A multiplex assay for detection of SHIV plasma and mucosal IgG and IgA

J Immunol Methods. 2017 Nov:450:34-40. doi: 10.1016/j.jim.2017.07.008. Epub 2017 Jul 25.

Abstract

Evaluating antibody maturation provides valuable data to characterize immune responses to HIV infection and can provide insight into biomedical intervention efficacy. It is important to develop assays that evaluate antibody maturation in both plasma and mucosal compartments. The nonhuman primate model provides a controlled system to collect temporal data that are integral to assessing intervention strategies. We report the development of a novel multiplex assay, based on the Bio-Plex platform, to evaluate plasma and mucosal IgG and IgA avidity and maturation against simian/human immunodeficiency virus (SHIV) in this controlled system. Vaginal mucosa and plasma samples were collected from a prior study evaluating the efficacy of a tenofovir disoproxil fumarate (TDF) intravaginal ring (IVR) against SHIVSF162P3 challenge in female pigtailed macaques. For validation of the multiplex assay, specimens from six SHIV-infected placebo animals and one TDF breakthrough animal were evaluated. For SHIV and HIV envelope analytes, antibody levels and avidity in both compartments continued to mature post-infection. Maturation of IgG and IgA levels was similar in each compartment, however, mucosal antibody levels tended to be more variable. This SHIV assay elucidates IgG/IgA antibody kinetics in the plasma and vaginal mucosa and will be a valuable tool in vaccine and other biomedical intervention studies in the nonhuman primate model.

Keywords: Antibody affinity; HIV antibodies; Immunoassay; Mucous membrane; Nonhuman primate; Simian immunodeficiency virus.

Publication types

  • Validation Study

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adenoviruses, Simian / drug effects
  • Adenoviruses, Simian / immunology*
  • Administration, Intravaginal
  • Animals
  • Anti-HIV Agents / administration & dosage
  • Biomarkers / blood
  • Disease Models, Animal
  • Female
  • HIV Antibodies / blood*
  • Host-Pathogen Interactions
  • Immunity, Humoral
  • Immunity, Mucosal
  • Immunoassay / methods*
  • Immunoglobulin A / blood*
  • Immunoglobulin G / blood*
  • Macaca nemestrina
  • Mucous Membrane / immunology*
  • Mucous Membrane / virology
  • Phosphorous Acids / administration & dosage
  • Predictive Value of Tests
  • Reproducibility of Results
  • Seroconversion
  • Serologic Tests / methods*
  • Simian Acquired Immunodeficiency Syndrome / blood
  • Simian Acquired Immunodeficiency Syndrome / diagnosis*
  • Simian Acquired Immunodeficiency Syndrome / drug therapy
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Time Factors
  • Vagina / immunology*
  • Vagina / virology
  • Viral Load

Substances

  • 9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine
  • Anti-HIV Agents
  • Biomarkers
  • HIV Antibodies
  • Immunoglobulin A
  • Immunoglobulin G
  • Phosphorous Acids
  • Adenine