IP Library › Granted Patent US 12,415,836
Granted Patent B2
US 12,415,836 · App. 17/510,930 · Granted Sep 16, 2025

Anti-dengue vaccines and antibodies

Inventors: Gavin Screaton (London, GB); Juthathip Mongkolsapaya (London, GB); Alexander Rouvinski (Paris, FR); Pablo Guardado-Calvo (Paris, FR); Giovanna Barba-Spaeth (Paris, FR); Stéphane Duquerroy (Paris, FR); Marie-Christine Vaney (Paris, FR); Felix Augusto Rey (Paris, FR)
Assignees: OXFORD UNIVERSITY INNOVATION LIMITED; Universite Paris-Saclay
C07K14/005A61K39/12A61K47/6841C07K14/1825C07K16/1081A61K2039/5258A61K2039/545C07K2317/21C07K2317/33C07K2317/34C07K2317/56C07K2317/76C12N2770/24122C12N2770/24134Y02A50/30
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,415,836
App. No.
17/510,930
Granted
Sep 16, 2025
Kind
B2
Abstract

A Dengue virus Envelope Dimer Epitope (EDE) wherein the EDE: c) spans the polypeptides of a Dengue virus Envelope polypeptide dimer; and/or d) is presented on a dimer of Envelope proteins; and/or c) is formed from consecutive or nonconsecutive residues of the envelope polypeptide dimer, wherein the dimer is a homodimer or heterodimer of native and/or mutant envelope polypeptides, from any one or two of DENV-1, DENV-2, DENV-3 and DENV-4. The EDE may be a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, wherein the dimer is: covalently stabilized with at least one disulphide inter-chain bond between the two sE monomers, and/or covalently stabilized with at least one sulfhydryl-reactive crosslinker between the two sE monomers, and/or covalently stabilized by linking the two sE monomers through modified sugars; and/or, covalently stabilised by being formed as a single polypeptide chain, optionally with a linker region, optionally a Glycine Serine rich linker region, separating the sE sequences, and/or non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid, at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer. A compound, for example an antibody or antibody fragment that can neutralise more than one Dengue virus serotype, for example an antibody that can bind to an EDE of the invention.

Claims (59)

1. A composition comprising an adjuvant and a compound that binds to an E-Dimer Epitope (EDE), wherein the compound is an antibody comprising a heavy chain comprising CDR regions and light chain comprising CDR regions, or antigen binding portion thereof,

wherein the antibody, or antigen binding portion thereof, comprises:

a) a heavy chain variable region comprising the amino acid sequences SEQ ID NO: 5, 6 and 7 and a light chain variable region comprising the amino acid sequences SEQ ID NO: 17, 18 and 19; or

b) a heavy chain variable region comprising the amino acid sequences SEQ ID NO: 8, 9 and 10 and a light chain variable region comprising the amino acid sequences SEQ ID NO: 20, 21 and 22; or

c) a heavy chain variable region comprising the amino acid sequences SEQ ID NO: 11, 12 and 13 and a light chain variable region comprising the amino acid sequences SEQ ID NO: 23, 24 and 25; or

d) a heavy chain variable region comprising the amino acid sequences SEQ ID NO: 14, 15, and 16 and a light chain variable region comprising the amino acid sequences SEQ ID NO: 26, 27 and 28;

wherein the EDE comprises a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, a dimer of Envelope proteins, or the antigenic portion thereof, or consecutive or non-consecutive residues of the envelope polypeptide dimer, held within a heterologous scaffold protein, and

wherein said antibody or fragment thereof binds the five polypeptide segments of the dengue virus glycoprotein E ectodomain consisting of the residues 67-74, residues 97-106, residues 307-314, residues 148-159 and residues 243-251, wherein the amino acid residue position of each sE monomer is numbered according to SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135.

