IL-33 enhances the kinetics and quality of the antibody response to a DNA and protein-based HIV-1 Env vaccine

Vaccine. 2019 Apr 17;37(17):2322-2330. doi: 10.1016/j.vaccine.2019.03.044. Epub 2019 Mar 27.

Abstract

Induction of a sustained and broad antibody (Ab) response is a major goal in developing a protective HIV-1 vaccine. DNA priming alone shows reduced levels of immunogenicity; however, when combined with protein boosting is an attractive vaccination strategy for induction of humoral responses. Using the VC10014 DNA and protein-based vaccine consisting of HIV-1 envelope (Env) gp160 plasmids and trimeric gp140 proteins derived from an HIV-1 clade B infected subject who developed broadly neutralizing serum Abs, and which has been previously demonstrated to induce Tier 2 heterologous neutralizing Abs in rhesus macaques, we evaluated whether MPLA and IL-33 when administered during the DNA priming phase enhances the humoral response in mice. The addition of IL-33 during the gp160 DNA priming phase resulted in high titer gp120-specific plasma IgG after the first immunization. The IL-33 treated mice had higher plasma IgG Ab avidity, breadth, and durability after DNA and protein co-immunization with alum adjuvant as compared to MPLA and alum only treated mice. IL-33 was also associated with a significant IgM Env-specific response and expansion of peritoneal and splenic B-1b B cells. These results indicate that DNA priming in the presence of exogenous IL-33 qualitatively alters the HIV-1 Env-specific humoral response, improving the kinetics and breadth of potentially protective Ab.

Keywords: Antibody; Envelope; HIV-1; IL-33; IgM; Vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Animals
  • Antibody Formation / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Disease Models, Animal
  • Female
  • HIV Antibodies / blood
  • HIV Antibodies / immunology*
  • HIV Infections / immunology*
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Immunization
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Immunoglobulin M / blood
  • Immunoglobulin M / immunology
  • Interleukin-33 / metabolism*
  • Mice
  • Vaccines, DNA / immunology
  • env Gene Products, Human Immunodeficiency Virus / genetics
  • env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-33
  • Vaccines, DNA
  • env Gene Products, Human Immunodeficiency Virus