In vivo gp41 antibodies targeting the 2F5 monoclonal antibody epitope mediate human immunodeficiency virus type 1 neutralization breadth.
The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both targeting the highly conserved human immunodeficiency virus type 1 (HIV-1) envelope membrane proximal external region (MPER), are among the MAbs with the broadest heterologous neutralizing activity and are of considerable interest for HIV-1 vaccine development. We have identified serum antibodies from an HIV-infected subject that both were broadly neutralizing and specifically targeted MPER epitopes that overlap the 2F5 epitope. These MPER-specific antibodies were made 15 to 20 months following transmission and concomitantly with the development of autoantibodies. Our findings suggest that multiple events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be required for induction of broadly reactive gp41 MPER antibodies in natural infection.
Shen
Xiaoying
X
Duke Human Vaccine Institute, Duke University Medicine Center, Durham, NC 27710, USA.
Parks
Robert J
RJ
Montefiori
David C
DC
Kirchherr
Jennifer L
JL
Keele
Brandon F
BF
Decker
Julie M
JM
Blattner
William A
WA
Gao
Feng
F
Weinhold
Kent J
KJ
Hicks
Charles B
CB
Greenberg
Michael L
ML
Hahn
Beatrice H
BH
Shaw
George M
GM
Haynes
Barton F
BF
Tomaras
Georgia D
GD
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; C514787:gp41 protein, Human immunodeficiency virus 1