Biomaterial Database

Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. 2021

Rena D Astronomo, and Maria P Lemos, and Sandeep R Narpala, and Julie Czartoski, and Lamar Ballweber Fleming, and Kelly E Seaton, and Madhu Prabhakaran, and Yunda Huang, and Yiwen Lu, and Katharine Westerberg, and Lily Zhang, and Mary K Gross, and John Hural, and Hong-Van Tieu, and Lindsey R Baden, and Scott Hammer, and Ian Frank, and Christina Ochsenbauer, and Nicole Grunenberg, and Julie E Ledgerwood, and Kenneth Mayer, and Georgia Tomaras, and Adrian B McDermott, and M Juliana McElrath

Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

BackgroundVRC01, a potent, broadly neutralizing monoclonal antibody, inhibits simian-HIV infection in animal models. The HVTN 104 study assessed the safety and pharmacokinetics of VRC01 in humans. We extend the clinical evaluation to determine intravenously infused VRC01 distribution and protective function at mucosal sites of HIV-1 entry.MethodsHealthy, HIV-1-uninfected men (n = 7) and women (n = 5) receiving VRC01 every 2 months provided mucosal and serum samples once, 4-13 days after infusion. Eleven male and 8 female HIV-seronegative volunteers provided untreated control samples. VRC01 levels were measured in serum, secretions, and tissue, and HIV-1 inhibition was determined in tissue explants.ResultsMedian VRC01 levels were quantifiable in serum (96.2 μg/mL or 1.3 pg/ng protein), rectal tissue (0.11 pg/ng protein), rectal secretions (0.13 pg/ng protein), vaginal tissue (0.1 pg/ng protein), and cervical secretions (0.44 pg/ng protein) from all recipients. VRC01/IgG ratios in male serum correlated with those in paired rectal tissue (r = 0.893, P = 0.012) and rectal secretions (r = 0.9643, P = 0.003). Ex vivo HIV-1Bal26 challenge infected 4 of 21 rectal explants from VRC01 recipients versus 20 of 22 from controls (P = 0.005); HIV-1Du422.1 infected 20 of 21 rectal explants from VRC01 recipients and 12 of 12 from controls (P = 0.639). HIV-1Bal26 infected 0 of 14 vaginal explants of VRC01 recipients compared with 23 of 28 control explants (P = 0.003).ConclusionIntravenous VRC01 distributes into the female genital and male rectal mucosa and retains anti-HIV-1 functionality, inhibiting a highly neutralization-sensitive but not a highly resistant HIV-1 strain in mucosal tissue. These findings lend insight into VRC01 mucosal infiltration and provide perspective on in vivo protective efficacy.FundingNational Institute of Allergy and Infectious Diseases and Bill & Melinda Gates Foundation.

UI	MeSH Term	Description	Entries
D007262	Infusions, Intravenous	The long-term (minutes to hours) administration of a fluid into the vein through venipuncture, either by letting the fluid flow by gravity or by pumping it.	Drip Infusions,Intravenous Drip,Intravenous Infusions,Drip Infusion,Drip, Intravenous,Infusion, Drip,Infusion, Intravenous,Infusions, Drip,Intravenous Infusion
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D009092	Mucous Membrane	An EPITHELIUM with MUCUS-secreting cells, such as GOBLET CELLS. It forms the lining of many body cavities, such as the DIGESTIVE TRACT, the RESPIRATORY TRACT, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose CONNECTIVE TISSUE, and an outer layer (muscularis mucosae) of SMOOTH MUSCLE CELLS that separates the mucosa from submucosa.	Lamina Propria,Mucosa,Mucosal Tissue,Muscularis Mucosae,Mucous Membranes,Membrane, Mucous,Membranes, Mucous,Mucosae, Muscularis,Mucosal Tissues,Propria, Lamina,Tissue, Mucosal,Tissues, Mucosal
D012007	Rectum	The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL.	Rectums
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000080908	Broadly Neutralizing Antibodies	Neutralizing antibodies that reduce or abolish some biological activity of a soluble antigen or infectious agent (e.g., HIV) by targeting several epitopes.	Broad Neutralizing Antibodies,Broad Neutralizing Antibody,Broad Spectrum Antibodies,Broadly Neutralizing Antibody,Cross-Neutralizing Antibodies,Cross-Neutralizing Antibody,bnAb,bnAbs,Antibodies, Broad Neutralizing,Antibodies, Broad Spectrum,Antibodies, Broadly Neutralizing,Antibodies, Cross-Neutralizing,Antibody, Broad Neutralizing,Antibody, Broadly Neutralizing,Antibody, Cross-Neutralizing,Cross Neutralizing Antibodies,Cross Neutralizing Antibody,Neutralizing Antibodies, Broad,Neutralizing Antibodies, Broadly,Neutralizing Antibody, Broad,Neutralizing Antibody, Broadly,Spectrum Antibodies, Broad
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D000911	Antibodies, Monoclonal	Antibodies produced by a single clone of cells.	Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal