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1.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-506979

RESUMO

Mucosal vaccinations for respiratory pathogens provide superior protection as they stimulate localized cellular and humoral immunity at the site of infection. Currently, the major limitation of the intranasal vaccination is using effective adjuvants capable of withstanding the harsh environment imposed by the mucosa. Herein, we describe the efficacy of using a novel biopolymer, N-dihydrogalactochitosan (GC), as a nasal mucosal vaccine adjuvant against respiratory infections. Specifically, using COVID as an example, we mixed GC with recombinant SARS-CoV-2 trimeric spike (S) and nucleocapsid (NC) proteins to intranasally vaccinate K18-hACE2 transgenic mice, in comparison with Addavax (AV), an MF-59 equivalent. In contrast to AV, intranasal application of GC induces a robust, systemic antigen-specific antibody response and increases the number of T cells in the cervical lymph nodes. Moreover, GC+S+NC vaccinated animals were largely resistant to lethal SARS-CoV-2 challenge and experienced drastically reduced morbidity and mortality, with the animal weights and behavior returning to normal 22 days post infection. In contrast, animals intranasally vaccinated by AV+S+NC experienced severe weight loss, mortality, and respiratory distress, with none surviving beyond 6 days post infection. Our findings demonstrate that GC can serve as a potent mucosal vaccine adjuvant against SARS-CoV-2 and potentially other respiratory viruses.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-21250584

RESUMO

We describe the detection of SARS-CoV-2 (VOC)B.1.1.7 lineage in Oklahoma, USA. Various mutations in the S gene and ORF8 with similarity to the genome of B.1.1.7 lineage were detected in 4 of the 6 genomes sequenced and reported here. The sequences have been made available in GISAID. Presence of novel lineages indicate the need for frequent whole genome sequencing to better understand pathogen dynamics in different geographical locations.

3.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-20195420

RESUMO

Genomic sequencing has played a major role in understanding the pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the current pandemic, it is essential that SARS-CoV-2 viruses are sequenced regularly to determine mutations and genomic modifications in different geographical locations. In this study we sequenced SARS-CoV-2 from 5 clinical samples obtained in Oklahoma, USA during different time points of pandemic presence in the state. One sample from the initial days of the pandemic in the state and 4 during the peak in Oklahoma were sequenced. Previously reported mutations including D614G in S gene, P4715L in ORF1ab, S194L, R203K and G204R in N gene were identified in the genomes sequenced in this study. Possible novel mutations were also detected such as G1167V in S gene, A6269S and P3371S in ORF1ab, T28I in ORF7b, G96R in ORF8. Phylogenetic analysis of the genomes showed similarity to viruses from across the globe. These novel mutations and phylogenetic analysis emphasize the contagious nature of the virus.

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