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Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects.

Publication ,  Journal Article
Huang, Y; Ferrari, G; Alter, G; Forthal, DN; Kappes, JC; Lewis, GK; Love, JC; Borate, B; Harris, L; Greene, K; Gao, H; Phan, TB; Landucci, G ...
Published in: J Immunol
December 15, 2016

Diverse Ab effector functions mediated by the Fc domain have been commonly associated with reduced risk of infection in a growing number of nonhuman primate and human clinical studies. This study evaluated the anti-HIV Ab effector activities in polyclonal serum samples from HIV-infected donors, VAX004 vaccine recipients, and healthy HIV-negative subjects using a variety of primary and cell line-based assays, including Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cell-mediated viral inhibition, and Ab-dependent cellular phagocytosis. Additional assay characterization was performed with a panel of Fc-engineered variants of mAb b12. The goal of this study was to characterize different effector functions in the study samples and identify assays that might most comprehensively and dependably capture Fc-mediated Ab functions mediated by different effector cell types and against different viral targets. Deployment of such assays may facilitate assessment of functionally unique humoral responses and contribute to identification of correlates of protection with potential mechanistic significance in future HIV vaccine studies. Multivariate and correlative comparisons identified a set of Ab-dependent cell-mediated viral inhibition and phagocytosis assays that captured different Ab activities and were distinct from a group of ADCC assays that showed a more similar response profile across polyclonal serum samples. The activities of a panel of b12 monoclonal Fc variants further identified distinctions among the ADCC assays. These results reveal the natural diversity of Fc-mediated Ab effector responses among vaccine recipients in the VAX004 trial and in HIV-infected subjects, and they point to the potential importance of polyfunctional Ab responses.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2016

Volume

197

Issue

12

Start / End Page

4603 / 4612

Location

United States

Related Subject Headings

  • Virus Replication
  • Vaccination
  • Phagocytosis
  • Mutation
  • Immunology
  • Immunoglobulin Fc Fragments
  • Immunity, Humoral
  • Humans
  • HIV-1
  • HIV Infections
 

Citation

APA
Chicago
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Huang, Y., Ferrari, G., Alter, G., Forthal, D. N., Kappes, J. C., Lewis, G. K., … Ackerman, M. E. (2016). Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects. J Immunol, 197(12), 4603–4612. https://doi.org/10.4049/jimmunol.1601197
Huang, Yunda, Guido Ferrari, Galit Alter, Donald N. Forthal, John C. Kappes, George K. Lewis, J Christopher Love, et al. “Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects.J Immunol 197, no. 12 (December 15, 2016): 4603–12. https://doi.org/10.4049/jimmunol.1601197.
Huang Y, Ferrari G, Alter G, Forthal DN, Kappes JC, Lewis GK, et al. Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects. J Immunol. 2016 Dec 15;197(12):4603–12.
Huang, Yunda, et al. “Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects.J Immunol, vol. 197, no. 12, Dec. 2016, pp. 4603–12. Pubmed, doi:10.4049/jimmunol.1601197.
Huang Y, Ferrari G, Alter G, Forthal DN, Kappes JC, Lewis GK, Love JC, Borate B, Harris L, Greene K, Gao H, Phan TB, Landucci G, Goods BA, Dowell KG, Cheng HD, Bailey-Kellogg C, Montefiori DC, Ackerman ME. Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects. J Immunol. 2016 Dec 15;197(12):4603–4612.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2016

Volume

197

Issue

12

Start / End Page

4603 / 4612

Location

United States

Related Subject Headings

  • Virus Replication
  • Vaccination
  • Phagocytosis
  • Mutation
  • Immunology
  • Immunoglobulin Fc Fragments
  • Immunity, Humoral
  • Humans
  • HIV-1
  • HIV Infections