2. The composition according to claim 1 , wherein the stabilised EDE is any one or more of:

a) a dimer wherein the monomer is selected from the group consisting of: the DENV-1 sE of SEQ ID NO: 132, the DENV-2 SE of SEQ ID NO: 133 the DENV-3 SE of SEQ ID NO: 134, the DENV-4 sE of SEQ ID NO: 135 and a mutant sE thereof having at least one mutation selected among H27F, H27W, L107C, F108C, H244F, H244W, S255C, A259C, T/S262C, T/A265C, L278F, L292F, L294N, A313C and T315C and optionally at least one additional mutation selected from the group consisting of Q227N, E174N and D329N;

b) a homodimer of two identical recombinant sE or a heterodimer of two different recombinant sE;

c) a dimer which is glycosylated at position 67, at position 153 of each sE monomer, or both;

d) a dimer which is covalently stabilized with at least one, two or three disulphide inter-chain bonds between the two sE monomers;

e) a homodimer of mutant sE having each the mutation A259C or S255C and wherein the residues 259C or 255C are linked together through a disulphide inter-chain bond;

f) a dimer which is a heterodimer of a mutant sE having the mutation A259C and a mutant sE having the mutation S255C, wherein the residues 259C and 255C are linked together through a disulphide inter-chain bond;

g a homodimer of mutant sE having each the mutations F108C and T315C or a homodimer of mutants sE having each the mutations L107C and A313C wherein the residues 108C and 315C or the residues 107C and 313C are linked together through a disulphide inter-chain bond;

h) a heterodimer of a mutant sE having the mutations F108C and A313C and a mutant sE having the mutations L107C and T315C wherein the residues 108C and 313C are linked respectively to the residues 315C and 107C through a disulphide inter-chain bond between the two sE monomers;

i) a dimer, selected from the group consisting of a homodimer of mutants sE having each the mutations A259C, F108C and T315C, a homodimer of mutants sE having each the mutations S255C, F108C and T315C, a homodimer of mutants sE having each the mutations A259C, L107C and A313C, and a homodimer of mutants sE having each the mutations A255C, L107C and A313C as defined above, wherein the residues 259C, 255C, 108C, 315C, 107C and 313C are linked respectively to the residues 259C, 255C, 315C, 108C, 313C and 107C through disulphide inter-chain bonds;

j) a heterodimer of a mutant sE having the mutations A259C, F108C and T315C and a mutant sE having the mutations S255C, F108C and T315C as defined above, wherein the residues 259C, 108C and 315C are linked respectively to the residues 255C, 315C and 108C through disulphide inter-chain bonds;

k) a heterodimer of a mutant sE having the mutations S255C, L107C and A313C and a mutant sE having the mutations A259C, L107C and A313C, wherein the residues 255C, 107C and 313C are linked respectively to the residues 259C, 313C and 107C through disulphide inter-chain bonds;

l) a dimer which is covalently stabilized with at least one, two or three, sulfhydryl-reactive crosslinkers (also called thiol-reactive crosslinkers) between the sE monomers;

m) is a homodimer of mutant sE having each the mutation T/S262C or T/A265C, wherein the residues 262C or 265C are linked together through a sulfhydryl-reactive crosslinker;

n) a heterodimer of a mutant sE having the mutation T/S262C as defined above and a mutant sE having the mutation T/A265C, wherein the residues 262C and 265C are linked together through a sulfhydryl-reactive crosslinker;

o) a homodimer or a heterodimer of a mutant sE wherein at least one of the amino acid residues 1-9, 25-30, 238-282, 96-111 311-318 of sE is mutated to cysteine and a mutant sE wherein at least one of the amino acid residues 1-9, 25-30, 238-282, 96-111 311-318 of sE is mutated to cysteine, and wherein the mutated cysteine residues are linked together through a sulfhydryl-reactive crosslinker;

p) a dimer which is covalently stabilized by linking the two monomers through modified sugars;

q) a homodimer or heterodimer of mutant sE, wherein:

one sE monomer has at least one mutation which introduces a glycosylation site, and wherein the mutated amino acid residue is glycosylated with a modified sugar bearing an X functional group, and the other sE monomer has at least one mutation which introduces a glycosylation site, and wherein the mutated amino acid residue is glycosylated with a modified sugar bearing a Y functional group, and wherein both mutated residues are joined together through the modified sugars by reacting, specifically by click chemistry, the X functional group of the sugar of the first sE monomer with the Y functional group of the sugar of the other sE monomer;

