mRNA COVID-19 Vaccine(LiveRNA Therapeutics Inc.)

The success of SARS-CoV-2 mRNA vaccines has boosted their development against various diseases, especially tumors. However, their clinical application is hindered by limited therapeutic efficacy and non-negligible side effects. Many studies attempt to improve therapeutic effect against tumors by using spleen-tropism mRNA delivery systems. Herein, we develop lipid nanoparticles (LNPs) based on hydroxychloroquine (HCQ)-derived ionizable lipid as a spleen-tropism mRNA delivery system that simultaneously modulates the tumor immune-suppressive microenvironment. The screened HCQ LNPs exhibit high mRNA transfection efficiency both in vitro and in vivo. Surprisingly, the HCQ LNP can achieve spleen-tropic transfection after systemic administration, which is conducive to immune cells for antigen presentation. In addition, HCQ LNP passively targeted to tumors significantly repolarizes tumor-associated macrophages to the M1 phenotype, thereby modulating the tumor microenvironment. Therefore, compared to the commercial MC-3 LNP/mOVA, HCQ LNP/mOVA shows significantly improved prophylactic and therapeutic antitumor efficacy and antimetastatic effect. HCQ LNP/mOVA demonstrates a multifaceted strategy that enhances the therapeutic efficacy of mRNA tumor vaccines through functional mRNA delivery system design.

In late 2019, the World Health Organization declared Coronavirus disease 2019 a global emergency. Since then, many vaccines have been developed to combat the pandemic. Millions of people have received one of the approved COVID-19 vaccines; unfortunately, some adverse events also have been recorded.

In the local health system, patients could get either mRNA vaccines (either Pfizer-BioNTech or Moderna), adenoviral vector vaccine (AstraZeneca), or the vaccine based on inactivated virus (Sinovac). We investigated what immune-mediated adverse events occurred in our department after the COVID-19 vaccination.

We evaluated six patients from our center who received mRNA vaccines and developed suspected immune-mediated adverse events. The immune-mediated adverse events are characterized by de novo or relapsing glomerular diseases and are further confirmed with percutaneous kidney biopsies. During A follow-up of more than two years, remission occurred in five patients, and glomerulonephritis persisted in one of them.

Vaccinations are pivotal in effectively protecting and preventing various epidemics. As such, it is essential to maintain a high level of vigilance concerning post-vaccination adverse events. This heightened level of suspicion leads to earlier detection, better understanding, and optimal prevention and management of these events. To this end, developing a specific vaccine/patient risk profile is necessary to categorize the target population selectively.