Monkeypox virus quadrivalent mRNA vaccine induces immune response and protects against vaccinia virus.

Monkeypox has been declared a public health emergency by the World Health Organization. There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we develop two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two intracellular mature virus specific proteins (A29L and M1R) and two extracellular enveloped virus specific proteins (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice induce MPXV specific IgG antibodies and potent vaccinia virus (VACV) specific neutralizing antibodies. Further, it elicits efficient MPXV specific Th-1 biased cellular immunity, as well as durable effector memory T and germinal center B cell responses in mice. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP are protective against the VACV challenge in mice. And, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protects nude mice against the VACV challenge. Overall, our results demonstrate that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus.

Robust operation of distribution network based on photovoltaic/wind energy resources in condition of COVID-19 pandemic considering deterministic and probabilistic approaches.

In this paper, optimal allocation and planning of wind and photovoltaic energy resources are performed in a distribution network with the objective of reducing losses, improving reliability, and minimizing energy generation cost in terms of changes in load consumption pattern during the COVID-19 pandemic condition. The main goal is identifying the best operating point, ie the optimal location and size of clean energy resources in the worst load change conditions, which ensures the best network operation in all conditions during the COVID-19 condition via the turbulent flow of water-based optimization (TFWO). First, the deterministic approach is implemented in Hybrid and Distributed cases before and during COVID-19 conditions. The probabilistic approach is performed considering generation uncertainty during the COVID-19 conditions. The results showed better performance in the Distributed case with the lowest losses and higher reliability improvement. Moreover, the losses are significantly reduced and the reliability is improved during the COVID-19 pandemic conditions. The findings indicate that the allocation and planning during the COVID-19 conditions is a robust option in network operating point changes. Also, the probabilistic results showed that considering the uncertainty has increased active and reactive losses (4.67% and 5.82%) and weakened the reliability (10.26%) of the deterministic approach.

Self-assembled polymeric micelle as a novel mRNA delivery carrier.

mRNA-based therapy has been evaluated in preclinical and clinical studies for the treatment of a wide variety of disease such as cancer immunotherapies and infectious disease vaccines. However, it remains challenging to development safe and efficient delivery system. Here, we have designed a novel self-assembled polymeric micelle based on vitamin E succinate modified polyethyleneimine copolymer (PVES) to delivery mRNA. In vitro, PVES could transfect mRNA into multiple cell lines such as HEK-293T, HeLa and Vero and the transfection efficiencies were much higher than PEI 25 k. In addition, the cytotoxicity of PVES was much lower than PEI 25 k. Furthermore, mice administered intramuscularly with PVES/SARS-CoV-2 mRNA vaccine induced potent antibody response and show no obvious toxicity. These results demonstrated the potential of PVES as a safe and effective delivery carrier for mRNA.