r) a dimer which is non-covalently stabilized by filling the cavities of said dimer at the dimer interface by substituting at least one amino acid in the amino acid sequence of one or the two monomers, with bulky side chain amino acids;

s) a dimer which is non-covalently stabilized by substituting at least one amino acid residue in the amino acid sequence of at least one sE monomer with at least one bulky side chain amino acid within regions forming cavities at the dimer interface or in domain 1 (D1)/domain 3 (D3) linker of each monomer increasing hydrophobic interactions between the two sE monomers;

t) a homodimer or heterodimer of two recombinant sE as defined above, wherein one of the recombinant sE or the two recombinant sE have at least one mutation selected from the group consisting of H27F, H27W, H244F, H244W, and L278F;

u) a dimer which is non-covalently stabilized in domain 1 (D1)/domain 3 (D3) linker of each monomer, by substituting amino acids in the amino acid sequence of one or the two monomers with at least one bulky side chain amino acid;

v) a dimer which is a homodimer or heterodimer of two recombinant sE as defined above, wherein one of the recombinant sE or the two recombinant sE have at least one mutation selected from the group consisting of L292F and L294N,

wherein the amino acid residue position of each sE monomer is numbered according to SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135.

3. The composition according to claim 1 wherein the compound does not bind:

a) only to the fusion loop; or

b) to the Envelope protein when in a denatured form; or

c) made in cells lacking furin activity, and/or at low pH.

4. The composition according to claim 1 wherein the compound neutralises one or more serotypes of Dengue virus to 80% or 90% or 98% or 100%.

5. The composition according to claim 1 , wherein the compound neutralises one or more serotypes of Dengue virus to 80% or 90% or 100% at a concentration of 0.5 μg/ml.

6. The composition according to claim 1 wherein the compound neutralises virus made in C6/36 insect cells and human dendritic cells to the same level.

7. The composition according to claim 1 wherein the compound is conjugated to a further agent, optionally wherein the further agent is a therapeutic agent, optionally an anti-viral agent; or wherein the further agent is a stabilising agent, optionally PEG.

8. The composition according to claim 1 , wherein the antibody, or antigen binding portion thereof, comprises:

a) heavy chain comprising SEQ ID NO: 1 and the light chain comprising SEQ ID NO: 37; or

b) heavy chain comprising SEQ ID NO: 2 and the light chain comprising SEQ ID NO: 38; or

c) heavy chain comprising SEQ ID NO: 3 and the light chain comprising SEQ ID NO: 39; or

d) heavy chain comprising SEQ ID NO: 4 and the light chain comprising SEQ ID NO: 40; or comprises a sequence with at least 90% homology to the said sequences.

9. The composition according to claim 2 wherein the mutant sE having at least one mutation selected among H27F, H27W, L107C, F108C, H244F, H244W, S255C, A259C, T/S262C, T/A265C, L278F, L292F, L294N, A313C and T315C comprises the three mutations Q227N, E174N and D329N, wherein the amino acid residue position of each sE monomer is numbered according to SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, and SEQ ID NO: 135.

10. The composition of claim 7 , wherein the compound is conjugated to a therapeutic agent, an anti-viral agent; or a stabilising agent.

11. The composition of claim 10 , wherein the stabilizing agent comprises PEG.

12. A composition comprising an adjuvant and a compound that binds to an E-Dimer Epitope (EDE), wherein the compound is an antibody, or an antigen binding portion thereof, comprising:

a) heavy chain comprising SEQ ID NO: 42 and the light chain comprising SEQ ID NO: 88; or

b) heavy chain comprising SEQ ID NO: 56 and the light chain comprising SEQ ID NO: 102; or

c) heavy chain comprising SEQ ID NO: 57 and the light chain comprising SEQ ID NO: 103; or

d) heavy chain comprising SEQ ID NO: 58 and the light chain comprising SEQ ID NO: 104; or

e) heavy chain comprising SEQ ID NO: 61 and the light chain comprising SEQ ID NO: 107; or

f) heavy chain comprising SEQ ID NO: 64 and the light chain comprising SEQ ID NO: 110; or

g) heavy chain comprising SEQ ID NO: 65 and the light chain comprising SEQ ID NO: 111; or

h) heavy chain comprising SEQ ID NO: 70 and the light chain comprising SEQ ID NO: 116;

wherein the EDE comprises a stabilized recombinant dengue virus envelope glycoprotein E ectodomain (sE) dimer, a dimer of Envelope proteins, or the antigenic portion thereof, or consecutive or non-consecutive residues of the envelope polypeptide dimer, held within a heterologous scaffold protein.

