First Nerve-Related Immunoprobe for Guidance of Renal Denervation through Colocalization of NIR-II and Photoacoustic Bioimaging.

Nerve-related fluorophores generally locate in the visible or near-infrared region with shallow penetration depth and easy uptake by surrounding tissues. Prolonging the optical window promotes resolution by minimizing photoscattering and eliminating autofluorescence for NIR-II (second near infrared; 1000-1700 nm) and photoacoustic bioimaging. In addition, combination of the two could help in colocalization of targets at the 3D level. Catheter-based renal sympathetic denervation (RDN), an alternative treatment recently finishing its clinical evaluation for treating resistant hypertension, is highly dependent on experience and in urgent demand for in vivo guidance in locating the nerve over the renal artery. Here, an NIR-II and photoacoustic bioimaging system based on a dye-modified anti-tyrosine-hydroxylase antibody (TH-ICGM) to illustrate the peritoneal sympathetic nerve-related region are combined. With high resolution (0.15 mm) in NIR-II region for both absorbance (λex = 925 nm) and fluorescence (bioimaging in λem ≥ 1300 nm), TH-ICGM succeeds in providing 3D coordinates of procedure position with a precision in 0.1 mm. As the first nerve-related NIR-II immunoprobe, TH-ICGM has great clinical potential as assistance for nerve-related interventions.

Broad neutralization of SARS-CoV-2 variants by an inhalable bispecific single-domain antibody

The effectiveness of SARS-CoV-2 vaccines and therapeutic antibodies has been limited by the continuous emergence of viral variants, and by the restricted diffusion of antibodies from circulation into the sites of respiratory virus infection. Here, we report the identification of two highly conserved regions on Omicron variant RBD recognized by broadly neutralizing antibodies. Based on this finding, we generated a bispecific single-domain antibody that was able to simultaneously and synergistically bind these two regions on a single Omicron variant RBD as revealed by Cryo-EM structures. This inhalable antibody exhibited exquisite neutralization breadth and therapeutic efficacy in mouse models of SARS-CoV-2 infections. The structures also deciphered an uncommon cryptic epitope within the spike trimeric interface that may have implications for the design of broadly protective SARS-CoV-2 vaccines and therapeutics.