAGCACCGAGGACGGCCAGGGCAAGGCCCACAACGGCAGGCTGATCACCGTGAACCCCATCGTGATCG ACAAGGAGAAGCCCGTGAACATCGAGCTGGAGCCCCCCTTCGGCGAGAGCTACATCGTGGTGGGCGCCGG CGAGAAGGCCCTGAAGCTGAGCTGGTTCAAGAAGGGCAGCAGCATCGGCAAGATGTTCGAGGCCACCGCC AGGGGCGCCAAGAGGATGGCCATCCTGGGCGAGACCGCCTGGGACTTCGGCAGCGTGGGCGGCCTGCTGA CCAGCCTGGGCAAGGCCGTGCACCAGGTGTTCGGCGCCATCTACGGCGCC >AAZ92557.1 chimeric Dengue envelope antigen 18H6, partial [synthetic construct] MVVIFILLMLVTPSMTMRCVGVGNRDFVEGLSGATWVDVVLEHGGCVTTMAKNKPTLDFELIKTTAKEVA LLRTYCIEASISNITTATRCPTQGEAILPEEQDQNYVCKHTYVDRGWGNGCGLFGKGSLVTCAKFTCKKN MEGNIVQPENLEYTIVITPHTGDQHQVGNDTQGVTVEITPQASTVEAILPEYGTLGLECSPRTGLDFNRV VLLTMKKKSWLVHKQWFLDLPLPWTAGADTSEVHWNHKERMVTFKNAHAKRQDVTVLGSQEGAMHSALAG ATEIQMSSGNLLFTGHLKCRLKMDKLQLKGVSYVMCTGSFKLEKEVAETQHGTVLVQVKYEGTDAPCKIP FSTEDGQGKAHNGRLITVNPIVIDKEKPVNIELEPPFGESYIVVGAGEKALKLSWFKKGSSIGKMFEATA RGAKRMAILGETAWDFGSVGGLLTSLGKAVHQVFGAIYGA Protective antigen E from Dengue virus 1 Dengue virus 1 148372385 CDD:279241 CDD:332896 CDD:213392 CDD:213897 11053 ? envelope protein 7.42 50024.4 559 Flavivirus glycoprotein, central and dimerisation domains; pfam00869 >ABQ63116.1 envelope protein, partial [Dengue virus 1] MRCVGIGSRDFVEGLSGATWVDVVLEHGSCVTTMAKDKPTLDIELLKTEVTNPAVLRKLCIEAKISNTTT DSRCPTQGEATLVEEQDANFVCRRTFVDRGWGNGCGLFGKGSLITCAKFKCVTKLEGKIVQYENLKYSVI VTVHTGDQHQVGNESTEHGTTATITPQAPTTEIQLTDYGALTLDCSPRTGLDFNEMVLLTMKEKSWLVHK QWFLDLPLPWTSGASTSQETWNRQDLLVTFKTAHAKKQEVVVLGSQEGAMHTALTGATEIQTSGTTTIFA GHLKCRLKMDKLTLKGMSYVMCTGSFKLEKEVAETQHGTVLVQIKYEGTDAPCKIPFSTQDEKGVTQNGR LITANPIVTDKEKPVNIEAEPPFGESYIVIGAGEKALKLSWFKKGSSIGKMFEATARGARRMAILGDTAW DFGSIGGVFTSVGKLVHQIFGTAYGVLFSGVSWTMKIGIGVLLTWLGLNSRSTSLSMTCIAVGLVTLYLG VMVQA Protective antigen E from Dengue virus 3 Dengue virus 3 166092240 CDD:279241 CDD:280922 CDD:213897 11069 ? envelope 7.27 50375.82 549 genotype: I >ABY82135.1 envelope, partial [Dengue virus 3] MRCVGVGNRDFVEGLSGATWVDVVLEHGGCVTTMAKNKPTLDIELQKTEATQLATLRKLCIEGKITNVTT DSRCPTQGEAILPEEQDQNYVCKHTYVDRGWGNGCGLFGKGSLVTCAKFQCLESIEGKAVQHENLKYTVI ITVHTGDQHQVGNETQGVTAEITPQASTVEAILPEYGTLGLECSPRTGLDFNEMILLTMKNKAWMVHRQW FFDLPLPWTSGATTETPTWNKKELLVTFKNAHAKKQEVVVLGSQEGAMHTALTGATEIQTSGGTSIFAGH LKCRLKMDKLELKGMSYAMCLNAFVLKKEVSETQHGTILIKVEYKGEDAPCKIPFSTEDGQGKAHNGRLI TANPIVTKKEEPVNIEAEPPFGESNIVIGIGDKALKINWYKKGSSIGKMFEATARGARRMAILGDTAWDF GSVGGVLNSLGKMVHQIFGSAYTALFSGVSWIMKIGIGVLLTWIGLNSKNTSMSFSCIVIGIITLYLGAV VQA Protective antigen E from Dengue virus 4 Dengue virus 4 369726339 CDD:279241 CDD:213392 CDD:213897 11070 ? envelope protein 7.29 49911.732 559 type: Dengue virus; genotype: IIa >AEX20298.1 envelope protein, partial [Dengue virus 4] MRCVGVGNRDFVEGVSGGAWVDLVLEHGGCVTTMAQGKPTLDFELTKTTAKEVALLRTYCIEASISNITT ATRCPTQGEPYLKEEQDQQYICRRDVVDRGWGNGCGLFGKGGVVTCAKFLCSGKITGNLVQIENLEYTVV VTVHNGDTHAVGNDTSNHGVTATITPRSPSVEVKLPDYGELTLDCEPRSGIDFNEMILMKMKKKTWLVHK