|Title||Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Tian M, Cheng C, Chen X, Duan H, Cheng H-L, Dao M, Sheng Z, Kimble M, Wang L, Lin S, Schmidt SD, Du Z, M Joyce G, Chen Y, Dekosky BJ, Chen Y, Normandin E, Cantor E, Chen RE, Doria-Rose NA, Zhang Y, Shi W, Kong W-P, Choe M, Henry AR, Laboune F, Georgiev IS, Huang P-Y, Jain S, McGuire AT, Georgeson E, Menis S, Douek DC, Schief WR, Stamatatos L, Kwong PD, Shapiro L, Haynes BF, Mascola JR, Alt FW|
The design of immunogens that elicit broadly reactive neutralizing antibodies (bnAbs) has been a major obstacle to HIV-1 vaccine development. One approach to assess potential immunogens is to use mice expressing precursors of human bnAbs as vaccination models. The bnAbs of the VRC01-class derive from the IGHV1-2 immunoglobulin heavy chain and neutralize a wide spectrum of HIV-1 strains via targeting the CD4 binding site of the envelope glycoprotein gp120. We now describe a mouse vaccination model that allows a germline human IGHV1-2(∗)02 segment to undergo normal V(D)J recombination and, thereby, leads to the generation of peripheral B cells that express a highly diverse repertoire of VRC01-related receptors. When sequentially immunized with modified gp120 glycoproteins designed to engage VRC01 germline and intermediate antibodies, IGHV1-2(∗)02-rearranging mice, which also express a VRC01-antibody precursor light chain, can support the affinity maturation of VRC01 precursor antibodies into HIV-neutralizing antibody lineages.
|Grant List||R01 AI020047 / AI / NIAID NIH HHS / United States |
U19 AI109632 / AI / NIAID NIH HHS / United States
P01 AI094419 / AI / NIAID NIH HHS / United States
UM1 AI100645 / AI / NIAID NIH HHS / United States
R01 AI077595 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ HHMI / HHMI / United States
P01 AI104722 / AI / NIAID NIH HHS / United States
Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.