title: Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques.
abstract: Simian-human immunodeficiency virus (SHIV) models for human immunodeficiency virus (HIV) infection have been widely used in passive studies with HIV neutralizing antibodies (NAbs) to test for protection against infection. However, because SHIV-infected adult macaques often rapidly control plasma viremia and any resulting pathogenesis is minor, the model has been unsuitable for studying the impact of antibodies on pathogenesis in infected animals. We found that SHIVSF162P3 infection in 1-month-old rhesus macaques not only results in high persistent plasma viremia but also leads to very rapid disease progression within 12 to 16 weeks. In this model, passive transfer of high doses of neutralizing IgG (SHIVIG) prevents infection. Here, we show that at lower doses, SHIVIG reduces both plasma and peripheral blood mononuclear cell (PBMC)-associated viremia and mitigates pathogenesis in infected animals. Moreover, production of endogenous NAbs correlated with lower set-point viremia and 100% survival of infected animals. New SHIV models are needed to investigate whether passively transferred antibodies or antibodies elicited by vaccination that fall short of providing sterilizing immunity impact disease progression or influence immune responses. The 1-month-old rhesus macaque SHIV model of infection provides a new tool to investigate the effects of antibodies on viral replication and clearance, mechanisms of B cell maintenance, and the induction of adaptive immunity in disease progression.
authors.affiliation: Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Jaworski
authors.forename: James
authors.initials: J
authors.lastname: Kobie
authors.forename: Zachary
authors.initials: Z
authors.lastname: Brower
authors.forename: Delphine C
authors.initials: DC
authors.lastname: Malherbe
authors.forename: Gary
authors.initials: G
authors.lastname: Landucci
authors.forename: William F
authors.initials: WF
authors.lastname: Sutton
authors.forename: Biwei
authors.initials: B
authors.lastname: Guo
authors.forename: Jason S
authors.initials: JS
authors.lastname: Reed
authors.forename: Enrique J
authors.initials: EJ
authors.lastname: Leon
authors.forename: Flora
authors.initials: F
authors.lastname: Engelmann
authors.forename: Bo
authors.initials: B
authors.lastname: Zheng
authors.forename: Al
authors.initials: A
authors.lastname: Legasse
authors.forename: Byung
authors.initials: B
authors.lastname: Park
authors.forename: Mary
authors.initials: M
authors.lastname: Dickerson
authors.forename: Anne D
authors.initials: AD
authors.lastname: Lewis
authors.forename: Lois M A
authors.initials: LM
authors.lastname: Colgin
authors.forename: Michael
authors.initials: M
authors.lastname: Axthelm
authors.forename: Ilhem
authors.initials: I
authors.lastname: Messaoudi
authors.forename: Jonah B
authors.initials: JB
authors.lastname: Sacha
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Donald N
authors.initials: DN
authors.lastname: Forthal
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Hessell
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Haigwood
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology*; D007963:Leukocytes, Mononuclear; D008214:Lymphocytes / Q000276:immunology* / Q000821:virology; D008253:Macaca mulatta; D009500:Neutralization Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity; D015996:Survival Rate; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000276:immunology* / Q000821:virology; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G