HIV-1- specific IgA monoclonal antibodies from an HIV-1 vaccinee mediate galactosylceramide blocking and phagocytosis

Saintedym Wills, Kwan Ki Hwang, Pinghuang Liu, S. Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, Judith T. Lucas, Robert Parks, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Jaranit Kaewkungwal, Rasmi Thomas, Jerome H. Kim, Nelson L. Michael, Merlin L. Robb, Mike McRaven, David C. Montefiori, Thomas J. HopeHua Xin Liao, M. Anthony Moody, Guido Ferrari, Barton F. Haynes, S. Munir Alam, Mattia Bonsignori, Georgia D. Tomaras*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Vaccine-elicited humoral immune responses comprise an array of antibody forms and specificities, with only a fraction contributing to protective host immunity. Elucidation of antibody effector functions responsible for protective immunity against human immunodeficiency virus type 1 (HIV-1) acquisition is a major goal for the HIV-1 vaccine field. Immunoglobulin A (IgA) is an important part of the host defense against pathogens; however, little is known about the role of vaccineelicited IgA and its capacity to mediate antiviral functions. To identify the antiviral functions of HIV-1-specific IgA elicited by vaccination, we cloned HIV-1 envelopespecific IgA monoclonal antibodies (MAbs) by memory B cell cultures from peripheral blood mononuclear cells from an RV144 vaccinee and produced two IgA clonal cell lines (HG129 and HG130) producing native, nonrecombinant IgA MAbs. The HG129 and HG130 MAbs mediated phagocytosis by monocytes, and HG129 blocked HIV-1 Env glycoprotein binding to galactosylceramide, an alternative HIV-1 receptor. These findings elucidate potential antiviral functions of vaccine-elicited HIV-1 envelope-specific IgA that may act to block HIV-1 acquisition at the portal of entry by preventing HIV-1 binding to galactosylceramide and mediating antibody Fc receptor-mediated virion phagocytosis. Furthermore, these findings highlight the complex and diverse interactions of vaccine-elicited IgA with pathogens that depend on IgA fine specificity and form (e.g., multimeric or monomeric) in the systemic circulation and mucosal compartments.

Original languageEnglish (US)
Article numbere01552-17
JournalJournal of virology
Volume92
Issue number7
DOIs
StatePublished - Apr 1 2018

Keywords

  • B cell
  • HIV-1
  • IgA
  • Monoclonal antibodies
  • Nonneutralizing antibodies
  • Vaccine
  • Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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