QWFLDLPLPWTAGADTSEVHWNYKERMVTFKVPHAKRQDVTVLGSQEGAMHSALAGATEVDSGDGNHMFA GHLKCKVRMEKLRIKGMSYTMCSGKFSIDKEMAETQHGTTVVKVKYEGAGAPCKIPIEIRDVNKEKVVGR IISSTPFAENTNSVINIELEPPFGDSYIVIGVGDSALTLHWFRKGSSIGKMFESTYRGAKRMAILGETAW DFGSVGGLFTSLGKAVHQVFGSVYTTMFGGVSWMIRILIGFLVLWIGTNSRNTSMAMTCIAVGGITLFLG FTVQA Protective antigen E protein from Dengue Virus 2 VO_0011311 202078796 1OAN CDD:279241 CDD:213392 CDD:213897 11060 ? envelope protein 7.67 50568.28 559 Flavivirus glycoprotein, central and dimerisation domains; pfam00869 >ACH96447.1 envelope protein, partial [Dengue virus 2] MRCIGISNRDFVEGVSGGSWVDIVLEHGSCVTTMAKNKPTLDFELIKTEAKHPATLRKYCIEAKLTNTTT ASRCPTQGEPSLNEEQDKRFVCKHSMVDRGWGNGCGLFGKGGIVTCAMFTCKKNMEGKIVQPENLEYTIV ITPHSGEENAVGNDTGKHGKEIKVTPQSSITEAELTGYGTVTMECSPRTGLDFNEMVLLQMENKAWLVHR QWFLDLPLPWLPGADTQGSNWIQKETLVTFKNPHAKKQDVVVLGSQEGAMHTALTGATEIQMSSGNLLFT GHLKCRLRMDKLQLKGMSYSMCTGKFKVVKEIAETQHGTIVVRVQYEGDGSPCKIPFEIMDLEKRHVLGR LITVNPIVTEKDSPVNIEAEPPFGDSYIIIGVEPGQLKLSWFKKGSSIGQMFETTMRGAKRMAILGDTAW DFGSLGGVFTSIGKALHQVFGAIYGAAFSGVSWTMKILIGVVITWIGMNSRSTSLSVSLVLVGVVTLYLG VMVQA Protective antigen A recombinant baculovirus encoding a dengue (DEN)-2 virus envelope glycoprotein truncated of 102 amino acids (aa) at its C-terminus (D2EA102) was constructed. Both intracellular and extracellular D2EA102 induced neutralizing antibodies in mice and were thus immunogenic. Sixty eight percent (P < 0.001) of mice vaccinated with 5 gg of extracellular D2EA102 protein were protected against lethal challenge [Ref1371:Delenda et al., 1994]. M protein VO_0011316 73671170 CDD:279358 11070 ? membrane (M) protein 7.7 8254.03 129 Flavivirus envelope glycoprotein M; pfam01004 >NP_740316.1 membrane (M) protein [Dengue virus 4] SVALTPHSGMGLETRAETWMSSEGAWKHAQRVESWILRNPGFALLAGFMAYMIGQTGIQRTVFFVLMMLV APSYG Protective antigen A recombinant vaccinia virus that expressed the M protein of Dengue 4 virus was constructed. Mice immunized with the recombinant virus were protected against subsequent dengue 4 encephalitis challenge [Ref1376:Bray and Lai, 1991]. NS1 VO_0011312 288848 CDD:213897 CDD:279316 InterPro:IPR001157 UniProtKB/TrEMBL:Q06371 11060 ? 7.2 41028.15 429 flavivirus envelope glycoprotein E, stem/anchor domain; TIGR04240 >CAA78918.1 NS1, partial [Dengue virus 2] MNSRSTSLSVSQVLVGIVTLYLGVMVQADSGCVVSWKNKELKCGSGIFVTDNVHTRTEQYKFQPESPSKL ASAIQKAHEEGICGIRSVTRLENLMWKQITSELNHILSENEVKLTIMTGDIKGIMQVGKRSLRPQPTELR YSWKTWGKAKMLSTELHNQTFLIDGPETAECPNTNRAWNSLEVEDYGFGVFTTNIWLRLREKQDAFCDSK LMSAAIKDNRAVHADMGYWIESALNDTWKIEKASFIEVKSCHWPKSHTLWSNGVLESEMVIPKNFAGPKS QHNNRPGYHTQTAGPWHLGKLEMDFDFCEGTTVVVTEDCGNRGPSLRTTTASGKLITEWCCRSCTLPPLR YRGEDGCWYGMEIRPLKEKEENLVSSLVTA Protective antigen The protective efficacy and immune responses of mice intramuscularly injected with