Increasing the breadth and potency of response to the seasonal influenza virus vaccine by immune complex immunization

Proc Natl Acad Sci U S A. 2017 Sep 19;114(38):10172-10177. doi: 10.1073/pnas.1707950114. Epub 2017 Sep 5.

Abstract

The main barrier to reduction of morbidity caused by influenza is the absence of a vaccine that elicits broad protection against different virus strains. Studies in preclinical models of influenza virus infections have shown that antibodies alone are sufficient to provide broad protection against divergent virus strains in vivo. Here, we address the challenge of identifying an immunogen that can elicit potent, broadly protective, antiinfluenza antibodies by demonstrating that immune complexes composed of sialylated antihemagglutinin antibodies and seasonal inactivated flu vaccine (TIV) can elicit broadly protective antihemagglutinin antibodies. Further, we found that an Fc-modified, bispecific monoclonal antibody against conserved epitopes of the hemagglutinin can be combined with TIV to elicit broad protection, thus setting the stage for a universal influenza virus vaccine.

Trial registration: ClinicalTrials.gov NCT01967238.

Keywords: CD23; TIV; immune complex; sialylated Fc; universal influenza vaccine.

Publication types

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

MeSH terms

  • Animals
  • Dogs
  • Female
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunoglobulin G / immunology*
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Mice, Inbred C57BL
  • Receptors, IgE / immunology*

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin G
  • Influenza Vaccines
  • Receptors, IgE
  • hemagglutinin, human influenza A virus

Associated data

  • ClinicalTrials.gov/NCT01967238