mRNA COVID-19 Vaccine(LiveRNA Therapeutics Inc.)

Immunization with messenger RNA (mRNA) or viral vectors encoding spike protein with diproline substitutions (S-2P) were shown to provide protective immunity, curbing the COVID-19 pandemic. However, in light of the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that can cause COVID-19, it is essential that we understand how immunization with spike protein elicits neutralizing antibodies (nAbs). Here, we compared immunization of macaques with mRNA vaccines expressing ancestral spike protein with or without diproline substitutions, showing that the diproline substitutions were not required for protection against SARS-CoV-2 challenge or induction of broadly neutralizing B cell lineages. One group of nAbs elicited by the ancestral spike protein lacking diproline substitutions targeted the outer face of the receptor binding domain (RBD), neutralized all tested SARS-CoV-2 VOC pseudotyped viruses including Omicron XBB.1.5 in vitro, but lacked cross-sarbecovirus neutralization. Structural analysis showed that the macaque nAbs that could broadly neutralize VOCs bound to the same epitope as a human nAb, DH1193. In contrast, vaccine-induced antibodies that targeted the RBD inner face neutralized multiple sarbecoviruses, protected mice from bat CoV RsSHC014 challenge, but lacked Omicron variant neutralization. Thus, ancestral SARS-CoV-2 spike mRNA vaccines lacking proline substitutions can induce B cell lineages binding to distinct RBD sites that either broadly neutralize animal and human sarbecoviruses or neutralize recent Omicron VOCs. Thus, the use of a nonstabilized spike protein design in some COVID-19 vaccines does not preclude the elicitation of broad sarbecovirus and broad VOC nAbs.

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.