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Title | Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization. |
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Journal, issue, pages | Cell, Vol. 178, Issue 3, Page 567-584.e19, Year 2019 |
Publish date | Jul 25, 2019 |
Authors | Rui 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 Abstract | 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 ...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 links | Cell / PubMed:31348886 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.99 - 4.3 Å |
Structure data | EMDB-20189, PDB-6osy: EMDB-20191, PDB-6ot1: EMDB-8977, PDB-6mpg: 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 EMDB-9319, PDB-6n1v: EMDB-9320, PDB-6n1w: EMDB-9359, PDB-6nf2: PDB-6mqc: PDB-6mqe: PDB-6mqm: PDB-6mqr: PDB-6mqs: PDB-6n16: |
Chemicals | ChemComp-NAG: ChemComp-HOH: ChemComp-SO4: ChemComp-CA: |
Source |
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Keywords | VIRAL 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 |