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HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis.

Publication ,  Journal Article
Wills, S; Hwang, K-K; Liu, P; Dennison, SM; Tay, MZ; Shen, X; Pollara, J; Lucas, JT; Parks, R; Rerks-Ngarm, S; Pitisuttithum, P; Nitayapan, S ...
Published in: J Virol
April 1, 2018

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 vaccine-elicited 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 envelope-specific 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.IMPORTANCE Host-pathogen interactions in vivo involve numerous immune mechanisms that can lead to pathogen clearance. Understanding the nature of antiviral immune mechanisms can inform the design of efficacious HIV-1 vaccine strategies. Evidence suggests that both neutralizing and nonneutralizing antibodies can mediate some protection against HIV in animal models. Although numerous studies have characterized the functional properties of HIV-1-specific IgG, more studies are needed on the functional attributes of HIV-1-specific IgA, specifically for vaccine-elicited IgA. Characterization of the functional properties of HIV-1 Env-specific IgA monoclonal antibodies from human vaccine clinical trials are critical toward understanding the capacity of the host immune response to block HIV-1 acquisition.

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Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

April 1, 2018

Volume

92

Issue

7

Location

United States

Related Subject Headings

  • Virology
  • Phagocytosis
  • Immunoglobulin A
  • Humans
  • HIV-1
  • HIV Antibodies
  • Galactosylceramides
  • Cell Line
  • Antibodies, Monoclonal
  • Antibodies, Blocking
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wills, S., Hwang, K.-K., Liu, P., Dennison, S. M., Tay, M. Z., Shen, X., … Tomaras, G. D. (2018). HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis. J Virol, 92(7). https://doi.org/10.1128/JVI.01552-17
Wills, Saintedym, Kwan-Ki Hwang, Pinghuang Liu, S Moses Dennison, Matthew Zirui Tay, Xiaoying Shen, Justin Pollara, et al. “HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis.J Virol 92, no. 7 (April 1, 2018). https://doi.org/10.1128/JVI.01552-17.
Wills S, Hwang K-K, Liu P, Dennison SM, Tay MZ, Shen X, et al. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis. J Virol. 2018 Apr 1;92(7).
Wills, Saintedym, et al. “HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis.J Virol, vol. 92, no. 7, Apr. 2018. Pubmed, doi:10.1128/JVI.01552-17.
Wills S, Hwang K-K, Liu P, Dennison SM, Tay MZ, Shen X, Pollara J, Lucas JT, Parks R, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Kaewkungwal J, Thomas R, Kim JH, Michael NL, Robb ML, McRaven M, Montefiori DC, Hope TJ, Liao H-X, Moody MA, Ferrari G, Haynes BF, Alam SM, Bonsignori M, Tomaras GD. HIV-1-Specific IgA Monoclonal Antibodies from an HIV-1 Vaccinee Mediate Galactosylceramide Blocking and Phagocytosis. J Virol. 2018 Apr 1;92(7).

Published In

J Virol

DOI

EISSN

1098-5514

Publication Date

April 1, 2018

Volume

92

Issue

7

Location

United States

Related Subject Headings

  • Virology
  • Phagocytosis
  • Immunoglobulin A
  • Humans
  • HIV-1
  • HIV Antibodies
  • Galactosylceramides
  • Cell Line
  • Antibodies, Monoclonal
  • Antibodies, Blocking