Database of articles cited by EMDB/PDB/SASBDB data

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Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
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IF	>30 >20 >10 >5 all

Title	Ultrapotent Broadly Neutralizing Human-llama Bispecific Antibodies against HIV-1.
Journal, issue, pages	Adv Sci (Weinh), Vol. 11, Issue 26, Page e2309268, Year 2024
Publish date	May 5, 2024
Authors	Jianliang Xu / Tongqing Zhou / Krisha McKee / Baoshan Zhang / Cuiping Liu / Alexandra F Nazzari / Amarendra Pegu / Chen-Hsiang Shen / Jordan E Becker / Michael F Bender / Payton Chan / Anita Changela / Ridhi Chaudhary / Xuejun Chen / Tal Einav / Young Do Kwon / Bob C Lin / Mark K Louder / Jonah S Merriam / Nicholas C Morano / Sijy O'Dell / Adam S Olia / Reda Rawi / Ryan S Roark / Tyler Stephens / I-Ting Teng / Emily Tourtellott-Fogt / Shuishu Wang / Eun Sung Yang / Lawrence Shapiro / Yaroslav Tsybovsky / Nicole A Doria-Rose / Rafael Casellas / Peter D Kwong /
PubMed Abstract	Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a ...Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV-1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion-stabilized HIV-1 envelope (Env) trimer, BG505 DS-SOSIP, and the identification and improvement of potent neutralizing nanobodies recognizing the CD4-binding site (CD4bs) of vulnerability. Two of the vaccine-elicited CD4bs-targeting nanobodies, G36 and R27, when engineered into a triple tandem format with llama IgG2a-hinge region and human IgG1-constant region (G36×3-IgG2a and R27×3-IgG2a), neutralized 96% of a multiclade 208-strain panel at geometric mean ICs of 0.314 and 0.033 µg mL, respectively. Cryo-EM structures of these nanobodies in complex with Env trimer revealed the two nanobodies to neutralize HIV-1 by mimicking the recognition of the CD4 receptor. To enhance their neutralizing potency and breadth, nanobodies are linked to the light chain of the V2-apex-targeting broadly neutralizing antibody, CAP256V2LS. The resultant human-llama bispecific antibody CAP256L-R27×3LS exhibited ultrapotent neutralization and breadth exceeding other published HIV-1 broadly neutralizing antibodies, with pharmacokinetics determined in FcRn-Fc mice similar to the parent CAP256V2LS. Vaccine-elicited llama nanobodies, when combined with V2-apex broadly neutralizing antibodies, may therefore be able to fulfill anti-HIV-1 therapeutic and prophylactic clinical goals.
External links	Adv Sci (Weinh) / PubMed:38704686 / PubMed Central
Methods	EM (single particle)
Resolution	3.32 - 3.61 Å
Structure data	41415 8tng EMDB-41415, PDB-8tng: Cryo-EM structure of HIV-1 Env BG505 DS-SOSIP in complex with broadly neutralizing llama nanobody R27 targeting the CD4-binding site Method: EM (single particle) / Resolution: 3.58 Å 41416 8tnh EMDB-41416, PDB-8tnh: Cryo-EM structure of HIV-1 Env BG505 DS-SOSIP in complex with broadly neutralizing llama nanobody G36 targeting the CD4-binding site Method: EM (single particle) / Resolution: 3.32 Å 41417 8tni EMDB-41417, PDB-8tni: Cryo-EM structure of HIV-1 Env BG505 DS-SOSIP in complex with broadly neutralizing bi-specific antibody CAP256L-R27 targeting the CD4-binding site and the V2-apex Method: EM (single particle) / Resolution: 3.61 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose
Source	lama glama (llama) human immunodeficiency virus 1 homo sapiens (human)
Keywords	VIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 Envelope / antibody / nanobody / VHH / llama / BG505 DS-SOSIP / neutralization / immunization / VIRAL PROTEIN-IMMUNE SYSTEM complex / bi-specific / CAP256 / R27