Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Commun. 2024 Nov 28;15(1):10332. doi: 10.1038/s41467-024-54580-9.
To prevent sexually-acquired HIV-1 infection by immunoprophylaxis, effective concentrations of broadly neutralizing antibodies are likely needed at mucosal sites of exposure. Here, we examine the biodistribution of monoclonal antibody VRC01 and its extended half-life variant, VRC01LS, in colorectal and genitourinary tracts of healthy adults 1-52 weeks after intravenous infusion. At 1-2 weeks, VRC01LS levels are ~3-4 times higher than VRC01 in serum (p = 0.048), rectal (p = 0.067), vaginal (p = 0.003) and cervical tissues (p = 0.003); these differences increase over time. Both antibodies primarily localize within rectal lamina propria and cervicovaginal stroma, with limited and variable epithelial distribution. Although 8-28% of serum mAb levels reach mucosal tissues, <3% are in seminal and rectal secretions. Elimination half-lives in mucosal tissues are 20-28 days for VRC01 and 51-68 days for VRC01LS. Thus, VRC01LS infusion achieves higher, sustained concentrations in human mucosal tissues than VRC01, supporting the future investigation of potent, long-acting LS-modified antibodies to prevent HIV-1.
为了通过免疫预防来防止性传播的 HIV-1 感染，在暴露于黏膜的部位，可能需要有效的广谱中和抗体浓度。在这里，我们研究了单克隆抗体 VRC01 及其延长半衰期变体 VRC01LS 在健康成年人静脉输注后 1-52 周的大肠和泌尿生殖道中的分布。在 1-2 周时，VRC01LS 的水平在血清（p=0.048）、直肠（p=0.067）、阴道（p=0.003）和宫颈组织中比 VRC01 高约 3-4 倍（p=0.003）；这些差异随着时间的推移而增加。两种抗体主要定位于直肠固有层和宫颈基质中，上皮分布有限且可变。尽管 8-28%的血清 mAb 水平到达黏膜组织，但只有<3%存在于精液和直肠分泌物中。VRC01 在黏膜组织中的消除半衰期为 20-28 天，VRC01LS 为 51-68 天。因此，VRC01LS 输注在人体黏膜组织中实现了更高、更持久的浓度，支持未来对强效、长效 LS 修饰抗体进行研究，以预防 HIV-1。