plasmid encoding DEN-2 non-structural protein 1 (NS1) was evaluated. Intravenously challenged by lethal DEN-2, mice vaccinated with NS1-DNA exhibited a delay onset of paralysis, a marked decrease of morbidity, and a significant enhancement of survival [Ref1374:Wu et al., 2003]. POLY Yellow fever virus 1502173 9627245 YFVgp1 X03700 NP_041726 11089 0 10861 + mRNA 8.51 351142.06 3411 >NC_002031.1:1-10861 Yellow fever virus, complete genome AGTAAATCCTGTGTGCTAATTGAGGTGCATTGGTCTGCAAATCGAGTTGCTAGGCAATAAACACATTTGG ATTAATTTTAATCGTTCGTTGAGCGATTAGCAGAGAACTGACCAGAACATGTCTGGTCGTAAAGCTCAGG GAAAAACCCTGGGCGTCAATATGGTACGACGAGGAGTTCGCTCCTTGTCAAACAAAATAAAACAAAAAAC AAAACAAATTGGAAACAGACCTGGACCTTCAAGAGGTGTTCAAGGATTTATCTTTTTCTTTTTGTTCAAC ATTTTGACTGGAAAAAAGATCACAGCCCACCTAAAGAGGTTGTGGAAAATGCTGGACCCAAGACAAGGCT TGGCTGTTCTAAGGAAAGTCAAGAGAGTGGTGGCCAGTTTGATGAGAGGATTGTCCTCAAGGAAACGCCG TTCCCATGATGTTCTGACTGTGCAATTCCTAATTTTGGGAATGCTGTTGATGACGGGTGGAGTGACCTTG GTGCGGAAAAACAGATGGTTGCTCCTAAATGTGACATCTGAGGACCTCGGGAAAACATTCTCTGTGGGCA CAGGCAACTGCACAACAAACATTTTGGAAGCCAAGTACTGGTGCCCAGACTCAATGGAATACAACTGTCC CAATCTCAGTCCAAGAGAGGAGCCAGATGACATTGATTGCTGGTGCTATGGGGTGGAAAACGTTAGAGTC GCATATGGTAAGTGTGACTCAGCAGGCAGGTCTAGGAGGTCAAGAAGGGCCATTGACTTGCCTACGCATG AAAACCATGGTTTGAAGACCCGGCAAGAAAAATGGATGACTGGAAGAATGGGTGAAAGGCAACTCCAAAA GATTGAGAGATGGTTCGTGAGGAACCCCTTTTTTGCAGTGACGGCTCTGACCATTGCCTACCTTGTGGGA AGCAACATGACGCAACGAGTCGTGATTGCCCTACTGGTCTTGGCTGTTGGTCCGGCCTACTCAGCTCACT GCATTGGAATTACTGACAGGGATTTCATTGAGGGGGTGCATGGAGGAACTTGGGTTTCAGCTACCCTGGA GCAAGACAAGTGTGTCACTGTTATGGCCCCTGACAAGCCTTCATTGGACATCTCACTAGAGACAGTAGCC ATTGATAGACCTGCTGAGGTGAGGAAAGTGTGTTACAATGCAGTTCTCACTCATGTGAAGATTAATGACA AGTGCCCCAGCACTGGAGAGGCCCACCTAGCTGAAGAGAACGAAGGGGACAATGCGTGCAAGCGCACTTA TTCTGATAGAGGCTGGGGCAATGGCTGTGGCCTATTTGGGAAAGGGAGCATTGTGGCATGCGCCAAATTC ACTTGTGCCAAATCCATGAGTTTGTTTGAGGTTGATCAGACCAAAATTCAGTATGTCATCAGAGCACAAT TGCATGTAGGGGCCAAGCAGGAAAATTGGAATACCGACATTAAGACTCTCAAGTTTGATGCCCTGTCAGG CTCCCAGGAAGTCGAGTTCATTGGGTATGGAAAAGCTACACTGGAATGCCAGGTGCAAACTGCGGTGGAC TTTGGTAACAGTTACATCGCTGAGATGGAAACAGAGAGCTGGATAGTGGACAGACAGTGGGCCCAGGACT TGACCCTGCCATGGCAGAGTGGAAGTGGCGGGGTGTGGAGAGAGATGCATCATCTTGTCGAATTTGAACC TCCGCATGCCGCCACTATCAGAGTACTGGCCCTGGGAAACCAGGAAGGCTCCTTGAAAACAGCTCTTACT GGCGCAATGAGGGTTACAAAGGACACAAATGACAACAACCTTTACAAACTACATGGTGGACATGTTTCTT GCAGAGTGAAATTGTCAGCTTTGACACTCAAGGGGACATCCTACAAAATATGCACTGACAAAATGTTTTT TGTCAAGAACCCAACTGACACTGGCCATGGCACTGTTGTGATGCAGGTGAAAGTGTCAAAAGGAGCCCCC TGCAGGATTCCAGTGATAGTAGCTGATGATCTTACAGCGGCAATCAATAAAGGCATTTTGGTTACAGTTA ACCCCATCGCCTCAACCAATGATGATGAAGTGCTGATTGAGGTGAACCCACCTTTTGGAGACAGCTACAT TATCGTTGGGAGAGGAGATTCACGTCTCACTTACCAGTGGCACAAAGAGGGAAGCTCAATAGGAAAGTTG TTCACTCAGACCATGAAAGGCGTGGAACGCCTGGCCGTCATGGGAGACACCGCCTGGGATTTCAGCTCCG CTGGAGGGTTCTTCACTTCGGTTGGGAAAGGAATTCATACGGTGTTTGGCTCTGCCTTTCAGGGGCTATT