Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L

Ann J. Hessell, Eva G. Rakasz, David M. Tehrani, Michael Huber, Kimberly L. Weisgrau, Gary Landucci, Donald N. Forthal, Wayne C. Koff, Pascal Poignard, David Watkins, Dennis R. Burton

Research output: Contribution to journalArticle

244 Citations (Scopus)

Abstract

The membrane-proximal external region (MPER) of HIV-1, located at the C terminus of the gp41 ectodomain, is conserved and crucial for viral fusion. Three broadly neutralizing monoclonal antibodies (bnMAbs), 2F5, 4E10, and Z13e1, are directed against linear epitopes mapped to the MPER, making this conserved region an important potential vaccine target. However, no MPER antibodies have been definitively shown to provide protection against HIV challenge. Here, we show that both MAbs 2F5 and 4E10 can provide complete protection against mucosal simian-human immunodeficiency virus (SHIV) challenge in macaques. MAb 2F5 or 4E10 was administered intravenously at 50 mg/kg to groups of six male Indian rhesus macaques 1 day prior to and again 1 day following intrarectal challenge with SHIVBa-L. In both groups, five out of six animals showed complete protection and sterilizing immunity, while for one animal in each group a low level of viral replication following challenge could not be ruled out. The study confirms the protective potential of 2F5 and 4E10 and supports emphasis on HIV immunogen design based on the MPER region of gp41.

Original languageEnglish
Pages (from-to)1302-1313
Number of pages12
JournalJournal of Virology
Volume84
Issue number3
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

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Simian Immunodeficiency Virus
Human immunodeficiency virus
Human immunodeficiency virus 1
Neutralizing Antibodies
neutralizing antibodies
HIV-1
monoclonal antibodies
Monoclonal Antibodies
HIV
Membranes
virus replication
Macaca mulatta
Macaca
epitopes
animals
vaccines
antigens
antibodies
Epitopes
Immunity

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. / Hessell, Ann J.; Rakasz, Eva G.; Tehrani, David M.; Huber, Michael; Weisgrau, Kimberly L.; Landucci, Gary; Forthal, Donald N.; Koff, Wayne C.; Poignard, Pascal; Watkins, David; Burton, Dennis R.

In: Journal of Virology, Vol. 84, No. 3, 01.02.2010, p. 1302-1313.

Research output: Contribution to journalArticle

Hessell, Ann J. ; Rakasz, Eva G. ; Tehrani, David M. ; Huber, Michael ; Weisgrau, Kimberly L. ; Landucci, Gary ; Forthal, Donald N. ; Koff, Wayne C. ; Poignard, Pascal ; Watkins, David ; Burton, Dennis R. / Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. In: Journal of Virology. 2010 ; Vol. 84, No. 3. pp. 1302-1313.
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