Assignments (9)
CORRECTIVE ASSIGNMENT TO CORRECT THE APPLICATION NUMBER PREVIOUSLY RECORDED AT REEL: 71593 FRAME: 14. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Sep 12, 2025
From: INSTITUT PASTEUR
To: OXFORD UNIVERSITY INNOVATION LIMITED
Reel/Frame 072877/0818 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 2, 2025
From: INSTITUT PASTEUR
To: OXFORD UNIVERSITY INNOVATION LIMITED
Reel/Frame 071593/0014 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 20, 2023
From: IMPERIAL COLLEGE INNOVATIONS LIMITED
To: INSTITUT PASTEUR
Reel/Frame 063387/0543 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2022
From: IMPERIAL INNOVATIONS LIMITED
To: IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
Reel/Frame 059036/0742 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2022
From: UNIVERSITY PARIS XI
To: UNIVERSITÉ PARIS-SACLAY
Reel/Frame 059037/0019 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2022
From: SCREATON, GAVIN; MONGKOLSAPAYA, JUTHATHIP
To: IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
Reel/Frame 059037/0120 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2022
From: IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
To: IMPERIAL COLLEGE INNOVATIONS LIMITED
Reel/Frame 059037/0250 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2022
From: ROUVINSKI, ALEXANDER; GUARDADO-CALVO, PABLO; BARBA-SPAETH, GIOVANNA; VANEY, MARIE-CHRISTINE; REY, FELIX
To: INSTITUT PASTEUR
Reel/Frame 059036/0018 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 17, 2022
From: DUQUERROY, STÉPHANE
To: UNIVERSITÉ PARIS-SUD
Reel/Frame 059036/0541 →
Priority Claims (1)
GB 1413086 · Jul 23, 2014 · national
Continuity (2)
Division 15328441
Related Publication 20220127307A1 · Apr 28, 2022
References Cited (88)
US 20030175304A1 · Peters · 2003 [cited by examiner]
US 20090311225A1 · Koduri · 2009 [cited by applicant]
US 20130316944A1 · Volkman · 2013 [cited by applicant]
WO 99006068 · 1999 [cited by applicant]
WO 2002077199 · 2002 [cited by applicant]
WO 2005003316 · 2005 [cited by applicant]
WO 2006033679 · 2006 [cited by applicant]
WO 2005056600 · 2006 [cited by applicant]
WO 2009098450 · 2009 [cited by applicant]
WO 2011050168 · 2011 [cited by applicant]
WO 2012154202 · 2012 [cited by applicant]
WO 2013151764 · 2013 [cited by applicant]
WO 2014074535 · 2014 [cited by applicant]
Allison, et al., “Oligomeric rearrangement of tick-borne encephalitis virus envelope proteins induced by an acidic pH”, [cited by applicant]
Allison, et al., “Mutational Evidence for an Internal Fusion Peptide in Flavivirus Envelope Protein E”, [cited by applicant]
Balakrishnan, et al., “Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection”, [cited by applicant]
Beltramello, et al., “The human immune response to Dengue virus is dominated by highly cross-reactive antibodies endowed with neutralizing and enhancing activity”, [cited by applicant]
Bommakanti, et al., “Design of an HA2-based [cited by applicant]
Bowie, et al., “Deciphering the Message in Protein Sequences: Tolerance to Amino Acid Substitutions”, [cited by applicant]
Bressanelli, et al., “Structure of a flavivirus envelope glycoprotein in its low-pH-induced membrane fusion conformation”, [cited by applicant]
Burton, “Scaffolding to build a rational vaccine design strategy”, [cited by applicant]
Cherrier, et al., “Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody”, [cited by applicant]
Cockburn, et al., “Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody”, [cited by applicant]
Cockburn, et al., “Structural insights into the neutralization mechanism of a higher primate antibody against dengue virus”, [cited by applicant]
Coller and Clements, “Dengue vaccines: progress and challenges”, [cited by applicant]
Costin, et al., “Mechanistic Study of Broadly Neutralizing Human Monoclonal Antibodies against Dengue Virus That Target the Fusion Loop”, [cited by applicant]