TGGCGGCTTGAACTGGATAACAAAGGTCATCATGGGGGCGGTACTTATATGGGTTGGCATCAACACAAGA AACATGACAATGTCCATGAGCATGATCTTGGTAGGAGTGATCATGATGTTTTTGTCTCTAGGAGTTGGGG CGGATCAAGGATGCGCCATCAACTTTGGCAAGAGAGAGCTCAAGTGCGGAGATGGTATCTTCATATTTAG AGACTCTGATGACTGGCTGAACAAGTACTCATACTATCCAGAAGATCCTGTGAAGCTTGCATCAATAGTG AAAGCCTCTTTTGAAGAAGGGAAGTGTGGCCTAAATTCAGTTGACTCCCTTGAGCATGAGATGTGGAGAA GCAGGGCAGATGAGATCAATGCCATTTTTGAGGAAAACGAGGTGGACATTTCTGTTGTCGTGCAGGATCC AAAGAATGTTTACCAGAGAGGAACTCATCCATTTTCCAGAATTCGGGATGGTCTGCAGTATGGTTGGAAG ACTTGGGGTAAGAACCTTGTGTTCTCCCCAGGGAGGAAGAATGGAAGCTTCATCATAGATGGAAAGTCCA GGAAAGAATGCCCGTTTTCAAACCGGGTCTGGAATTCTTTCCAGATAGAGGAGTTTGGGACGGGAGTGTT CACCACACGCGTGTACATGGACGCAGTCTTTGAATACACCATAGACTGCGATGGATCTATCTTGGGTGCA GCGGTGAACGGAAAAAAGAGTGCCCATGGCTCTCCAACATTTTGGATGGGAAGTCATGAAGTAAATGGGA CATGGATGATCCACACCTTGGAGGCATTAGATTACAAGGAGTGTGAGTGGCCACTGACACATACGATTGG AACATCAGTTGAAGAGAGTGAAATGTTCATGCCGAGATCAATCGGAGGCCCAGTTAGCTCTCACAATCAT ATCCCTGGATACAAGGTTCAGACGAACGGACCTTGGATGCAGGTACCACTAGAAGTGAAGAGAGAAGCTT GCCCAGGGACTAGCGTGATCATTGATGGCAACTGTGATGGACGGGGAAAATCAACCAGATCCACCACGGA TAGCGGGAAAGTTATTCCTGAATGGTGTTGCCGCTCCTGCACAATGCCGCCTGTGAGCTTCCATGGTAGT GATGGGTGTTGGTATCCCATGGAAATTAGGCCAAGGAAAACGCATGAAAGCCATCTGGTGCGCTCCTGGG TTACAGCTGGAGAAATACATGCTGTCCCTTTTGGTTTGGTGAGCATGATGATAGCAATGGAAGTGGTCCT AAGGAAAAGACAGGGACCAAAGCAAATGTTGGTTGGAGGAGTAGTGCTCTTGGGAGCAATGCTGGTCGGG CAAGTAACTCTCCTTGATTTGCTGAAACTCACAGTGGCTGTGGGATTGCATTTCCATGAGATGAACAATG GAGGAGACGCCATGTATATGGCGTTGATTGCTGCCTTTTCAATCAGACCAGGGCTGCTCATCGGCTTTGG GCTCAGGACCCTATGGAGCCCTCGGGAACGCCTTGTGCTGACCCTAGGAGCAGCCATGGTGGAGATTGCC TTGGGTGGCGTGATGGGCGGCCTGTGGAAGTATCTAAATGCAGTTTCTCTCTGCATCCTGACAATAAATG CTGTTGCTTCTAGGAAAGCATCAAATACCATCTTGCCCCTCATGGCTCTGTTGACACCTGTCACTATGGC TGAGGTGAGACTTGCCGCAATGTTCTTTTGTGCCGTGGTTATCATAGGGGTCCTTCACCAGAATTTCAAG GACACCTCCATGCAGAAGACTATACCTCTGGTGGCCCTCACACTCACATCTTACCTGGGCTTGACACAAC CTTTTTTGGGCCTGTGTGCATTTCTGGCAACCCGCATATTTGGGCGAAGGAGTATCCCAGTGAATGAGGC ACTCGCAGCAGCTGGTCTAGTGGGAGTGCTGGCAGGACTGGCTTTTCAGGAGATGGAGAACTTCCTTGGT CCGATTGCAGTTGGAGGACTCCTGATGATGCTGGTTAGCGTGGCTGGGAGGGTGGATGGGCTAGAGCTCA AGAAGCTTGGTGAAGTTTCATGGGAAGAGGAGGCGGAGATCAGCGGGAGTTCCGCCCGCTATGATGTGGC ACTCAGTGAACAAGGGGAGTTCAAGCTGCTTTCTGAAGAGAAAGTGCCATGGGACCAGGTTGTGATGACC TCGCTGGCCTTGGTTGGGGCTGCCCTCCATCCATTTGCTCTTCTGCTGGTCCTTGCTGGGTGGCTGTTTC ATGTCAGGGGAGCTAGGAGAAGTGGGGATGTCTTGTGGGATATTCCCACTCCTAAGATCATCGAGGAATG TGAACATCTGGAGGATGGGATTTATGGCATATTCCAGTCAACCTTCTTGGGGGCCTCCCAGCGAGGAGTG GGAGTGGCACAGGGAGGGGTGTTCCACACAATGTGGCATGTCACAAGAGGAGCTTTCCTTGTCAGGAATG GCAAGAAGTTGATTCCATCTTGGGCTTCAGTAAAGGAAGACCTTGTCGCCTATGGTGGCTCATGGAAGTT GGAAGGCAGATGGGATGGAGAGGAAGAGGTCCAGTTGATCGCGGCTGTTCCAGGAAAGAACGTGGTCAAC GTCCAGACAAAACCGAGCTTGTTCAAAGTGAGGAATGGGGGAGAAATCGGGGCTGTCGCTCTTGACTATC CGAGTGGCACTTCAGGATCTCCTATTGTTAACAGGAACGGAGAGGTGATTGGGCTGTACGGCAATGGCAT