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TitleAntibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization.
Journal, issue, pagesCell, Vol. 178, Issue 3, Page 567-584.e19, Year 2019
Publish dateJul 25, 2019
AuthorsRui Kong / Hongying Duan / Zizhang Sheng / Kai Xu / Priyamvada Acharya / Xuejun Chen / Cheng Cheng / Adam S Dingens / Jason Gorman / Mallika Sastry / Chen-Hsiang Shen / Baoshan Zhang / Tongqing Zhou / Gwo-Yu Chuang / Cara W Chao / Ying Gu / Alexander J Jafari / Mark K Louder / Sijy O'Dell / Ariana P Rowshan / Elise G Viox / Yiran Wang / Chang W Choi / Martin M Corcoran / Angela R Corrigan / Venkata P Dandey / Edward T Eng / Hui Geng / Kathryn E Foulds / Yicheng Guo / Young D Kwon / Bob Lin / Kevin Liu / Rosemarie D Mason / Martha C Nason / Tiffany Y Ohr / Li Ou / Reda Rawi / Edward K Sarfo / Arne Schön / John P Todd / Shuishu Wang / Hui Wei / Winston Wu / / James C Mullikin / Robert T Bailer / Nicole A Doria-Rose / Gunilla B Karlsson Hedestam / Diana G Scorpio / Julie Overbaugh / Jesse D Bloom / Bridget Carragher / Clinton S Potter / Lawrence Shapiro / Peter D Kwong / John R Mascola /
PubMed AbstractThe vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be ...The vaccine-mediated elicitation of antibodies (Abs) capable of neutralizing diverse HIV-1 strains has been a long-standing goal. To understand how broadly neutralizing antibodies (bNAbs) can be elicited, we identified, characterized, and tracked five neutralizing Ab lineages targeting the HIV-1-fusion peptide (FP) in vaccinated macaques over time. Genetic and structural analyses revealed two of these lineages to belong to a reproducible class capable of neutralizing up to 59% of 208 diverse viral strains. B cell analysis indicated each of the five lineages to have been initiated and expanded by FP-carrier priming, with envelope (Env)-trimer boosts inducing cross-reactive neutralization. These Abs had binding-energy hotspots focused on FP, whereas several FP-directed Abs induced by immunization with Env trimer-only were less FP-focused and less broadly neutralizing. Priming with a conserved subregion, such as FP, can thus induce Abs with binding-energy hotspots coincident with the target subregion and capable of broad neutralization.
External linksCell / PubMed:31348886 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.99 - 4.3 Å
Structure data

EMDB-20189, PDB-6osy:
Cryo-EM structure of vaccine-elicited antibody 0PV-a.01 in complex with HIV-1 Env BG505 DS-SOSIP and antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-20191, PDB-6ot1:
Cryo-EM structure of vaccine-elicited antibody 0PV-b.01 in complex with HIV-1 Env BG505 DS-SOSIP and antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-8977, PDB-6mpg:
Cryo-EM structure at 3.2 A resolution of HIV-1 fusion peptide-directed antibody, A12V163-b.01, elicited by vaccination of Rhesus macaques, in complex with stabilized HIV-1 Env BG505 DS-SOSIP, which was also bound to antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 3.18 Å

EMDB-9189: Cryo-EM structure at 3.8 A resolution of HIV-1 fusion peptide-directed antibody, DF1W-a.01, elicited by vaccination of Rhesus macaques, in complex with stabilized HIV-1Env BG505 DS-SOSIP, which was also bound to antibodies VRC03 and PGT122
PDB-6mph: Cryo-EM structure at 3.8 A resolution of HIV-1 fusion peptide-directed antibody, DF1W-a.01, elicited by vaccination of Rhesus macaques, in complex with stabilized HIV-1 Env BG505 DS-SOSIP, which was also bound to antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-9319, PDB-6n1v:
Cryo-EM structure at 4.0 A resolution of vaccine-elicited antibody A12V163-a.01 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-9320, PDB-6n1w:
Cryo-EM structure at 4.2 A resolution of vaccine-elicited antibody DFPH-a.15 in complex with HIV-1 Env BG505 DS-SOSIP, and antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-9359, PDB-6nf2:
Cryo-EM structure of vaccine-elicited antibody 0PV-c.01 in complex with HIV-1 Env BG505 DS-SOSIP and antibodies VRC03 and PGT122
Method: EM (single particle) / Resolution: 3.7 Å

PDB-6mqc:
Vaccine-elicited NHP FP-targeting neutralizing antibody 0PV-c.01 in complex with FP (residue 512-519)
Method: X-RAY DIFFRACTION / Resolution: 1.99 Å

PDB-6mqe:
Vaccine-elicited NHP FP-targeting HIV neutralizing antibody DFPH-a.15 in complex with HIV fusion peptide (residue 512-519)
Method: X-RAY DIFFRACTION / Resolution: 2.459 Å

PDB-6mqm:
Vaccine-elicited NHP FP-targeting neutralizing antibody DF1W-a.01 in complex with HIV fusion peptide (residue 512-519)
Method: X-RAY DIFFRACTION / Resolution: 3.484 Å

PDB-6mqr:
Vaccine-elicited NHP FP-targeting neutralizing antibody 0PV-a.01 in complex with FP (residue 512-519)
Method: X-RAY DIFFRACTION / Resolution: 2.45 Å

PDB-6mqs:
Vaccine-elicited NHP FP-targeting HIV neutralizing antibody A12V163-a.01 in complex with HIV fusion peptide (residue 512-519)
Method: X-RAY DIFFRACTION / Resolution: 2.997 Å

PDB-6n16:
Vaccine-elicited NHP FP-targeting neutralizing antibody 0PV-b.01 in complex with HIV fusion peptide (residue 512-519)
Method: X-RAY DIFFRACTION / Resolution: 2.302 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

ChemComp-HOH:
WATER

ChemComp-SO4:
SULFATE ION

ChemComp-CA:
Unknown entry

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN / Complex / Fusion peptide / Neutralizing antibody / HIV-1 Envelope / IMMUNE SYSTEM / HIV / neutralizing / NHP / FP / vaccine / HIV-1 Env complex / fusion peptide-directed / HIV-1 / SOSIP

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