Safety, immunogenicity and efficacy of an mRNA-based COVID-19 vaccine, GLB-COV2-043, in preclinical animal models.

Several COVID-19 vaccines, some more efficacious than others, are now available and deployed, including multiple mRNA- and viral vector-based vaccines. With the focus on creating cost-effective solutions that can reach the low- and medium- income world, GreenLight Biosciences has developed an mRNA vaccine candidate, GLB-COV2-043, encoding for the full-length SARS-CoV-2 Wuhan wild-type spike protein. In pre-clinical studies in mice, GLB-COV2-043 induced robust antigen-specific binding and virus-neutralizing antibody responses targeting homologous and heterologous SARS-CoV-2 variants and a TH1-biased immune response. Boosting mice with monovalent or bivalent mRNA-LNPs provided rapid recall and long-lasting neutralizing antibody titers, an increase in antibody avidity and breadth that was held over time and generation of antigen-specific memory B- and T- cells. In hamsters, vaccination with GLB-COV2-043 led to lower viral loads, reduced incidence of SARS-CoV-2-related microscopic findings in lungs, and protection against weight loss after heterologous challenge with Omicron BA.1 live virus. Altogether, these data indicate that GLB-COV2-043 mRNA-LNP vaccine candidate elicits robust protective humoral and cellular immune responses and establishes our mRNA-LNP platform for subsequent clinical evaluations.

"Reading" a new chapter in protozoan parasite transcriptional regulation.

Protozoan parasites continue to cause a significant health and economic burden worldwide. As infectious organisms, they pose unique and difficult challenges due to a level of conservation of critical eukaryotic cellular pathways with their hosts. Gene regulation has been pinpointed as an essential pathway with enough divergence to warrant investigation into therapeutically targeting. Examination of human parasites such as Plasmodium falciparum, Toxoplasma gondii, and kinetoplastids have revealed that epigenetic mechanisms play a key role in their gene regulation. The enzymes involved in adding and removing epigenetic posttranslational modifications (PTMs) have historically been the focus of study. However, the reader proteins that recognize and bind PTMs, initiating recruitment of chromatin-modifying and transcription complexes, are now being realized for their critical role in regulation and their potential as drug targets. In this review, we highlight the current knowledge on epigenetic reader proteins in model parasitic protozoa, focusing on the histone acyl- and methyl-reading domains. With this knowledge base, we compare differences between medically relevant parasites, discuss conceivable functions of these understudied proteins, indicate gaps in knowledge, and provide current progress in drug development.