CCTTGTCGGTGACAACTCCTTCGTGTCCGCCATATCCCAGACTGAGGTGAAGGAAGAAGGAAAGGAGGAG CTCCAAGAGATCCCGACAATGCTAAAGAAAGGAATGACAACTGTCCTTGATTTTCATCCTGGAGCTGGGA AGACAAGACGTTTCCTCCCACAGATCTTGGCCGAGTGCGCACGGAGACGCTTGCGCACTCTTGTGTTGGC CCCCACCAGGGTTGTTCTTTCTGAAATGAAGGAGGCTTTTCACGGCCTGGACGTGAAATTCCACACACAG GCTTTTTCCGCTCACGGCAGCGGGAGAGAAGTCATTGATGCCATGTGCCATGCCACCCTAACTTACAGGA TGTTGGAACCAACTAGGGTTGTTAACTGGGAAGTGATCATTATGGATGAAGCCCATTTTTTGGATCCAGC TAGCATAGCCGCTAGAGGTTGGGCAGCGCACAGAGCTAGGGCAAATGAAAGTGCAACAATCTTGATGACA GCCACACCGCCTGGGACTAGTGATGAATTTCCACATTCAAATGGTGAAATAGAAGATGTTCAAACGGACA TACCCAGTGAGCCCTGGAACACAGGGCATGACTGGATCCTAGCTGACAAAAGGCCCACGGCATGGTTCCT TCCATCCATCAGAGCTGCAAATGTCATGGCTGCCTCTTTGCGTAAGGCTGGAAAGAGTGTGGTGGTCCTG AACAGGAAAACCTTTGAGAGAGAATACCCCACGATAAAGCAGAAGAAACCTGACTTTATATTGGCCACTG ACATAGCTGAAATGGGAGCCAACCTTTGCGTGGAGCGAGTGCTGGATTGCAGGACGGCTTTTAAGCCTGT GCTTGTGGATGAAGGGAGGAAGGTGGCAATAAAAGGGCCACTTCGTATCTCCGCATCCTCTGCTGCTCAA AGGAGGGGGCGCATTGGGAGAAATCCCAACAGAGATGGAGACTCATACTACTATTCTGAGCCTACAAGTG AAAATAATGCCCACCACGTCTGCTGGTTGGAGGCCTCAATGCTCTTGGACAACATGGAGGTGAGGGGTGG AATGGTCGCCCCACTCTATGGCGTTGAAGGAACTAAAACACCAGTTTCCCCTGGTGAAATGAGACTGAGG GATGACCAGAGGAAAGTCTTCAGAGAACTAGTGAGGAATTGTGACCTGCCCGTTTGGCTTTCGTGGCAAG TGGCCAAGGCTGGTTTGAAGACGAATGATCGTAAGTGGTGTTTTGAAGGCCCTGAGGAACATGAGATCTT GAATGACAGCGGTGAAACAGTGAAGTGCAGGGCTCCTGGAGGAGCAAAGAAGCCTCTGCGCCCAAGGTGG TGTGATGAAAGGGTGTCATCTGACCAGAGTGCGCTGTCTGAATTTATTAAGTTTGCTGAAGGTAGGAGGG GAGCTGCTGAAGTGCTAGTTGTGCTGAGTGAACTCCCTGATTTCCTGGCTAAAAAAGGTGGAGAGGCAAT GGATACCATCAGTGTGTTCCTCCACTCTGAGGAAGGCTCTAGGGCTTACCGCAATGCACTATCAATGATG CCTGAGGCAATGACAATAGTCATGCTGTTTATACTGGCTGGACTACTGACATCGGGAATGGTCATCTTTT TCATGTCTCCCAAAGGCATCAGTAGAATGTCTATGGCGATGGGCACAATGGCCGGCTGTGGATATCTCAT GTTCCTTGGAGGCGTCAAACCCACTCACATCTCCTATGTCATGCTCATATTCTTTGTCCTGATGGTGGTT GTGATCCCCGAGCCAGGGCAACAAAGGTCCATCCAAGACAACCAAGTGGCATACCTCATTATTGGCATCC TGACGCTGGTTTCAGCGGTGGCAGCCAACGAGCTAGGCATGCTGGAGAAAACCAAAGAGGACCTCTTTGG GAAGAAGAACTTAATTCCATCTAGTGCTTCACCCTGGAGTTGGCCGGATCTTGACCTGAAGCCAGGAGCT GCCTGGACAGTGTACGTTGGCATTGTTACAATGCTCTCTCCAATGTTGCACCACTGGATCAAAGTCGAAT ATGGCAACCTGTCTCTGTCTGGAATAGCCCAGTCAGCCTCAGTCCTTTCTTTCATGGACAAGGGGATACC ATTCATGAAGATGAATATCTCGGTCATAATGCTGCTGGTCAGTGGCTGGAATTCAATAACAGTGATGCCT CTGCTCTGTGGCATAGGGTGCGCCATGCTCCACTGGTCTCTCATTTTACCTGGAATCAAAGCGCAGCAGT CAAAGCTTGCACAGAGAAGGGTGTTCCATGGCGTTGCCGAGAACCCTGTGGTTGATGGGAATCCAACAGT TGACATTGAGGAAGCTCCTGAAATGCCTGCCCTTTATGAGAAGAAACTGGCTCTATATCTCCTTCTTGCT CTCAGCCTAGCTTCTGTTGCCATGTGCAGAACGCCCTTTTCATTGGCTGAAGGCATTGTCCTAGCATCAG CTGCCTTAGGGCCGCTCATAGAGGGAAACACCAGCCTTCTTTGGAATGGACCCATGGCTGTCTCCATGAC AGGAGTCATGAGGGGGAATCACTATGCTTTTGTGGGAGTCATGTACAATCTATGGAAGATGAAAACTGGA CGCCGGGGGAGCGCGAATGGAAAAACTTTGGGTGAAGTCTGGAAGAGGGAACTGAATCTGTTGGACAAGC GACAGTTTGAGTTGTATAAAAGGACCGACATTGTGGAGGTGGATCGTGATACGGCACGCAGGCATTTGGC