No abstract

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.

No abstract

Due to differences in human and murine angiotensin converting enzyme 2 (ACE-2) receptor, initially available SARS-CoV-2 isolates could not infect mice. Here we show that serial passaging of USA-WA1/2020 strain in mouse lungs results in “mouse-adapted” SARS-CoV-2 (MA-SARS-CoV-2) with mutations in S, M, and N genes, and a twelve-nucleotide insertion in the S gene. MA-SARS-CoV-2 infection causes mild disease, with more pronounced morbidity depending on genetic background and in aged and obese mice. Two mutations in the S gene associated with mouse adaptation (N501Y, H655Y) are present in SARS-CoV-2 variants of concern (VoCs). N501Y in the receptor binding domain of viruses of the B.1.1.7, B.1.351, P.1 and B.1.1.529 lineages (Alpha, Beta, Gamma and Omicron variants) is associated with high transmissibility and allows VoCs to infect wild type mice. We further show that S protein mutations of MA-SARS-CoV-2 do not affect neutralization efficiency by human convalescent and post vaccination sera.

Vertebral Body Tethering (VBT) is a non-fusion surgical treatment for Adolescent Idiopathic Scoliosis (AIS) that elicits correction via growth modulation in skeletally immature patients. VBT after peak height velocity is controversial and is the subject of this study. A retrospective review of Risser 3–5 AIS patients treated with VBT, and min. 2-year FU was performed. Pre to post-op changes in clinical outcomes were compared using Student’s t-test or the Mann-Whitney test. A total of 49 patients met criteria, age 15.0 ± 1.9 years, FU 32.5 ± 9.1 months. For thoracic (T) major curvatures, T curvature improved from 51.1 ± 6.9° to 27.2° ± 8.1° (p < 0.01) and TL from 37.2° ± 10.7° to 19.2° ± 6.8° (p < 0.01). For thoracolumbar (TL) major curvatures, T improved from 37.2° ± 10.7° to 18.8° ± 9.4° (p < 0.01) and TL from 49.0° ± 6.4° to 20.1° ± 8.5° (p < 0.01). Major curve inclinometer measurements and SRS-22 domains, except activity, improved significantly (p ≤ 0.05). At the latest FU, one (2%) patient required fusion of the T curve and revision of the TL tether due to curve progression in the previously uninstrumented T curve and tether breakage (TB) in the TL. Twenty (41%) patients experienced TB. VBT in AIS patients with limited remaining skeletal growth resulted in satisfactory clinical outcomes at the latest FU.