Details

Autor(en) / Beteiligte

• Kong, Rui
• Duan, Hongying
• Sheng, Zizhang
• Xu, Kai
• Acharya, Priyamvada
• Chen, Xuejun
• Cheng, Cheng
• Dingens, Adam S.
• Gorman, Jason
• Sastry, Mallika
• Shen, Chen-Hsiang
• Zhang, Baoshan
• Zhou, Tongqing
• Chuang, Gwo-Yu
• Chao, Cara W.
• Gu, Ying
• Jafari, Alexander J.
• Louder, Mark K.
• O’Dell, Sijy
• Rowshan, Ariana P.
• Viox, Elise G.
• Wang, Yiran
• Choi, Chang W.
• Corcoran, Martin M.
• Corrigan, Angela R.
• Dandey, Venkata P.
• Eng, Edward T.
• Geng, Hui
• Foulds, Kathryn E.
• Guo, Yicheng
• Kwon, Young D.
• Lin, Bob
• Liu, Kevin
• Mason, Rosemarie D.
• Nason, Martha C.
• Ohr, Tiffany Y.
• Ou, Li
• Rawi, Reda
• Sarfo, Edward K.
• Schön, Arne
• Todd, John P.
• Wang, Shuishu
• Wei, Hui
• Wu, Winston
• Mullikin, James C.
• Bailer, Robert T.
• Doria-Rose, Nicole A.
• Karlsson Hedestam, Gunilla B.
• Scorpio, Diana G.
• Overbaugh, Julie
• Bloom, Jesse D.
• Carragher, Bridget
• Potter, Clinton S.
• Shapiro, Lawrence
• Kwong, Peter D.
• Mascola, John R.

Titel

Antibody Lineages with Vaccine-Induced Antigen-Binding Hotspots Develop Broad HIV Neutralization

Ist Teil von

• Cell, 2019-07, Vol.178 (3), p.567-584.e19

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •Vaccine elicitation of FP-directed antibody that neutralizes up to 59% of HIV•Development for five NHP lineages of vaccine-induced broadly neutralizing antibodies•FP-carrier effective at priming and Env-trimer effective at maturing•Priming with a target subregion induces antibodies with target-interaction hotspots A cross-clade, cross-reactive HIV-1 neutralizing antibody with ∼59% neutralization breadth is elicited in macaques using a fusion-peptide-primed vaccine regimen, which focuses antibody-binding energy on a conserved viral epitope. Further phylogenetic antibody analysis provides insight into the eclipse phase of B cell development.