CGAAGGGAAGGTGGACACCGGGGTGGCGGTCTCCAGGGGGACCGCAAAGTTAAGGTGGTTCCATGAGCGT GGCTATGTCAAGCTGGAAGGTAGGGTGATTGACCTGGGGTGTGGCCGCGGAGGCTGGTGTTACTACGCTG CTGCGCAAAAGGAAGTGAGTGGGGTCAAAGGATTTACTCTTGGAAGAGACGGCCATGAGAAACCCATGAA TGTGCAAAGTCTGGGATGGAACATCATCACCTTCAAGGACAAAACTGATATCCACCGCCTAGAACCAGTG AAATGTGACACCCTTTTGTGTGACATTGGAGAGTCATCATCGTCATCGGTCACAGAGGGGGAAAGGACCG TGAGAGTTCTTGATACTGTAGAAAAATGGCTGGCTTGTGGGGTTGACAACTTCTGTGTGAAGGTGTTAGC TCCATACATGCCAGATGTTCTCGAGAAACTGGAATTGCTCCAAAGGAGGTTTGGCGGAACAGTGATCAGG AACCCTCTCTCCAGGAATTCCACTCATGAAATGTACTACGTGTCTGGAGCCCGCAGCAATGTCACATTTA CTGTGAACCAAACATCCCGCCTCCTGATGAGGAGAATGAGGCGTCCAACTGGAAAAGTGACCCTGGAGGC TGACGTCATCCTCCCAATTGGGACACGCAGTGTTGAGACAGACAAGGGACCCCTGGACAAAGAGGCCATA GAAGAAAGGGTTGAGAGGATAAAATCTGAGTACATGACCTCTTGGTTTTATGACAATGACAACCCCTACA GGACCTGGCACTACTGTGGCTCCTATGTCACAAAAACCTCAGGAAGTGCGGCGAGCATGGTAAATGGTGT TATTAAAATTCTGACATATCCATGGGACAGGATAGAGGAGGTCACAAGAATGGCAATGACTGACACAACC CCTTTTGGACAGCAAAGAGTGTTTAAAGAAAAAGTTGACACCAGAGCAAAGGATCCACCAGCGGGAACTA GGAAGATCATGAAAGTTGTCAACAGGTGGCTGTTCCGCCACCTGGCCAGAGAAAAGAACCCCAGACTGTG CACAAAGGAAGAATTTATTGCAAAAGTCCGAAGTCATGCAGCCATTGGAGCTTACCTGGAAGAACAAGAA CAGTGGAAGACTGCCAATGAGGCTGTCCAAGACCCAAAGTTCTGGGAACTGGTGGATGAAGAAAGGAAGC TGCACCAACAAGGCAGGTGTCGGACTTGTGTGTACAACATGATGGGGAAAAGAGAGAAGAAGCTGTCAGA GTTTGGGAAAGCAAAGGGAAGCCGTGCCATATGGTATATGTGGCTGGGAGCGCGGTATCTTGAGTTTGAG GCCCTGGGATTCCTGAATGAGGACCATTGGGCTTCCAGGGAAAACTCAGGAGGAGGAGTGGAAGGCATTG GCTTACAATACCTAGGATATGTGATCAGAGACCTGGCTGCAATGGATGGTGGTGGATTCTACGCGGATGA CACCGCTGGATGGGACACGCGCATCACAGAGGCAGACCTTGATGATGAACAGGAGATCTTGAACTACATG AGCCCACATCACAAAAAACTGGCACAAGCAGTGATGGAAATGACATACAAGAACAAAGTGGTGAAAGTGT TGAGACCAGCCCCAGGAGGGAAAGCCTACATGGATGTCATAAGTCGACGAGACCAGAGAGGATCCGGGCA GGTAGTGACTTATGCTCTGAACACCATCACCAACTTGAAAGTCCAATTGATCAGAATGGCAGAAGCAGAG ATGGTGATACATCACCAACATGTTCAAGATTGTGATGAATCAGTTCTGACCAGGCTGGAGGCATGGCTCA CTGAGCACGGATGTGACAGACTGAAGAGGATGGCGGTGAGTGGAGACGACTGTGTGGTCCGGCCCATCGA TGACAGGTTCGGCCTGGCCCTGTCCCATCTCAACGCCATGTCCAAGGTTAGAAAGGACATATCTGAATGG CAGCCATCAAAAGGGTGGAATGATTGGGAGAATGTGCCCTTCTGTTCCCACCACTTCCATGAACTACAGC TGAAGGATGGCAGGAGGATTGTGGTGCCTTGCCGAGAACAGGACGAGCTCATTGGGAGAGGAAGGGTGTC TCCAGGAAACGGCTGGATGATCAAGGAAACAGCTTGCCTCAGCAAAGCCTATGCCAACATGTGGTCACTG ATGTATTTTCACAAAAGGGACATGAGGCTACTGTCATTGGCTGTTTCCTCAGCTGTTCCCACCTCATGGG TTCCACAAGGACGCACAACATGGTCGATTCATGGGAAAGGGGAGTGGATGACCACGGAAGACATGCTTGA GGTGTGGAACAGAGTATGGATAACCAACAACCCACACATGCAGGACAAGACAATGGTGAAAAAATGGAGA GATGTCCCTTATCTAACCAAGAGACAAGACAAGCTGTGCGGATCACTGATTGGAATGACCAATAGGGCCA CCTGGGCCTCCCACATCCATTTAGTCATCCATCGTATCCGAACGCTGATTGGACAGGAGAAATACACTGA CTACCTAACAGTCATGGACAGGTATTCTGTGGATGCTGACCTGCAACTGGGTGAGCTTATCTGAAACACC ATCTAACAGGAATAACCGGGATACAAACCACGGGTGGAGAACCGGACTCCCCACAACCTGAAACCGGGAT ATAAACCACGGCTGGAGAACCGGGCTCCGCACTTAAAATGAAACAGAAACCGGGATAAAAACTACGGATG