The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.

In this paper,the research progress of antibody-mediated targeting drug delivery system,including the targeting principal,efficiency,pharmacokinetics as well as pharmacodynamics of antibody drug conjugates,nanoparticles and liposomes,were summarized.Its feasibility and prospect in drug delivery system were analyzed.Antibody-mediated targeting drug delivery system not only improves the solubility of insoluble or poorly soluble drugs,but also accumulates the drug at targeted sites,increases the therapeutic effect of lesion and decreases toxicity.It can help for the development of kinds of targeted drug delivery system with high targeting efficiency,safety and economy.

This study investigated the use of a newly developed chitosan-Ca pectinate microbead formulation for the colon-targeted delivery of anti-A/B toxin immunoglobulin of egg yolk (IgY) to inhibit toxin binding to colon mucosa cells. The effect of the three components (pectinate, calcium chloride, and chitosan) used for the microbead production was examined with the aim of identifying the optimal levels to improve drug encapsulation efficiency, swelling ratio, and cumulative IgY release rate. The optimized IgY-loaded bead component was pectin 5% (w/v), CaCl2 3% (w/v), and chitosan 0.5% (w/v). Formulated beads were spherical with 1.2-mm diameter, and the drug loading was 45%. An in vitro release study revealed that chitosan-Ca pectinate microbeads inhibited IgY release in the upper gastrointestinal tract and significantly improved the site-specific release of IgY in the colon. An in vivo rat study demonstrated that 72.6% of biologically active IgY was released specifically in the colon. These results demonstrated that anti-A/B toxin IgY-loaded chitosan-Ca pectinate oral microbeads improved IgY release behavior in vivo, which could be used as an effective oral delivery platform for the biological treatment of Clostridium difficile infection (CDI).

A bifunctional RGDTAT peptide-modified PEG-PAMAM dendrimer conjugate RGDTAT-PEG-PAMAM (RTPP) was established for the targeted treatment of αvβ3-overexpressing tumor cells.

The incidence of Clostridium difficile infection has increased in Western world in the past 10 years, similar infection rates are also reported in developing countries such as China. Current antibiotics treatments have recurrence rates between 15% and 30%. IgY antibodies against toxin A of C. difficile could protect animal models from the challenge of lethal dose of C. difficile spores. However, IgY is sensitive to the low pH environment of the stomach and proteinases in the intestine. The objective of this study was to prepare colonic-specific delivery system of toxin A antigen-specific IgY to block the recognition of toxin A to the colon mucosa cells. Egg-laying hens were immunized with purified C. difficile toxin A C-terminal domain for 3 times, then egg IgY against the recombinant ToxA-C protein was purified from immunized egg yolk and frozen dried. IgY-loaded microbeads were prepared using mini fluid bed system; the loading efficiency was 21%. The pH and temperature stabilities of the microbeads were assayed. The IgY-loaded microbeads coated with 35% Eudragit S100 had colonic-specific IgY release specificity both in vitro and in vivo, the colonic-specific release of biological active IgY was 87.5% in the rat. Our study provides a new option for the biological treatment C. difficile infection.

Objective: To express carboxyl terminal of Clostridium difficile toxin B(TcdB-c) in E.coli and gener-ate chicken yolk antibodies(IgY) against TcdB-c. Methods: The gene sequence of TcdB-c was optimized and syn-thesized, and then it was cloned into pET32b(+) vector, followed by transformed into E.coli BL21(DE3) compe-tent cells. After induction, recombinant fusion protein was expressed and purified, and it was digested by thrombin to release TcdB-c. Biological activities of TcdB-c were assayed by hemagglutination and rabbit intestinal loop test. IgY antibodies against TcdB-c were generated from immunized egg laying hens, and specificity and activity of which were detected by ELASA and rabbit intestinal loop test respectively. Results: Recombinant protein with rela-tive molecular weight of 79 000 was solubly expressed in E.coli, and the released TcdB-c of 65 000 showed tox-ic effect on small intestine of rabbit. IgY antibodies specifically against TcdB-c had titer of 1∶20 000 and had neutralization activity. Conclusion: IgY antibodies against TcdB-c protein were prepared, laying foundation for the diagnosis and treatment of C.difficile associated diarrhea by gene engineering strategy.