De Alwis, et al., “Identification of human neutralizing antibodies that bind to complex epitopes on dengue virions”, [cited by applicant]
Dejnirattisai, et al., “A complex interplay among virus, dendritic cells, T cells, and cytokines in dengue virus infections”, [cited by applicant]
Dejnirattisai, et al., “Corrigendum: A new class of highly potent, broadly neutralizing antibodies isolated from viremic patients infected with dengue virus”, [cited by applicant]
Dejnirattisai, et al., “Enhancing cross-reactive anti-prM dominates the human antibody response in dengue infection”, [cited by applicant]
Ekiert, et al., “A highly conserved neutralizing epitope on group 2 influenza A viruses”, [cited by applicant]
Fibriansah, et al., “Structural Changes in Dengue Virus When Exposed to a Temperature of 37C”, [cited by applicant]
Goncalvez, et al., “Epitope determinants of a chimpanzee Fab antibody that efficiently cross-neutralizes dengue type 1 and type 2 viruses map to inside and in close proximity to fusion loop of the dengue type 2 virus en… [cited by applicant]
Gromowski, et al., “Characterisation of Dengue virus complex-specific neutralizing epitopes on envelope protein domain III of dengue 2 virus”, [cited by applicant]
Halstead, “Neutralization and antibody-dependent enhancement of dengue viruses”, [cited by applicant]
Junjhon, et al., “Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles”, [cited by applicant]
Kabsch, “XDS”, [cited by applicant]
Kaufmann, et al., “Neutralization of West Nile virus by cross-linking of its surface proteins with Fab fragments of the human monoclonal antibody CR4354”, [cited by applicant]
Kuhn, et al., “Structure of dengue virus: implications for flavivirus organization, maturation, and fusion”, [cited by applicant]
Lai, et al., “Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of… [cited by applicant]
Lee, et al., “New vaccines against influenza virus”, [cited by applicant]
Li, et al., “Click Chemistry in Peptide-Based Drug Design”, [cited by applicant]
Li, et al., “The flavivirus precursor membrane-envelope protein complex: structure and maturation”, [cited by applicant]
Lin, et al., “Analysis of epitopes on dengue virus envelope protein recognized by monoclonal antibodies and polyclonal human sera by a high throughput assay”, [cited by applicant]
Lok, et al., “Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins”, [cited by applicant]
Mantel, et al., “Genetic stability of a dengue vaccine based on chimeric yellow fever/dengue viruses”, [cited by applicant]
Matsui, et al., “Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain III”, [cited by applicant]
McLellan, et al., “Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody”, [cited by applicant]
Modis, et al., “Structure of the dengue virus envelope protein after membrane fusion”, [cited by applicant]
Mongkolsapaya, et al., “Original antigenic sin and apoptosis in the pathogenesis of dengue hemorrhagic fever”, [cited by applicant]
Mukhopadhyay, et al., “A structural perspective of the flavivirus life cycle”, [cited by applicant]
Murphy and Whitehead, “Immune response to dengue virus and prospects for a vaccine”, [cited by applicant]
Nelson, et al., “Maturation of West Nile virus modulates sensitivity to antibody-mediated neutralization”, [cited by applicant]
Ofek, et al., “Elicitation of structure-specific antibodies by epitope scaffolds”, [cited by applicant]
Oliphant, et al., “Antibody recognition and neutralization determinants on domains I and II of West Nile Virus envelope protein”, [cited by applicant]
Osorio, et al., “Development of DENVax: A chimeric dengue-2 PDK-53-based tetravalent vaccine for protection against dengue fever”, [cited by applicant]
Plevka, et al., “Maturation of flaviviruses starts from one or more icosahedrally independent nucleation centres”, [cited by applicant]
Pokidysheva, et al., “Cryo-EM reconstruction of dengue virus in complex with the carbohydrate recognition domain of DC-SIGN”, [cited by applicant]
