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

Publication ,  Journal Article
Astronomo, RD; Lemos, MP; Narpala, SR; Czartoski, J; Fleming, LB; Seaton, KE; Prabhakaran, M; Huang, Y; Lu, Y; Westerberg, K; Zhang, L ...
Published in: J Clin Invest
August 16, 2021

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.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

August 16, 2021

Volume

131

Issue

16

Location

United States

Related Subject Headings

  • Young Adult
  • Vagina
  • Rectum
  • Mucous Membrane
  • Middle Aged
  • Male
  • Infusions, Intravenous
  • In Vitro Techniques
  • Immunology
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Astronomo, R. D., Lemos, M. P., Narpala, S. R., Czartoski, J., Fleming, L. B., Seaton, K. E., … McElrath, M. J. (2021). Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. J Clin Invest, 131(16). https://doi.org/10.1172/JCI146975
Astronomo, Rena D., Maria P. Lemos, Sandeep R. Narpala, Julie Czartoski, Lamar Ballweber Fleming, Kelly E. Seaton, Madhu Prabhakaran, et al. “Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge.J Clin Invest 131, no. 16 (August 16, 2021). https://doi.org/10.1172/JCI146975.
Astronomo RD, Lemos MP, Narpala SR, Czartoski J, Fleming LB, Seaton KE, et al. Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. J Clin Invest. 2021 Aug 16;131(16).
Astronomo, Rena D., et al. “Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge.J Clin Invest, vol. 131, no. 16, Aug. 2021. Pubmed, doi:10.1172/JCI146975.
Astronomo RD, Lemos MP, Narpala SR, Czartoski J, Fleming LB, Seaton KE, Prabhakaran M, Huang Y, Lu Y, Westerberg K, Zhang L, Gross MK, Hural J, Tieu H-V, Baden LR, Hammer S, Frank I, Ochsenbauer C, Grunenberg N, Ledgerwood JE, Mayer K, Tomaras G, McDermott AB, McElrath MJ. Rectal tissue and vaginal tissue from intravenous VRC01 recipients show protection against ex vivo HIV-1 challenge. J Clin Invest. 2021 Aug 16;131(16).

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

August 16, 2021

Volume

131

Issue

16

Location

United States

Related Subject Headings

  • Young Adult
  • Vagina
  • Rectum
  • Mucous Membrane
  • Middle Aged
  • Male
  • Infusions, Intravenous
  • In Vitro Techniques
  • Immunology
  • Humans