Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine

J Immunol. 2017 Jan 1;198(1):279-291. doi: 10.4049/jimmunol.1600173. Epub 2016 Nov 23.

Abstract

Vaccine adjuvant effects in the CD4-deficient condition largely remain unknown. We investigated the roles of combined monophosphoryl lipid A (MPL) and aluminum hydroxide (Alum) adjuvant (MPL+Alum) in inducing immunity after immunization of CD4 knockout (CD4KO) and wild-type (WT) mice with T-dependent influenza vaccine. MPL+Alum adjuvant mediated IgG isotype-switched Abs, IgG-secreting cell responses, and protection in CD4KO mice, which were comparable to those in WT mice. In contrast, Alum adjuvant effects were dependent on CD4+ T cells. MPL+Alum adjuvant was effective in recruiting monocytes and neutrophils as well as in protecting macrophages from Alum-mediated cell loss at the injection site in CD4KO mice. MPL+Alum appeared to attenuate MPL-induced inflammatory responses in WT mice, likely improving the safety. Additional studies in CD4-depleted WT mice and MHC class II KO mice suggest that MHC class II+ APCs contribute to providing alternative B cell help in the CD4-deficient condition in the context of MPL+Alum-adjuvanted vaccination.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Aluminum Hydroxide / immunology
  • Aluminum Hydroxide / pharmacology*
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology
  • Antigen-Presenting Cells / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Immunoglobulin Class Switching / drug effects
  • Immunoglobulin G / biosynthesis*
  • Influenza Vaccines / immunology*
  • Lipid A / analogs & derivatives*
  • Lipid A / immunology
  • Lipid A / pharmacology
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin G
  • Influenza Vaccines
  • Lipid A
  • Aluminum Hydroxide
  • monophosphoryl lipid A