Hosseinzadeh, R. | Search bioRxiv

bioRxiv2023

Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model

Maternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.

immunology↗

bioRxiv2020

SARS-CoV2 spike protein displays biologically significant similarities with paramyxovirus surface proteins; a bioinformatics study

Recent emergence of SARS-CoV2 and associated COVID-19 pandemic has posed a great challenge for the scientific community. Understanding various aspects of SARS-CoV2 biology, virulence and pathogenesis as well as determinants of immune response have become a global research priority. In this study, we performed bioinformatic analyses on SAR-CoV2 protein sequences, trying to unravel biologically important similarities between this newly emerged virus with other RNA viruses. Comparing the proteome of SARS-CoV2 with major positive and negative strand ssRNA viruses showed significant homologies between SARS-CoV2 spike protein with pathogenic paramyxovirus fusion proteins. This spike-fusion homology was not limited to SARS-CoV2 and it existed for some other pathogenic coronaviruses; nonetheless, SARS-CoV2 spike-fusion homology was orders of magnitude stronger than homologies observed for other known coronaviruses. Moreover, this homology did not seem to be a consequence of general ssRNA virus phylogenetic relations. We also explored potential immunological significance of this spike-fusion homology. Spike protein epitope analysis using experimentally verified data deposited in Immune Epitope Database (IEDB) revealed that the majority of spikes T cell epitopes as well as many B cell and MHC binding epitopes map within the spike-fusion homology region. Overall, our data indicate that there might be a relation between SARS-CoV2 and paramyxoviruses at the level of their surface proteins and this relation could be of crucial immunological importance.

bioinformatics↗