PET/CT Targeted Tissue Sampling Reveals Intravenously Administered HGN194 IgG1 Affects HIV Distribution after Rectal Exposure

Roslyn A. Taylor, Sixia Xiao, Ann M. Carias, Michael D. McRaven, Divya N. Thakkar, Mariluz Araínga, Ramon Lorenzo-Redondo, Edward J. Allen, Kenneth A. Rogers, Sidath C. Kumarapperuma, Siqi Gong, Meegan R. Anderson, Yanique Thomas, Patrick J. Madden, Davide Corti, Elisabetta Cameroni, Antonio Lanzavecchia, Beth Goins, Peter Fox, Francois J. VillingerRuth M. Ruprecht, Thomas J. Hope

Research output: Contribution to journalArticlepeer-review

Abstract

Neutralizing monoclonal antibodies hold great potential for prevention of human immunodeficiency virus (HIV) acquisition. IgG is the most abundant antibody in human serum, has a long half-life, and potent effector functions, making it a prime candidate for an HIV prevention therapeutic. We combined Positron Emission Tomography imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-green fluorescent protein HIV (PA-GFPBaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interactionwithmucosal barriers and viral penetration in colorectal tissue 2 h after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found inmesenteric lymph nodes. Taken together, our results show that HGN194 IgG1 does not prevent virions from penetrating into the colorectal mucosa but may perturb HIV virion access to the lymphatic system.

Original languageEnglish (US)
Pages (from-to)637-648
Number of pages12
JournalAIDS Research and Human Retroviruses
Volume40
Issue number11
DOIs
StatePublished - Nov 1 2024

Keywords

  • HIV transmission
  • antibodies
  • mucosal barriers
  • mucosal immunology

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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