GAGAACCGGACTCCACACATTGAGACAGAAGAAGTTGTCAGCCCAGAACCCCACACGAGTTTTGCCACTG CTAAGCTGTGAGGCAGTGCAGGCTGGGACAGCCGACCTCCAGGTTGCGAAAAACCTGGTTTCTGGGACCT CCCACCCCAGAGTAAAAAGAACGGAGCCTCCGCTACCACCCTCCCACGTGGTGGTAGAAAGACGGGGTCT AGAGGTTAGAGGAGACCCTCCAGGGAACAAATAGTGGGACCATATTGACGCCAGGGAAAGACCGGAGTGG TTCTCTGCTTTTCCTCCAGAGGTCTGTGAGCACAGTTTGCTCAAGAATAAGCAGACCTTTGGATGACAAA CACAAAACCAC >NP_041726.1 polyprotein precursor [Yellow fever virus] MSGRKAQGKTLGVNMVRRGVRSLSNKIKQKTKQIGNRPGPSRGVQGFIFFFLFNILTGKKITAHLKRLWK MLDPRQGLAVLRKVKRVVASLMRGLSSRKRRSHDVLTVQFLILGMLLMTGGVTLVRKNRWLLLNVTSEDL GKTFSVGTGNCTTNILEAKYWCPDSMEYNCPNLSPREEPDDIDCWCYGVENVRVAYGKCDSAGRSRRSRR AIDLPTHENHGLKTRQEKWMTGRMGERQLQKIERWFVRNPFFAVTALTIAYLVGSNMTQRVVIALLVLAV GPAYSAHCIGITDRDFIEGVHGGTWVSATLEQDKCVTVMAPDKPSLDISLETVAIDRPAEVRKVCYNAVL THVKINDKCPSTGEAHLAEENEGDNACKRTYSDRGWGNGCGLFGKGSIVACAKFTCAKSMSLFEVDQTKI QYVIRAQLHVGAKQENWNTDIKTLKFDALSGSQEVEFIGYGKATLECQVQTAVDFGNSYIAEMETESWIV DRQWAQDLTLPWQSGSGGVWREMHHLVEFEPPHAATIRVLALGNQEGSLKTALTGAMRVTKDTNDNNLYK LHGGHVSCRVKLSALTLKGTSYKICTDKMFFVKNPTDTGHGTVVMQVKVSKGAPCRIPVIVADDLTAAIN KGILVTVNPIASTNDDEVLIEVNPPFGDSYIIVGRGDSRLTYQWHKEGSSIGKLFTQTMKGVERLAVMGD TAWDFSSAGGFFTSVGKGIHTVFGSAFQGLFGGLNWITKVIMGAVLIWVGINTRNMTMSMSMILVGVIMM FLSLGVGADQGCAINFGKRELKCGDGIFIFRDSDDWLNKYSYYPEDPVKLASIVKASFEEGKCGLNSVDS LEHEMWRSRADEINAIFEENEVDISVVVQDPKNVYQRGTHPFSRIRDGLQYGWKTWGKNLVFSPGRKNGS FIIDGKSRKECPFSNRVWNSFQIEEFGTGVFTTRVYMDAVFEYTIDCDGSILGAAVNGKKSAHGSPTFWM GSHEVNGTWMIHTLEALDYKECEWPLTHTIGTSVEESEMFMPRSIGGPVSSHNHIPGYKVQTNGPWMQVP LEVKREACPGTSVIIDGNCDGRGKSTRSTTDSGKVIPEWCCRSCTMPPVSFHGSDGCWYPMEIRPRKTHE SHLVRSWVTAGEIHAVPFGLVSMMIAMEVVLRKRQGPKQMLVGGVVLLGAMLVGQVTLLDLLKLTVAVGL HFHEMNNGGDAMYMALIAAFSIRPGLLIGFGLRTLWSPRERLVLTLGAAMVEIALGGVMGGLWKYLNAVS LCILTINAVASRKASNTILPLMALLTPVTMAEVRLAAMFFCAVVIIGVLHQNFKDTSMQKTIPLVALTLT SYLGLTQPFLGLCAFLATRIFGRRSIPVNEALAAAGLVGVLAGLAFQEMENFLGPIAVGGLLMMLVSVAG RVDGLELKKLGEVSWEEEAEISGSSARYDVALSEQGEFKLLSEEKVPWDQVVMTSLALVGAALHPFALLL VLAGWLFHVRGARRSGDVLWDIPTPKIIEECEHLEDGIYGIFQSTFLGASQRGVGVAQGGVFHTMWHVTR GAFLVRNGKKLIPSWASVKEDLVAYGGSWKLEGRWDGEEEVQLIAAVPGKNVVNVQTKPSLFKVRNGGEI GAVALDYPSGTSGSPIVNRNGEVIGLYGNGILVGDNSFVSAISQTEVKEEGKEELQEIPTMLKKGMTTVL DFHPGAGKTRRFLPQILAECARRRLRTLVLAPTRVVLSEMKEAFHGLDVKFHTQAFSAHGSGREVIDAMC HATLTYRMLEPTRVVNWEVIIMDEAHFLDPASIAARGWAAHRARANESATILMTATPPGTSDEFPHSNGE IEDVQTDIPSEPWNTGHDWILADKRPTAWFLPSIRAANVMAASLRKAGKSVVVLNRKTFEREYPTIKQKK PDFILATDIAEMGANLCVERVLDCRTAFKPVLVDEGRKVAIKGPLRISASSAAQRRGRIGRNPNRDGDSY YYSEPTSENNAHHVCWLEASMLLDNMEVRGGMVAPLYGVEGTKTPVSPGEMRLRDDQRKVFRELVRNCDL PVWLSWQVAKAGLKTNDRKWCFEGPEEHEILNDSGETVKCRAPGGAKKPLRPRWCDERVSSDQSALSEFI KFAEGRRGAAEVLVVLSELPDFLAKKGGEAMDTISVFLHSEEGSRAYRNALSMMPEAMTIVMLFILAGLL TSGMVIFFMSPKGISRMSMAMGTMAGCGYLMFLGGVKPTHISYVMLIFFVLMVVVIPEPGQQRSIQDNQV AYLIIGILTLVSAVAANELGMLEKTKEDLFGKKNLIPSSASPWSWPDLDLKPGAAWTVYVGIVTMLSPML