ABSTRACT
Background. Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with increased transmissibility, disease severity, and resistance to neutralization by current vaccines under emergency use authorization (EUA). Here we assessed cross-immune responses of INO-4800 vaccinated subjects against SARS-CoV-2 VOCs. Methods. We used a SARS-CoV-2 IgG ELISA and a pseudo neutralization assay to assess humoral responses, and an IFNγ ELISpot to measure cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. Results. IgG binding titers were not impacted between wild-type (WT) and B.1.1.7 or B.1.351 variants. An average 1.9-fold reduction was observed for the P.1 variant in subjects tested at week 8 after receiving two doses of INO-4800 (Figure 1a). We performed a SARS-CoV-2 pseudovirus neutralization assay using sera collected from 13 subjects two weeks after administration of a third dose of either 0.5 mg, 1 mg, or 2 mg of INO-4800. Neutralization was detected against WT and the emerging variants in all samples tested. The mean ID50 titers for the WT, B.1.1.7, B.1.351 and P.1. were 643 (range: 70-729), 295 (range: 46-886), 105 (range: 25-309), and 664 (range: 25-2087), respectively. Compared to WT, there was a 2.1 and 6.9-fold reduction for B.1.1.7 and B.1.351, respectively, while there was no difference between WT and the P.1 variant (Figure 1b). Next, we compared cellular immune responses to WT and SARS-CoV-2 Spike variants elicited by INO-4800 vaccination. We observed similar cellular responses to WT (median = 82.2 IQR = 58.9-205.3), B.1.1.7 (79.4, IQR = 38.9- 179.7), B.1.351 (80, IQR = 40.0-208.6) and P.1 (78.3, IQR = 53.1-177.8) Spike peptides (Figure 2). Conclusion. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested.
ABSTRACT
Background. First-generation COVID-19 vaccines are matched to spike protein of the Wuhan-H1 (WT) strain. Convalescent and vaccinee samples show reduced neutralization of SARS-CoV-2 variants of concern (VOC). Next generation DNA vaccines could be matched to single variants or synthetically designed for broader coverage of multiple VOCs. Methods. The synthetic consensus (SynCon®) sequence for INO-4802 SARSCoV-2 spike with focused RBD changes and dual proline mutations was codon-optimized (Figure 1). Sequences for wild-type (pWT) and B.1.351 (pB.1.351) were similarly optimized. Immunogenicity was evaluated in BALB/c mice. Pre-clinical efficacy was assessed in the Syrian Hamster model. Figure 1. Design Strategy for INO-4802 Results. INO-4802 induced potent neutralizing antibody responses against WT, B.1.1.7, P.1, and B.1.351 VOC in a murine model. pWT vaccinated animals showed a 3-fold reduction in mean neutralizing ID50 for the B.1.351 pseudotyped virus. INO-4802 immunized animals had significantly higher (p = 0.0408) neutralizing capacity (mean ID50 816.16). ID50 of pB.1.351 serum was reduced 7-fold for B.1.1.7 and significantly lower (p = 0.0068) than INO-4802 (317.44). INO-4802 neutralized WT (548.28) comparable to pWT. INO-4802 also neutralized P.1 (1026.6) (Figure 2). pWT, pB.1.351 or INO-4802 induced similar T-cell responses against all variants. INO-4802 skewed towards a TH1-response. All hamsters vaccinated with INO-4802 or pB.1.351 were protected from weight loss after B.1.351 live virus challenge. 4/6 pWT immunized hamsters were completely protected. pWT immunized hamsters neutralized WT (1090) but not B.1.351 (39.16). INO-4802 neutralized both WT (672.2) and B.1.351 (1121) (Figure 3). We observed higher increase of binding titers following heterologous boost with INO-4802 (3.6 - 4.4 log2-fold change) than homologous boost with pWT (2.0 - 2.4 log2 fold change) (Figure 4). Conclusion. Vaccines matching single VOCs, like pB.1.351 and pWT, elicit responses against the matched antigen but have reduced cross-reactivity. Presenting a pan-SARS-CoV-2 approach, INO-4802 may offer substantial advantages in terms of cross-strain protection, reduced susceptibility to escape mutants and non-restricted geographical use.
ABSTRACT
COVID-19 first emerged in December 2019 in Wuhan, China, and has since spread throughout the world. More than one year has passed, and the virus continues to mutate and infect individuals at an increasingly alarming rate. Providing proper treatment to patients during the initial stages of the infection is highly vital for their survival. There is also a need for quicker testing. Such a situation demands an automated, easy-to-use COVID detection toolkit. Recent research using computer vision techniques suggests that chest X-rays contain essential features about the effects of the virus in the chest region. Advanced deep learning techniques and clinical imaging can be utilized to create a tool to detect COVID-19 and its severity. The proposed tool considers chest X-rays as well as a patient's symptoms to predict whether the patient has COVID or not and predict the severity for positive cases. © 2021 IEEE.
ABSTRACT
PURPOSE: Residency programs in the medical education field are considered the keystone in the development of aptitude and skills required for practice. With the worldwide current scenario of the COVID-19 pandemic, there has been a shift in the paradigm especially in the teaching of the residents from face-to-face classes to more and more online sessions. The purpose of this study is to present a compendium of knowledge-providing sites, smartphone applications (apps), YouTube channels, and podcasts that can provide better online resource management for students in the field of orthopaedics. METHODS: Search terms were used for making a list of various online resources which can be of help during orthopaedic residency. An initial list of the selected websites, smartphone apps, podcasts, and YouTube channels was made. The corresponding author with years of teaching experience and faculty for post-graduate and fellowship training programs then selected the final list. RESULTS: A list of 16 websites with brief points on their content and online address along with the availability of free or paid content was identified as being appropriate. A total of 39 apps available for android/apple smartphones, nine podcasts, and 11 YouTube channels were also identified as being extremely useful and have been discussed elaborately in this article. CONCLUSION: Online educational tools are of immense importance in imparting adequate knowledge to an orthopaedic resident and act as an adjunct to conventional teaching methods. This article focuses on presenting various online educational resources in a simple yet concise way, which may be beneficial for the current generation of residents especially in this current time of unprecedented COVID-19 pandemic.