Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1.
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
Wu
Xueling
X
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Yang
Zhi-Yong
ZY
Li
Yuxing
Y
Hogerkorp
Carl-Magnus
CM
Schief
William R
WR
Seaman
Michael S
MS
Zhou
Tongqing
T
Schmidt
Stephen D
SD
Wu
Lan
L
Xu
Ling
L
Longo
Nancy S
NS
McKee
Krisha
K
O'Dell
Sijy
S
Louder
Mark K
MK
Wycuff
Diane L
DL
Feng
Yu
Y
Nason
Martha
M
Doria-Rose
Nicole
N
Connors
Mark
M
Kwong
Peter D
PD
Roederer
Mario
M
Wyatt
Richard T
RT
Nabel
Gary J
GJ
Mascola
John R
JR
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D003429:Cross Reactions; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D050438:Genes, Immunoglobulin Heavy Chain; D050439:Genes, Immunoglobulin Light Chain; D015483:HIV Antibodies / Q000276:immunology* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins