Advertisement

 

 

Reproducing SIVΔnef vaccine correlates of protection: trimeric gp41 antibody concentrated at mucosal front lines.

Reproducing SIVΔnef vaccine correlates of protection: trimeric gp41 antibody concentrated at mucosal front lines.
Author Information (click to view)

Voss JE, Macauley MS, Rogers KA, Villinger F, Duan L, Shang L, Fink EA, Andrabi R, Colantonio AD, Robinson JE, Johnson RP, Burton DR, Haase AT,


Voss JE, Macauley MS, Rogers KA, Villinger F, Duan L, Shang L, Fink EA, Andrabi R, Colantonio AD, Robinson JE, Johnson RP, Burton DR, Haase AT, (click to view)

Voss JE, Macauley MS, Rogers KA, Villinger F, Duan L, Shang L, Fink EA, Andrabi R, Colantonio AD, Robinson JE, Johnson RP, Burton DR, Haase AT,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

AIDS (London, England) 30(16) 2427-2438

Abstract

Vaccination with SIVmac239Δnef provides robust protection against subsequent challenge with wild-type simian immunodeficiency virus (SIV), but safety issues have precluded designing an HIV-1 vaccine based on a live-attenuated virus concept. Safe immunogens and adjuvants that could reproduce identified immune correlates of SIVmac239Δnef protection therefore offer an alternative path for development of an HIV vaccine. Here we describe SIV envelope trimeric gp41 (gp41t) immunogens based on a protective correlate of antibodies to gp41t concentrated on the path of virus entry by the neonatal Fc receptor (FcRn) in cervical vaginal epithelium. We developed a gp41t immunogen-monophosphoryl lipid A adjuvant liposomal nanoparticle for intramuscular (i.m.) immunization and a gp41t-Fc immunogen for intranasal immunization for pilot studies in mice, rabbits, and rhesus macaques. Repeated immunizations to mimic persistent antigen exposure in infection elicited gp41t antibodies in rhesus macaques that were detectable in FcRn+ cervical vaginal epithelium, thus recapitulating one key feature of SIVmac239Δnef vaccinated and protected animals. Although this strategy did not reproduce the system of local production of antibody in SIVmac239Δnef-vaccinated animals, passive immunization experiments supported the concept that sufficiently high levels of antibody can be concentrated by the FcRn at mucosal frontlines, thus setting the stage for assessing protection against vaginal challenge by gp41t immunization.

Submit a Comment

Your email address will not be published. Required fields are marked *

1 × three =

[ HIDE/SHOW ]