title: Protection against high-dose highly pathogenic mucosal SIV challenge at very low serum neutralizing titers of the antibody-like molecule CD4-IgG2.
abstract: Passive transfer studies using monoclonal or polyclonal antibodies in the macaque model have been valuable for determining conditions for antibody protection against immunodeficiency virus challenge. Most studies have employed hybrid simian/human immunodeficiency virus (SHIV) challenge in conjunction with neutralizing human monoclonal antibodies. Passive protection against SIV, particularly the pathogenic prototype virus SIVmac239, has been little studied because of the paucity of neutralizing antibodies to this virus. Here, we show that the antibody-like molecule CD4-IgG2 potently neutralizes SIVmac239 in vitro. When administered by an osmotic pump to maintain concentrations given the short half-life of CD4-IgG2 in macaques, the molecule provided sterilizing immunity/protection against high-dose mucosal viral challenge to a high proportion of animals (5/7 at a 200 mg dose CD4-IgG2 and 3/6 at a 20 mg dose) at serum concentrations below 1.5 µg/ml. The neutralizing titers of such sera were predicted to be very low and indeed sera at a 1:4 dilution produced no neutralization in a pseudovirus assay. Macaque anti-human CD4 titers did develop weakly at later time points in some animals but were not associated with the level of protection against viral challenge. The results show that, although SIVmac239 is considered a highly pathogenic virus for which vaccine-induced T cell responses in particular have provided limited benefit against high dose challenge, the antibody-like CD4-IgG2 molecule at surprisingly low serum concentration affords sterilizing immunity/protection to a majority of animals.
authors: Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America. poignard@scripps.edu
authors: Pascal
authors: P
authors: Poignard
authors: Brian
authors: B
authors: Moldt
authors: Karla
authors: K
authors: Maloveste
authors: Noëlie
authors: N
authors: Campos
authors: William C
authors: WC
authors: Olson
authors: Eva
authors: E
authors: Rakasz
authors: David I
authors: DI
authors: Watkins
authors: Dennis R
authors: DR
authors: Burton
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology; D015704:CD4 Antigens / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000097:blood* / Q000276:immunology; D007260:Infusion Pumps; D008253:Macaca mulatta; D008297:Male; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D007074:Immunoglobulin G