ABSTRACT
A "universal" platform that can rapidly generate multiplex vaccine candidates is critically needed to control pandemics. Using the severe acute respiratory syndrome coronavirus 2 as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates was engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers was found to be the most potent vaccine candidate in animal models. Without any adjuvant, this vaccine stimulated robust immune responses, both T helper cell 1 (TH1) and TH2 immunoglobulin G subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new nanovaccine design framework might allow the rapid deployment of effective adjuvant-free phage-based vaccines against any emerging pathogen in the future.
ABSTRACT
A "universal" vaccine design platform that can rapidly generate multiplex vaccine candidates is critically needed to control future pandemics. Here, using SARS-CoV-2 pandemic virus as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates were engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include: expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers is found to be the most potent vaccine candidate in mouse and rabbit models. Without any adjuvant, this vaccine stimulated robust immune responses, both T H 1 and T H 2 IgG subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new type of nanovaccine design framework might allow rapid deployment of effective phage-based vaccines against any emerging pathogen in the future.
ABSTRACT
AIM: Deficits in timing and sequencing behaviour in children with dyslexia and with attention-deficit hyperactivity disorder have already been identified. However many studies have not controlled for comorbidity between dyslexia and ADHD. This study investigated timing performance of children with either dyslexia or ADHD, or ADHD + dyslexia or unaffected children using a finger tapping paradigm. METHOD: Four groups of children (ADHD x Dyslexia) with a total of 68 children were compared using a four factorial design with two between-subject factors (ADHD (yes/no), dyslexia (yes/no)) and two within-subject factors, inter-stimulus interval (263, 500, 625, 750, 875 and 1000 ms) and tapping condition (free tapping, synchronous tapping, and unpaced tapping). In addition the complexity of rhythm reproduction pattern (unpaced tapping) was varied (simple/complex). RESULTS: No significant differences were found either in the ability of the ADHD or the dyslexia groups to sustain a self-chosen free tapping rate or to generate a stable inter-response interval either by synchronising to a signal or in reproducing a given interval without the previous pacing signal. Response averages showed the expected asynchrony and variability. In rhythm pattern reproduction the groups did not differ significantly in their ability to reproduce rhythms. However, a significant two way interaction effect between dyslexia and complexity was apparent indicating that the difference in levels of performance for simple versus complex rhythms was more pronounced for dyslexia than for the two other groups. CONCLUSION: The results indicate that motor timing ability in the millisecond range below 1000 ms in children with ADHD and/or dyslexia is intact. The performance of the comorbid group was revealed to be similar to the performance of the single disorder groups, but both the dyslexic groups were relatively worse than either the ADHD-only or the unimpaired group at reproducing complex versus simple rhythms.