Intranasal vaccination with HBs and HBc protein combined with carboxyl vinyl polymer induces strong neutralizing antibody, anti-HBs IgA, and IFNG response

Biochem Biophys Res Commun. 2019 Nov 26;520(1):86-92. doi: 10.1016/j.bbrc.2019.09.072. Epub 2019 Sep 30.

Abstract

Hepatitis B virus (HBV) infection causes acute and chronic hepatitis, which is a major public health concern worldwide. Immunization methods incorporating hepatitis B surface-small (HBs-S) antigen and hepatitis B core antigen (HBc) have been proposed as candidate therapeutic vaccines, but the elimination of existing HBV infection remains a challenge. To enhance the efficacy of HBs and HBc vaccination, we investigated HBs-large (HBs-L) as an immunogen, and carboxyl vinyl polymer (CVP) as an excipient. HBs-S or HBs-L, in combination with HBc antigen, was administered subcutaneously (without CVP) or intranasally (with or without CVP) for the evaluation of immune response in the tree shrew, which is considered to be a suitable small animal model of HBV infection. Immunization with HBs-L antigen by either route induced a rapid IgG response. Intranasal immunization with HBs-S or HBs-L and HBc formulated with CVP strongly induced neutralizing antibody activity, IgA response, and HBc-specific expression of the interferon gamma-encoding gene. These data indicated the potential of HBs-L and HBc intranasal immunization with CVP, not only as a therapeutic vaccine, but also as a prophylactic vaccine candidate.

Keywords: Carboxyl vinyl polymer; HBs-L; Hepatitis B virus; Intranasal administration; Tree shrew; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Genotype
  • Hep G2 Cells
  • Hepatitis B / virology
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B virus
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin G / immunology
  • Interferon-gamma / immunology*
  • Liver / metabolism
  • Mice
  • Neutralization Tests
  • Polymers / chemistry
  • Tupaiidae

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • Polymers
  • Interferon-gamma