Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.
Walker
Laura M
LM
Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
Phogat
Sanjay K
SK
Chan-Hui
Po-Ying
PY
Wagner
Denise
D
Phung
Pham
P
Goss
Julie L
JL
Wrin
Terri
T
Simek
Melissa D
MD
Fling
Steven
S
Mitcham
Jennifer L
JL
Lehrman
Jennifer K
JK
Priddy
Frances H
FH
Olsen
Ole A
OA
Frey
Steven M
SM
Hammond
Phillip W
PW
Kaminsky
Stephen
S
Zamb
Timothy
T
Moyle
Matthew
M
Koff
Wayne C
WC
Poignard
Pascal
P
Burton
Dennis R
DR
D016915:AIDS Vaccines / Q000276:immunology*; D017954:Africa South of the Sahara; D000911:Antibodies, Monoclonal / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000276:immunology
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011994:Recombinant Proteins; C514793:gp120 protein, Human immunodeficiency virus 1; C514787:gp41 protein, Human immunodeficiency virus 1