Immunogenicity and Efficacy of Monovalent and Bivalent Formulations of a Virus-Like Particle Vaccine against SARS-CoV-2.

Virus-like particles (VLPs) offer great potential as a safe and effective vaccine platform against SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 VLPs can be generated by expression of the four viral structural proteins in a mammalian expression system. Immunization of mice with a monovalent VLP vaccine elicited a potent humoral response, showing neutralizing activity against multiple variants of SARS-CoV-2. Subsequent immunogenicity and efficacy studies were performed in the Golden Syrian hamster model, which closely resembles the pathology and progression of COVID-19 in humans. Hamsters immunized with a bivalent VLP vaccine were significantly protected from infection with the Beta or Delta variant of SARS-CoV-2. Vaccinated hamsters showed reduced viral load, shedding, replication, and pathology in the respiratory tract. Immunized hamsters also showed variable levels of cross-neutralizing activity against the Omicron variant. Overall, the VLP vaccine elicited robust protective efficacy against SARS-CoV-2. These promising results warrant further study of multivalent VLP vaccines in Phase I clinical trials in humans.

Ampicillin triggers the release of Pal in toxic vesicles from Escherichia coli.

In addition to lipopolysaccharides (LPS), outer membrane proteins - Lpp, OmpA and peptidoglycan-associated lipoprotein (Pal) - are part of the outer membrane of Escherichia coli and are proposed to contribute to bacterial sepsis-related inflammation. This study showed that ampicillin (a ß-lactam antibiotic) enhances Pal's release from Escherichia coli to a greater extent than gentamicin and levofloxacin (aminoglycoside and quinolone antibiotics, respectively). It is proposed that the majority of Pal is released in outer membrane vesicles (OMVs), which also contain LPS and other outer membrane and periplasmic proteins. The OMVs were purified by ultracentrifugation and characterised by transmission electron microscopy and nanoparticle tracking analysis, and Pal and other E. coli proteins were detected by Western blot. It also proposed that sepsis treatments using certain ß-lactam antibiotics may further aggravate the over-exuberant inflammatory response by enhancing the release of Pal and LPS in OMVs.

Comparing different maize supplementation strategies to improve resilience and resistance against gastrointestinal nematode infections in browsing goats.

The effect of maize grain supplementation on the resilience and resistance of browsing Criollo goat kids against gastrointestinal nematodes was evaluated. Five-month-old kids (n = 42), raised worm-free, were allocated to five groups: infected + not supplemented (I-NS; n = 10), infected + maize supplement at 108 g/d (I-S108; n = 8), maize supplement at 1% of body weight (BW) (I-S1%; n = 8), maize supplement at 1.5% BW (I-S1.5%; n = 8), or infected + supplemented (maize supplement 1.5% BW) + moxidectin (0.2 mg/kg BW subcutaneously every 28 d) (T-S1.5%; n = 8). Kids browsed daily (7 h) in a tropical forest for 112 days during the rainy season. Kids were weighed weekly to adjust supplementary feeding. Hematocrit (Ht), hemoglobin (Hb), and eggs per gram of feces were determined fortnightly. On day 112, five goat kids were slaughtered per group to determine worm burdens. Kids of the I-S1.5% group showed similar body-weight change, Ht and Hb, compared to kids without gastrointestinal nematodes (T-S1.5%), as well as lower eggs per gram of feces and Trichostrongylus colubriformis worm burden compared to the I-NS group (P > 0.05). Thus, among the supplement levels tested, increasing maize supplementation at 1.5% BW of kids was the best strategy to improve their resilience and resistance against natural gastrointestinal nematode infections under the conditions of forage from the tropical forest.