Punna, et al., “Head-to-Tail Peptide Cyclodimerization by Copper-Catalyzed zide-Alkyne Cycloaddition”, [cited by applicant]
Reeck, et al., ““Homology” in Proteins and Nucleic Acids: A Terminology Muddle and a Way out of It”, [cited by applicant]
Rey, “Two hosts, two structures”, [cited by applicant]
Rey, et al., “The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution”, [cited by applicant]
Rodenhuis-Zybert, et al., “A fusion-loop antibody enhances the infectious properties of immature flavivirus particles”, [cited by applicant]
Rodenhuis-Zybert, et al., “Immature dengue virus: a veiled pathogen”, [cited by applicant]
Rouvinski, et al., “Recognition determinants of broadly neutralizing human antibodies against dengue viruses”, [cited by applicant]
Sabchareon, et al., “Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial”, [cited by applicant]
Sasaki, et al., “Dengue virus neutralization and antibody-dependent enhancement activities of human monoclonal antibodies derived from dengue patients at acute phase of secondary infection”, [cited by applicant]
Simmons, et al. “Dengue”, [cited by applicant]
Sittisombut, et al., “Lack of augmenting effect of interferon-gamma on dengue virus multiplication in human peripheral blood monocytes”, [cited by applicant]
Smith, et al., “The potent and broadly neutralizing human dengue virus-specific monoclonal antibody 1C19 reveals a unique cross-reactive epitope on the bc loop of domain II of the envelope protein”, [cited by applicant]
Sukupolvi-Petty, et al., “Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2”, [cited by applicant]
Teoh, et al., “The structural basis for serotype-specific neutralization of Dengue virus by a human antibody”, [cited by applicant]
Thirumurugan, et al., “Click Chemistry for Drug Development and Diverse Chemical-Biology Applications”, [cited by applicant]
Tsai, et al., “High-avidity and potently neutralizing cross-reactive human monoclonal antibodies derived from secondary dengue virus infection”, [cited by applicant]
Wengler, et al., “The isolation of the ectodomain of the alphavirus E1 protein as a soluble hemagglutinin and its crystallization”, [cited by applicant]
Whittle, et al., “Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin”, [cited by applicant]
Wrammert, et al., “Rapid and massive virus-specific plasma blast responses during acute dengue virus infection in humans”, [cited by applicant]
Wu and Kabat, “An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for anti-body complementarity”, [cited by applicant]
Wu, et al., “Human skin Langerhans cells are targets of dengue virus infection”, [cited by applicant]
Yu, et al., “Structure of the immature dengue virus at low pH primes proteolytic maturation”, [cited by applicant]
Zhang, et al., “Conformational changes of the flavivirus E glycoprotein”, [cited by applicant]
Zhang, et al., “Cryo-EM structure of the mature dengue virus at 3.5-A resolution”, [cited by applicant]
Zhang, et al., “Dengue structure differs at the temperatures of its human and mosquito hosts”, [cited by applicant]
Zhou, et al., “Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01”, [cited by applicant]
Zhou, et al., “Structural definition of a conserved neutralization epitope on HIV1 gp120”, [cited by applicant]
Zidane, et al., “Cross-reactivities between human IgMs and the four serotypes of dengue virus as probed with artificial homodimers of domain-III from the envelope proteins”, [cited by applicant]
Allison, et al., “Mutational Evidence for an Internal Fusion Peptide in Flavivirus Envelope Proetin E”, J. of Virology, 4268-4275 (2001). [cited by applicant]
Zhang et al., “Molecular manipulation associated with disulphide bond formation to enhance the stability of recombinant therapeutic protein.” Protein Expression and Purification, 75:28-39(2011). [cited by applicant]