We previously developed a polysaccharide-–RBD-conjugated nanoparticle vaccine which induced protective efficacy against SARS-CoV-2 in a mouse model. Here, we newly developed a vaccine, SCTV01A, by chemically conjugating recombinant SARS-CoV-2 RBD-Fc and PPS14 (Streptococcus pneumoniae serotype type 14 capsular polysaccharide). The immunogenicity and toxicity of SCTV01A were evaluated in animal models. The PPS14 conjugation enhanced the immunogenicity of RBD-Fc in C57BL/6 mice whether formulated with SCT-VA02B or Alum adjuvant. SCTV01A also induced high opsonophagocytic activity (OPA) against S. pneumoniae serotype 14. In addition, SCTV01A stimulated potent neutralizing titers in rhesus macaques and effectively reduced lung inflammation after SARS-CoV-2 infection with neither antibody-dependent enhancement (ADE) nor vaccine-enhanced diseases (VED) phenomenon. Importantly, the long-term toxicity study of SCTV01A in rhesus macaques did not cause any abnormal toxicity and was tolerated at the highest tested dose (120 μg). The existing immunogenicity and toxicological evaluation results have demonstrated the safety and efficacy of SCTV01A, which will be a promising and feasible vaccine to protect against SARS-CoV-2 infection.

A new virus‐like particle based vaccine covering 14 types of high‐risk and disease‐inducing human papillomavirus (HPV) can offer better coverage against HPV‐induced diseases, particularly cervical cancers. However, the assessment of immunogenicity of the vaccine is an important task, representing not only its significant clinical characteristics, but also a major challenge, in terms of both the suitability of methods and the clinical sample testing throughput supporting clinical development. This work covers the development and evaluation of a method based on Luminex technology (a coded‐bead and flow‐cytometric approach) to assess the HPV‐type specific total immunoglobulin G (IgG). This method can evaluate the antibodies in sera post immunization against multiple types of HPV simultaneously (i.e., with multiplexing capability), save time and cost, and improve test throughput with higher sensitivity and precision than the classical, plate‐based enzyme‐linked immunoassay and competitive Luminex‐based immunoassays. Using cynomolgus monkeys as model, we demonstrated the good correlation between the results from the pseudovirion‐based neutralization assay (PBNA), and the Luminex‐based total IgG assay, supporting that the latter method can be considered as a viable, dependable replacement method for the PBNA supporting immunogenicity evaluation of HPV vaccine in preclinical development and clinical investigation.

Purpose Neutralizing antibodies, administrated through intravenous infusion, have shown to be highly efficacious in treating mild and moderate COVID-19 caused by SARS-CoV-2 infection in the lung. However, antibodies do not transport across the plasma-lung barrier efficiently, and up to 100 mg/kg dose was used in human causing significant supply and cost burdens. This study was to explore the feasibility of nebulized antibodies inhalation delivery as an alternative route. Methods HB27, a potent RBD-specific humanized monoclonal antibody (Zhu et al. in National Sci Rev. 8:nwaa297, 2020), showed excellent protection against SARS-CoV-2 in animal model and good safety profile in clinical studies. The pharmacokinetics and preliminary safety of HB27 administrated through the respiratory tract were studied in mice and cynomolgus monkeys here. Results At a single 5 mg/kg dose, the peak HB27 concentration in mice pulmonary epithelial lining fluid (ELF) reached 857.8 μg/mL, 670-fold higher than the PRNT90 value of 1.28 μg/mL, and maintained above PRNT90 over 240 h. In contrast, when administrated by intravenous injection at a 5 mg/kg dose, the antibody concentrations in mice ELF were below PRNT90 value throughout, and were about 50-fold lower than that in the serum. In cynomolgus monkeys administrated with a single dose through inhalation, the antibody concentration in ELF remained high within 3 days. No drug-related safety concerns were observed in the studies. Conclusions The study demonstrated that nebulized neutralizing antibody delivery though inhalation could be a more efficient and efficacious alternative approach for treating COVID-19 and other respiratory infectious diseases, and warrants further evaluation in clinical studies.

Background: The antibodies of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscapes for patients with cancer. Clinical uses of PD-1 antibodies have greatly improved the overall survival and durable responses in patients across selected tumor types. Methods: We describe the preclinical characterization of Finotonlimab, a humanized anti-PD-1 antibody, by head to head comparison with Nivolumab or Pembrolizumab. Herein, we characterized the in vitro and in vivo efficacy, PK, PD and Fc mediated effector function of Finotonlimab. The single-agent anti-tumor activity of Finotonlimab was evaluated using humanized mouse models and a human PBMC reconstituted mouse model. Furthermore, in cynomolgus monkeys, comparative PK measurements confirmed better PK profiles of Finotonlimab than that of Pembrolizumab and Nivolumab. Results: Our data showed Finotonlimab bind to human PD-1 with significantly high affinity and effectively inhibited its interaction with its ligands, PD-L1 and PD-L2, and thus could effectively stimulate the human T cell functions in vitro and exhibited significant antitumor efficacy in vivo. In addition, Finotonlimab showed minimal impact on Fc receptor dependent effector cell activation, which may contribute to the killing of PD-1+ T cells. In cynomolgus monkeys, Finotonlimab exhibited a non-linear pharmacokinetics (PK) profile in a dose-dependent manner, and approximately 90% of consistent receptor occupancy period was observed at 168 h after a single administration of 1 mg/kg. Following a 13-week successive administration of Finotonlimab, a pharmacodynamics study indicated a sustained mean receptor occupancy of ≥ 93% of PD-1 molecules on circulating T cells in cynomolgus monkeys up to 8 weeks even at 3 mg/kg. Conclusions: Taken together, these preclinical data are encouraging and provide a basis for the efficacy and pharmacodynamics of Finotonlimab in clinical trials.