Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
| العنوان: | Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose |
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| المؤلفون: | Francis J. Novembre, Victoria R. Polonis, David C. Montefiori, Welkin E. Johnson, Siddappa N. Byrareddy, Sarah J. Ratcliffe, Vivekanandan Shanmuganathan, Samir K. Lakhashe, Marjorie Robert-Guroff, Gary Landucci, Tania Brandstoetter, Miroslawa Bilska, Robert A. Rasmussen, Girish Hemashettar, Francois Villinger, Hemant K. Vyas, John K. Yoon, Swati Thorat, Jennifer D. Watkins, Ruth M. Ruprecht, Muhammad Mukhtar, Anton M Sholukh, Donald N. Forthal, Hildegund C.J. Ertl, Iskra Tuero |
| المصدر: | Retrovirology Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Lakhashe, Samir K; Rasmussen, Robert A; et al.(2014). Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose. Retrovirology, 11(1), 8. doi: 10.1186/1742-4690-11-8. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/26b3r1nc Sholukh, Anton M; Byrareddy, Siddappa N; Shanmuganathan, Vivekanandan; Hemashettar, Girish; Lakhashe, Samir K; Rasmussen, Robert A; et al.(2014). Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose. Retrovirology, 11, 8-8. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/08b9q3s1 |
| بيانات النشر: | BioMed Central, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Immunogen, Cross Protection, hiv-infection, HIV Antibodies, medicine.disease_cause, Immunoglobulin G, Non-human primate model hiv-1/siv chimeric virus, 0302 clinical medicine, Medicine and Health Sciences, 030212 general & internal medicine, 0303 health sciences, education.field_of_study, biology, Life Sciences, Heterologous R5 SHIV clade C challenge, 3. Good health, Infectious Diseases, Treatment Outcome, Simian Immunodeficiency Virus, Non-human primate model, SHIVIG, Population, Heterologous, envelope glycoprotein, Viremia, Virus, 03 medical and health sciences, rhesus macaques, Virology, medicine, Animals, neutralizing antibodies, education, 030304 developmental biology, Acquired Immunodeficiency Syndrome, replication-competent, Research, nonneutralizing antibodies, mediated enhancement, Passive immunization, Immunization, Passive, Simian immunodeficiency virus, medicine.disease, Antibodies, Neutralizing, Macaca mulatta, Macaque model, Disease Models, Animal, clade-c infection, vaccine development, Polyclonal antibodies, Immunology, Enhancement of infection, biology.protein, HIV-1 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1742-4690 |
| DOI: | 10.1186/1742-4690-11-8. |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdbfbd3dfcfefbf987ae8832676a6845 http://europepmc.org/articles/PMC3905655 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fdbfbd3dfcfefbf987ae8832676a6845 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17424690 |
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| DOI: | 10.1186/1742-4690-11-8. |