title: 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.
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 SHIV(Ba-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.
authors.affiliation: Department of Immunology and Microbial Science and the International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Hessell
authors.forename: Eva G
authors.initials: EG
authors.lastname: Rakasz
authors.forename: David M
authors.initials: DM
authors.lastname: Tehrani
authors.forename: Michael
authors.initials: M
authors.lastname: Huber
authors.forename: Kimberly L
authors.initials: KL
authors.lastname: Weisgrau
authors.forename: Gary
authors.initials: G
authors.lastname: Landucci
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Koff
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
authors.forename: David I
authors.initials: DI
authors.lastname: Watkins
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006367:HeLa Cells; D006801:Humans; D018928:Immunity, Mucosal; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015700:HIV Envelope Protein gp41