Dataset Information

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

ABSTRACT: BACKGROUND:A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. RESULTS:SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P?=?0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. CONCLUSION:Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.

SUBMITTER: Sholukh AM

PROVIDER: S-EPMC3905655 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

Sholukh Anton M AM Byrareddy Siddappa N SN Shanmuganathan Vivekanandan V Hemashettar Girish G Lakhashe Samir K SK Rasmussen Robert A RA Watkins Jennifer D JD Vyas Hemant K HK Thorat Swati S Brandstoetter Tania T Mukhtar Muhammad M MM Yoon John K JK Novembre Francis J FJ Villinger Francois F Landucci Gary G Forthal Donald N DN Ratcliffe Sarah S Tuero Iskra I Robert-Guroff Marjorie M Polonis Victoria R VR Bilska Miroslawa M Montefiori David C DC Johnson Welkin E WE Ertl Hildegund C HC Ruprecht Ruth M RM

Retrovirology 20140120

<h4>Background</h4>A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed ...[more]

PMID: 24444350

Similar Datasets

Project description:We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. We immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses. For the protected RM, blood was collected before vaccination, on the day of first virus exposure and six weeks after last virus challenge. Lymph node and rectal pinch biopsies were performed before vaccination and six weeks after last virus challenge. Blood was collected in tempus tubes and processed immediately according to the manufacturer’s instructions and stored at -80C. The biopsy specimens were cut into small pieces and immediately placed into RNAlater solution (Qiagen, Valencia, CA) and also stored at -80C. Total RNA from blood, lymph node and rectal biopsies was extracted using RNAeasy extraction kits (Qiagen, Valencia, CA). cDNA labeling, hybridization, staining and scanning were performed according to the manufacturer’s instructions (Affymetrix, Santa Clara, CA) for rhesus gene expression arrays.

Dataset Information

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

Publications

Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets