A novel SARS-CoV-2 subunit vaccine engineered on an immune-activating platform technology.

While there are several SARS-CoV-2 vaccines currently available, additional options must be provided that are safe, effective, and affordable for the entire global population. We have developed a novel immune activating platform technology that will fill this need. This recombinant platform protein is produced in insect cells using baculoviral expression technology similar to what is currently used for several other approved vaccines as well as employed by myriad GMP facilities globally. Thus, infrastructure exists for rapid scale up following initial optimizations. Here we report initial results for a SARS-CoV-2 vaccine (OMN008) based on our platform technology. Unadjuvanted OMN008 vaccination resulted in robust antigenicity and neutralization. Additionally, OMN008 vaccination induced a specific CD8 T-cell response. All of these results taken together indicate OMN008 may be an excellent candidate to fill gaps left by the currently available vaccines. Further testing is necessary to fully optimize production; however, overall cost of production should remain low given the simple formulation of this recombinant platform.

Inhibition of Ras oncogenic activity by Ras protooncogenes.

Point mutations in ras genes have been found in a large number and wide variety of human tumors. These oncogenic Ras mutants are locked in an active GTP-bound state that leads to a constitutive and deregulated activation of Ras function. The dogma that ras oncogenes are dominant, whereby the mutation of a single allele in a cell will predispose the host cell to transformation regardless of the presence of the normal allele, is being challenged. We have seen that increasing amounts of Ras protooncogenes are able to inhibit the activity of the N-Ras oncogene in the activation of Elk in NIH 3T3 cells and in the formation of foci. We have been able to determine that the inhibitory effect is by competition between Ras protooncogenes and the N-Ras oncogene that occurs first at the effector level at the membranes, then at the processing level and lastly at the effector level in the cytosol. In addition, coexpression of the N-Ras protooncogene in thymic lymphomas induced by the N-Ras oncogene is associated with increased levels of p107, p130 and cyclin A and decreased levels of Rb. In the present report, we have shown that the N-Ras oncogene is not truly dominant over Ras protooncogenes and their competing activities might be depending on cellular context.

Human rgr: transforming activity and alteration in T-cell malignancies.

We have previously identified the oncogene rgr (ralGDS related) in DNA derived from a rabbit squamous cell carcinoma. Here we describe the identification of the human orthologue of the rabbit rgr gene termed hrgr (human ralGDS related). Four alternatively spliced full-length hrgr transcripts were isolated from normal human testes and liver libraries. Truncation of hrgr confers transforming ability to its cDNA. Using a RT-PCR assay we have been able to detect the expression of an abnormally truncated transcript in several human T-cell lymphoma lines, and in fresh tissue samples of patients with T-cell malignancies. In the DHL cell line, an Anaplastic Large Cell Lymphoma (ALCL) line, a DNA rearrangement was detected within the hrgr gene region. We propose that these T-cell lymphomas, at least in part, owe their malignant phenotypes to genetic alterations of the hrgr gene. These findings also raise the possibility that mutations in the hrgr gene are involved in other malignancies.