HHWIKVEYGNLSLSGIAQSASVLSFMDKGIPFMKMNISVIMLLVSGWNSITVMPLLCGIGCAMLHWSLIL PGIKAQQSKLAQRRVFHGVAENPVVDGNPTVDIEEAPEMPALYEKKLALYLLLALSLASVAMCRTPFSLA EGIVLASAALGPLIEGNTSLLWNGPMAVSMTGVMRGNHYAFVGVMYNLWKMKTGRRGSANGKTLGEVWKR ELNLLDKRQFELYKRTDIVEVDRDTARRHLAEGKVDTGVAVSRGTAKLRWFHERGYVKLEGRVIDLGCGR GGWCYYAAAQKEVSGVKGFTLGRDGHEKPMNVQSLGWNIITFKDKTDIHRLEPVKCDTLLCDIGESSSSS VTEGERTVRVLDTVEKWLACGVDNFCVKVLAPYMPDVLEKLELLQRRFGGTVIRNPLSRNSTHEMYYVSG ARSNVTFTVNQTSRLLMRRMRRPTGKVTLEADVILPIGTRSVETDKGPLDKEAIEERVERIKSEYMTSWF YDNDNPYRTWHYCGSYVTKTSGSAASMVNGVIKILTYPWDRIEEVTRMAMTDTTPFGQQRVFKEKVDTRA KDPPAGTRKIMKVVNRWLFRHLAREKNPRLCTKEEFIAKVRSHAAIGAYLEEQEQWKTANEAVQDPKFWE LVDEERKLHQQGRCRTCVYNMMGKREKKLSEFGKAKGSRAIWYMWLGARYLEFEALGFLNEDHWASRENS GGGVEGIGLQYLGYVIRDLAAMDGGGFYADDTAGWDTRITEADLDDEQEILNYMSPHHKKLAQAVMEMTY KNKVVKVLRPAPGGKAYMDVISRRDQRGSGQVVTYALNTITNLKVQLIRMAEAEMVIHHQHVQDCDESVL TRLEAWLTEHGCDRLKRMAVSGDDCVVRPIDDRFGLALSHLNAMSKVRKDISEWQPSKGWNDWENVPFCS HHFHELQLKDGRRIVVPCREQDELIGRGRVSPGNGWMIKETACLSKAYANMWSLMYFHKRDMRLLSLAVS SAVPTSWVPQGRTTWSIHGKGEWMTTEDMLEVWNRVWITNNPHMQDKTMVKKWRDVPYLTKRQDKLCGSL IGMTNRATWASHIHLVIHRIRTLIGQEKYTDYLTVMDRYSVDADLQLGELI Protective antigen prM from Dengue virus 1 Dengue virus 1 18308046 CDD:279856 CDD:279358 11053 ? premembrane 5.16 11796.33 161 Flavivirus polyprotein propeptide; pfam01570 >AAL67809.1 premembrane, partial [Dengue virus 1] FHLTTRGGEPHMIVSKQERGKSLLFKTSAGVNMCTLIAMDLGELCEDTMTYKCPRITEAEPDDVDCWCNA TDTWVTYGTCSQTGEHRRDKRSVALAPHVGLGLETRTE Protective antigen prM from Dengue virus 2 Dengue virus 2 18308058 CDD:279856 CDD:279358 11060 ? premembrane 6.34 13464.2 172 Flavivirus polyprotein propeptide; pfam01570 >AAL67815.1 premembrane, partial [Dengue virus 2] FHLTTRNGEPHMIVSRQEKGKSLLFKTKDGTNMCTLMAMDLGELCEDTITYKCPFLKQNEPEDIDCWCNS TSTWVTYGTCTTTGEHRREKRSVALVPHVGMGLETRTETWMSSEGAWKH Protective antigen prM from Dengue virus 3 Dengue virus 3 18308070 CDD:279856 CDD:279358 11069 ? premembrane 5.57 12139.72 163 Flavivirus polyprotein propeptide; pfam01570 >AAL67821.1 premembrane, partial [Dengue virus 3] FHLTSRDGEPRMIVGKNERGKSLLFKTASGINMCTLIAMDLGEMCDDTVTYKCPHITEVEPEDIDCWCNL TSTWVTYGTCNQAGEHRRDKRSVALAPHVGMGLDTRTQTW Protective antigen prM from Dengue virus 4 VO_0011315 18308086 CDD:279856 CDD:279358 11070 ? premembrane 184 Flavivirus polyprotein propeptide; pfam01570 >AAL67829.1 premembrane, partial [Dengue virus 4] FHLSTRDGEPLMIVAKHERGRPLLFKTTEGINKCTLIAMDLGEMCEDTVTYKCPLLVNTEPEDIDCWCNL TSTWVMYGTCPQSGERRREKRSVALTPHSGMGLETRAETWMSSEGAWKHAQRVESWILRNP Protective antigen A recombinant vaccinia virus that expressed the pre-M protein of Dengue 4 virus was constructed. Mice immunized with the recombinant virus were protected against subsequent dengue 4 encephalitis challenge [Ref1376:Bray and Lai, 1991]. 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