The stem of vesicular stomatitis virus G can be replaced with the HIV-1 Env membrane-proximal external region without loss of G function or membrane-proximal external region antigenic properties. Academic Article uri icon

Overview

abstract

  • The structure of the HIV-1 envelope membrane-proximal external region (MPER) is influenced by its association with the lipid bilayer on the surface of virus particles and infected cells. To develop a replicating vaccine vector displaying MPER sequences in association with membrane, Env epitopes recognized by the broadly neutralizing antibodies 2F5, 4E10, or both were grafted into the membrane-proximal stem region of the vesicular stomatitis virus (VSV) glycoprotein (G). VSV encoding functional G-MPER chimeras based on G from the Indiana or New Jersey serotype propagated efficiently, although grafting of both epitopes (G-2F5-4E10) modestly reduced replication and resulted in the acquisition of one to two adaptive mutations in the grafted MPER sequence. Monoclonal antibodies 2F5 and 4E10 efficiently neutralized VSV G-MPER vectors and bound to virus particles in solution, indicating that the epitopes were accessible in the preattachment form of the G-MPER chimeras. Overall, our results showed that the HIV Env MPER could functionally substitute for the VSV G-stem region implying that both perform similar functions even though they are from unrelated viruses. Furthermore, we found that the MPER sequence grafts induced low but detectable MPER-specific antibody responses in rabbits vaccinated with live VSV, although additional vector and immunogen modifications or use of a heterologous prime-boost vaccination regimen will be required to increase the magnitude of the immune response.

authors

  • Lorenz, Ivo
  • Nguyen, Hanh T
  • Kemelman, Marina
  • Lindsay, Ross W
  • Yuan, Maoli
  • Wright, Kevin J
  • Arendt, Heather
  • Back, Jaap Willem
  • DeStefano, Joanne
  • Hoffenberg, Simon
  • Morrow, Gavin
  • Jurgens, Christy K
  • Phogat, Sanjay K
  • Zamb, Timothy J
  • Parks, Christopher L

publication date

  • April 9, 2014

Research

keywords

  • HIV Antibodies
  • Membrane Glycoproteins
  • Vesiculovirus
  • Viral Envelope Proteins
  • env Gene Products, Human Immunodeficiency Virus

Identity

PubMed Central ID

  • PMC4208592

Scopus Document Identifier

  • 84931462128

Digital Object Identifier (DOI)

  • 10.1089/AID.2013.0206

PubMed ID

  • 24597516

Additional Document Info

volume

  • 30

issue

  • 11