Phase I study of a non-S2P SARS-CoV-2 mRNA vaccine LVRNA009 in Chinese adults.

BACKGROUND: COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009). METHODS: In the single-centre, double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 µg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009. RESULTS: All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination. CONCLUSION: LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.

Safety and immunogenicity of hepatitis E vaccine in elderly people older than 65 years.

BACKGROUND: Hepatitis E virus (HEV) infection is a leading cause of acute hepatitis worldwide, and results in high morbidity and mortality rates among elderly people in China. The hepatitis E vaccine, Hecolin®, has been shown to be safe and highly efficacious among healthy adults aged 16-65 years old. However, there is no data about Hecolin® vaccination in elderly people older than 65 years (y). METHODS: An open-labeled, controlled trial was conducted to evaluate the safety and immunogenicity of Hecolin® among the elderly aged >65 y. A total of 601 eligible participants were enrolled. Among them, 200 elderly people aged >65 y and 201 adults aged 18-65 y were assigned to the Hecolin® groups and vaccinated at day 0, month 1 and month 6. Serum samples were collected for anti-HEV IgG determination at day 0 prior to immunization and at month 7. The remaining 200 elderly people aged >65 y were assigned to the safety control group and received no intervention but were instructed to report any adverse events that occurred during the whole study period in the same way as those in the Hecolin® groups. RESULTS: After receiving 3 doses of Hecolin® with the standard schedule, most (96.7%) of the vaccinated elderly people aged >65 y seroconverted at one month after the final dose (month 7). At month 7, the geometric mean concentrations of anti-HEV IgG were 5.36 (95% CI, 3.88-7.41) and 19.65 (95% CI, 16.81-22.98) among the baseline seronegative and seropositive elderly, respectively. Of the vaccinated elderly, 97.3% (177/182) had anti-HEV IgG levels higher than 1.0 WU/ml at month 7. Hecolin® was very well tolerated in this population. No vaccine-related SAEs were reported. CONCLUSIONS: Hecolin® is immunogenic and well tolerated in elderly people aged greater than 65 years.

Video-assisted thoracoscopic surgery lobectomy for lung cancer versus thoracotomy: a less decrease in sVEGFR2 level after surgery.

BACKGROUND: Angiogenic and anti-angiogenic factors play an important role in tumor biology and tumor recurrence after surgical resection. Antiangiogenic factors such as vascular endothelial growth factor (VEGF)-receptor 1 (sVEGFR1) and sVEGFR2, two soluble form receptor proteins of VEGF, are critical for angiogenesis. VEGF can be sequestered by soluble forms of these receptors, which result in decreasing VEGF amount available to bind to its receptor on vascular endothelial cell surface. This study aimed to investigate the influences of video-assisted thoracoscopic surgery (VATS) lobectomy and open by thoracotomy for early stage non-small cell lung cancer (NSCLC) on postoperative circulating sVEGFR1 and sVEGFR2 levels. METHODS: Forty-eight lung cancer patients underwent lobectomy through either VATS (n=26) or thoracotomy (n=22). Blood samples were collected from all patients preoperatively and postoperatively on days 1, 3 and 7. ELISA analysis was used to determine the plasma levels of sVEGFR1 and sVEGFR2. Data are reported as means and standard deviations, and were assessed with the Wilcoxon signed-Rank test (P<0.05). RESULTS: For all patients undergoing lobectomy, postoperative sVEGFR1 levels on days 1 and 3 were markedly increased, while postoperative sVEGFR2 levels on days 1 and 3 were significantly decreased. Moreover, VATS group had significantly higher plasma level of sVEGFR2 postoperative in comparison with open thoracotomy (OT) on day 1 (VATS 6,953±1,535 pg/mL; OT 5,874±1,328 pg/mL, P<0.05). CONCLUSIONS: Major pulmonary resection for early stage NSCLC resulted in the increased sVEGFR1 and decreased sVEGFR2 productions. VATS is associated with enhanced anti-angiogenic response with higher circulating sVEGFR2 levels compared with that with OT. Such differences in anti-angiogenic response may have an important effect on cancer biology and recurrence after surgery.

Effects of genistein and daidzein on the cell growth, cell cycle, and differentiation of human and murine melanoma cells(1).

Genistein and daidzein are two major isoflavonoids in dietary soybean that have inhibition effect on the cell growth of different tumor cell lines. We previously reported the anti-tumor activities of genistein and daidzein in human co1on tumor (HCT) cells and their different ability to enhance the activation of murine lymphocytes. In the present study, the effect of genistein and daidzein on the cell growth, cell cycle progression, and differentiation of murine K1735M2 and human WM451 cel1s was investigated. It was found that genistein could inhibit the cell growth of two metastatic melanoma cell lines, murine Kl735M2 and human WM45l in a dose-dependent manner. Flow cytometry showed that genistein could cause arrest of both Kl735M2 and WM45l at G(2)/M phase, while daidzein increased the cell numbers at S phase, decreased the cell numbers at G(1) phase. Detection of melanin and morphological observation showed that genistein can induce Kl735M2 and WM45l to produce dendrite-like structure and produce more melanin by 80%. In contrast, daidzein only retarded the growth of K1735M2 and did not induce differentiation in either K1735M2 or WM451. These results suggest that genistein and daidzein in soybean can inhibit certain malignant phenotype of melanoma via different mechanisms and be potential medical candidates for melanoma cancer therapy.