Database of articles cited by EMDB/PDB/SASBDB data

Keywords
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
Author
Journal
IF	>30 >20 >10 >5 all

Title	Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial.
Journal, issue, pages	PLoS Pathog, Vol. 13, Issue 2, Page e1006182, Year 2017
Publish date	Feb 24, 2017
Authors	David Easterhoff / M Anthony Moody / Daniela Fera / Hao Cheng / Margaret Ackerman / Kevin Wiehe / Kevin O Saunders / Justin Pollara / Nathan Vandergrift / Rob Parks / Jerome Kim / Nelson L Michael / Robert J O'Connell / Jean-Louis Excler / Merlin L Robb / Sandhya Vasan / Supachai Rerks-Ngarm / Jaranit Kaewkungwal / Punnee Pitisuttithum / Sorachai Nitayaphan / Faruk Sinangil / James Tartaglia / Sanjay Phogat / Thomas B Kepler / S Munir Alam / Hua-Xin Liao / Guido Ferrari / Michael S Seaman / David C Montefiori / Georgia D Tomaras / Stephen C Harrison / Barton F Haynes /
PubMed Abstract	The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is ...The canary pox vector and gp120 vaccine (ALVAC-HIV and AIDSVAX B/E gp120) in the RV144 HIV-1 vaccine trial conferred an estimated 31% vaccine efficacy. Although the vaccine Env AE.A244 gp120 is antigenic for the unmutated common ancestor of V1V2 broadly neutralizing antibody (bnAbs), no plasma bnAb activity was induced. The RV305 (NCT01435135) HIV-1 clinical trial was a placebo-controlled randomized double-blinded study that assessed the safety and efficacy of vaccine boosting on B cell repertoires. HIV-1-uninfected RV144 vaccine recipients were reimmunized 6-8 years later with AIDSVAX B/E gp120 alone, ALVAC-HIV alone, or a combination of ALVAC-HIV and AIDSVAX B/E gp120 in the RV305 trial. Env-specific post-RV144 and RV305 boost memory B cell VH mutation frequencies increased from 2.9% post-RV144 to 6.7% post-RV305. The vaccine was well tolerated with no adverse events reports. While post-boost plasma did not have bnAb activity, the vaccine boosts expanded a pool of envelope CD4 binding site (bs)-reactive memory B cells with long third heavy chain complementarity determining regions (HCDR3) whose germline precursors and affinity matured B cell clonal lineage members neutralized the HIV-1 CRF01 AE tier 2 (difficult to neutralize) primary isolate, CNE8. Electron microscopy of two of these antibodies bound with near-native gp140 trimers showed that they recognized an open conformation of the Env trimer. Although late boosting of RV144 vaccinees expanded a novel pool of neutralizing B cell clonal lineages, we hypothesize that boosts with stably closed trimers would be necessary to elicit antibodies with greater breadth of tier 2 HIV-1 strains. TRIAL REGISTRATION: ClinicalTrials.gov NCT01435135.
External links	PLoS Pathog / PubMed:28235027 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	2.501 - 28.1 Å
Structure data	EMDB-8573: HIV-1 CH505 Transmitted Founder SOSIP.664 Env trimer in Complex with the DH576 Fab from the RV305 Trial Method: EM (single particle) / Resolution: 28.1 Å PDB-5uix: Crystal Structure of the DH576 CD4bs Fab (unliganded) from the RV305 HIV Vaccine Trial Method: X-RAY DIFFRACTION / Resolution: 2.501 Å
Chemicals	ChemComp-HOH: WATER / Water
Source	homo sapiens (human)
Keywords	IMMUNE SYSTEM / FAB FRAGMENT / HIV-1 / ANTIBODY