Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the "gold-standard" preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.

New method for objectively assessing lameness in broiler chickens.

A new method for assessing the severity of lameness in broiler chickens is described. The length of time that birds remained standing in shallow water was measured and the results were compared with the results of conventional gait scoring. There was a highly significant (P < 0.001) relationship between the birds' gait scores and their latency to lie down. Over 750 broilers aged between 32 and 45 days of age were tested in commercial houses and whereas nearly all the sound birds were able to stand for at least 15 minutes, the majority of lame birds lay down within five minutes.

A clinical comparison of subdural screw pressure measurements with ventricular pressure.

Simultaneous recordings of intracranial pressure (ICP) from a single-lumen subdural screw and a ventricular catheter were compared in 10 patients with severe head injury. Forty-one percent of the readings corresponded within the same 10 mm Hg ranges, while 13% of the screw pressure measurements were higher and 46% were lower than the associated ventricular catheter measurements. In 10 other patients, also with severe head injury, pressure measurements obtained with the Leeds-type screw were similarly compared with ventricular fluid pressure. Fifty-eight percent of the dual pressure readings corresponded, while 15% of the screw measurements were higher and 27% were lower than the ventricular fluid pressure, within 10-mm Hg ranges. It is concluded that subdural screws may give unreliable results, particularly by underestimating the occurrence of high ICP.