Biodegradable Microrobots for DNA Vaccine Delivery.

The delivery of nucleic acid vaccine to stimulate host immune responses against Coronavirus disease 2019 shows promise. However, nucleic acid vaccines have drawbacks, including rapid clearance and poor cellular uptake, that limit their therapeutic potential. Microrobots can be engineered to sustain vaccine release and further control the interactions with immune cells that are vital for robust vaccination. Here, the 3D fabrication of biocompatible and biodegradable microrobots via the two-photon polymerization of gelatin methacryloyl (GelMA) and their proof-of-concept application for DNA vaccine delivery is reported. Programmed degradation and drug release by varying the local exposure dose in 3D laser lithography and further functionalized the GelMA microspheres with polyethyleneimine for DNA vaccine delivery to dendritic cell and primary cells is demonstrated. In mice, the DNA vaccine delivered by functionalized microspheres elicited fast, enhanced, and durable antigen expression, which may lead to prolonged protection. Furthermore, we demonstrated the maneuverability of microrobots by fabricating GelMA microspheres on magnetic skeletons. In conclusion, GelMA microrobots may provide an efficient vaccination strategy by controlling the expression duration of DNA vaccines.

Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong.

BACKGROUND: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated. METHODS: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people. FINDINGS: Standard BNT162b2 and CoronaVac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC50 and median frequencies of reactive CD4 subsets were consistently lower among CoronaVac-vaccinees than BNT162b2-vaccinees. CoronaVac did not induce measurable levels of nucleocapsid protein-specific IFN-γ+ CD4+ T or IFN-γ+ CD8+ T cells compared with unvaccinated. Against VOCs, NAb response rates and geometric mean IC50 titers against B.1.617.2 (Delta) and B.1.1.529 (Omicron) were significantly lower for CoronaVac (50%, 23.2 and 7.1%, <20) than BNT162b2 (94.1%, 131 and 58.8%, 35.0), respectively. Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among CoronaVac-vaccinees. INTERPRETATION: Our results indicate that vaccinees especially CoronaVac-vaccinees with significantly reduced NAbs may probably face higher risk to pandemic VOCs breakthrough infection. FUNDING: This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF and C1134-20GF); the Wellcome Trust (P86433); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.'s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

Association of body mass index with morbidity in patients hospitalised with COVID-19.

PURPOSE: To evaluate the association between body mass index (BMI) and clinical outcomes other than death in patients hospitalised and intubated with COVID-19. METHODS: This is a single-centre cohort study of adults with COVID-19 admitted to New York Presbyterian Hospital-Weill Cornell Medicine from 3 March 2020 through 15 May 2020. Baseline and outcome variables, as well as lab and ventilatory parameters, were generated for the admitted and intubated cohorts after stratifying by BMI category. Linear regression models were used for continuous, and logistic regression models were used for categorical outcomes. RESULTS: The study included 1337 admitted patients with a subset of 407 intubated patients. Among admitted patients, hospital length of stay (LOS) and home discharge was not significantly different across BMI categories independent of demographic characteristics and comorbidities. In the intubated cohort, there was no difference in in-hospital events and treatments, including renal replacement therapy, neuromuscular blockade and prone positioning. Ventilatory ratio was higher with increasing BMI on days 1, 3 and 7. There was no significant difference in ventilator free days (VFD) at 28 or 60 days, need for tracheostomy, hospital LOS, and discharge disposition based on BMI in the intubated cohort after adjustment. CONCLUSIONS: In our COVID-19 population, there was no association between obesity and morbidity outcomes, such as hospital LOS, home discharge or VFD. Further research is needed to clarify the mechanisms underlying the reported effects of BMI on outcomes, which may be population dependent.