An oral vaccine for SARS-CoV-2 RBD mRNA-bovine milk-derived exosomes induces a neutralizing antibody response in vivo

The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) that causes the coronavirus disease 2019 (COVID-19) has presented numerous challenges to global health. The vaccines, including lipid-based nanoparticle mRNA, inactivated virus and recombined protein, have been used to prevent SARS-CoV-2 infections in clinics and are immensely helpful against the epidemic. Here, we first present an oral mRNA vaccine based on bovine milk-derived exosomes (milk-exos), which encodes the SARS-CoV-2 receptor binding domain (RBD) as an immunogen. The results indicated that RBD mRNA delivered by milk-derived exosomes can produce secreted RBD peptide in 293 cells in vitro and stimulated neutralizing antibodies against RBD in mice. These results indicated that bovine milk-derived exosome-based mRNA vaccine could serve as a new strategy for preventing SARS-CoV-2 infection. Meanwhile, it also can work as a new oral delivery system for mRNA. Keywords: bovine milk-derived exosomes; SARS-CoV-2; receptor binding domain; mRNA; oral vaccines; neutralizing antibody

Clinical investigation of sermn C-reactive protein and IL-18 in women with polycystic ovary syndrome and their relationship with isulin resistance / 中国综合临床

Objective To investigate the relationship of sermn C-reactive protein(CRP), IL-18 and insu-lin resistance(IR) in women with polycystic ovary syndrome (PCOS). Methods 36 women with PCOS (study group) and 20 healthy women (control group) were recruited. Serum C RP, IL-18 and sex hormone concentration were tested. Oral glucose tolerance tests (OGTT) and insulin release tests (IR) were conducted in all cases. Body mass index (BMI), fasting glucose to insulin ratio(FGIR), 2-hour glucose to insulin ratio(G120/I120) and homeo-markedly higher T level, LH/FSH ratio , logCRP and IL-18 than control group[(2.77±1.30) nmol/L vs (1.21±0.67) nmol/L, (2.31±0.87) vs (0.58±0.32), (0.16±0.20) vs (-0.47±0.38), (0.21±0.08) μg/L vs vs (22.23±2.68 ) kg/m2, P<0.05] and fasting insulin (I0) concentration [(35.76±24.11) mU/L vs (11.90± 5.32) mU/L, P<0.05)], higher serum glucose (G60=(9.77±2.75) mmol/L vs (7.84±2.02) mmol/L, G120= (7.97+2.07 ) mmol/L vs (6.24±1.80) mmol/L, P<0.05), insulin (I60= (228.38±60.16) mU/L vs (132.46±60.15) mU/L,I120= (172.94±48.39) mU/L vs (90.63±39.79) mU/L,P<0.05 for each) after OGTT and IRT than control group. HOMA-IR increased and FGIR decreased more significantly in study group than controls group (HOMA-IR=(9.59±4.72)vs (3.06±0.82), FGIR=(0.11±0.04) vs (0.23±0.02), HOMA-IR (r=0.5 and 0.37,P<0.05), IL-18 was positively correlatrd with BMI and HOMA-IR (r=0.58 and 0.61, P<0.05). Partial correlation showed that logCRP was positively correlated with HOMA-IR (r=0.46, P< 0.05), but negatively correlated with FGIR and G120/I120(r=-0.54 and -0.48,P<0.05 for all) in test group. Conclusion IR exists in women with PCOS, and their increased serum CRP and IL-18 level shows positive correla-tion with IR,demonstrating that chronic inflammation may participate in the pathogenesis of PCOS, and may have correlation with insulin resistance.