Biology subjects

Awasthi, M.

Publications and source records attributed to Awasthi, M..

3 recordsLinked to original sources

bioRxiv2023

Immunogenicity and Efficacy of TNX-1800, A Live Virus Recombinant Poxvirus Vaccine Candidate, Against SARS-CoV-2 Challenge in Nonhuman Primates

TNX-1800 is a synthetically derived live chimeric Horsepox Virus (rcHPXV) vaccine expressing Wuhan SARS-CoV-2 spike (S) protein. The primary objective of this study was to evaluate the immunogenicity and efficacy of TNX-1800 in two nonhuman primate species challenged with USA-WA1/2020 SARS-CoV-2. TNX-1800 vaccination was well tolerated, as indicated by the lack of serious adverse events or significant changes in clinical parameters. A single dose of TNX-1800 generated robust humoral responses in African Green Monkeys and Cynomolgus Macaques, as measured by the total binding anti-SARS-CoV-2 S IgG and neutralizing antibody titers against the USA-WA1/2020 strain. In Cynomolgus Macaques, a single dose of TNX-1800 induced a strong interferon-gamma (IFN-{gamma}) mediated T cell response, promoting both pathogen clearance in the upper and lower airways and generation of systemic neutralizing antibody response against WA strain SARS-CoV-2. Future studies will assess the efficacy of TNX-1800 against newly emerging variants and demonstrate its safety in humans.

immunology↗

bioRxiv2023

Immunogenicity and tolerability of a SARS-CoV-2 TNX-1800, a live recombinant poxvirus vaccine candidate, in Syrian Hamsters and New Zealand White Rabbits.

TNX-1800 is a preclinical stage synthetic derived live chimeric horsepox virus vaccine that comprises an engineered SARS-CoV-2 spike (S) gene expression cassette. The objectives of this study were to assess the immunogenicity and tolerability of TNX-1800 administration in Syrian golden hamsters and New Zealand white rabbits. Animals were vaccinated via percutaneous inoculation and evaluated for dose tolerance and immunogenicity at three different dose levels. The 28-day study data showed that the single percutaneous administration of three TNX-1800 vaccine dose levels was well tolerated in both hamsters and rabbits. For all dose levels, rabbits had more dermal observations than hamsters at the same dose levels. Vaccine-induced viral load four weeks post-dosing was below the detection level for both species.

immunology↗

bioRxiv2021

A cytoplasmic protein kinase in Chlamydomonas couples engagement of ciliary receptors to rapid cellular responses

The principal function of the primary cilium is to convert cues from the extracellular milieu into changes in cyclic nucleotide concentration and cytoplasmic responses, but fundamental questions remain about the mechanisms of transmission of cilium-to-cytoplasm signals. During fertilization in Chlamydomonas reinhardtii, ciliary adhesion between plus and minus gametes triggers an immediate [~]10-fold increase in cellular cAMP and activation for cell fusion. Here, we identify Gamete-Specific Protein Kinase (GSPK) as an essential link between cilary receptor engagement and gamete activation. The ciiary adhesion-induced increase in cAMP and cell fusion are severely impaired in gspk mutants but fusion is rescued by a cell-permeable form of cAMP, indicating that GSPK functions upstream of the cAMP increase. GSPK is cytoplasmic, and, remarkably, the entire cellular complement is phosphorylated in less than 60 seconds after ciliary contact. Thus, a cytoplasmic protein kinase rapidly converts a ciliary membrane cue into a global cellular response.

cell biology↗