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New Research: Paired SARS-CoV-2 spike protein mutations observed during ongoing SARS-CoV-2 viral transfer from humans to minks and Back to humans

The Elsevier journal of Infection, Genetics and Evolution published Flow Pharma’s Paper on the transfer of SARS-CoV-2 (COVID-19) between Minks and Humans (“zoonotic transfer”). Such transfers could cause problems for medical interventions, and our team showed it happening independently in Europe and the United States.

The Abstract is as follows:

A mutation analysis of SARS-CoV-2 genomes collected around the world sorted by sequence, date, geographic location, and species has revealed a large number of variants from the initial reference sequence in Wuhan. This analysis also reveals that humans infected with SARS-CoV-2 have infected mink populations in the Netherlands, Denmark, United States, and Canada. In these animals, a small set of mutations in the spike protein receptor binding domain (RBD), often occurring in specific combinations, has transferred back into humans. The viral genomic mutations in minks observed in the Netherlands and Denmark show the potential for new mutations on the SARS-CoV-2 spike protein RBD to be introduced into humans by zoonotic transfer. Our data suggests that close attention to viral transfer from humans to farm animals and pets will be required to prevent build-up of a viral reservoir for potential future zoonotic transfer.

Flow Pharma’s latest research was recently features on news-medical.net:

A new study describes a synthetic peptide used as a platform to generate protective adaptive cellular immunity to the virus in rhesus macaques, which are the gold standard for preclinical testing …

Our FLOVID-20 team released a new research preprint showing that Rhesus Monkeys vaccinated with FLOVID-20 were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 (COVID-19) infection and presented with lower viral loads relative to controls. It is submitted for peer review and publication.

Abstract

Background Persistent transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has given rise to a COVID-19 pandemic. Several vaccines, evoking protective spike antibody responses, conceived in 2020, are being deployed in mass public health vaccination programs. Recent data suggests, however, that as sequence variation in the spike genome accumulates, some vaccines may lose efficacy.

Methods Using a macaque model of SARS-CoV-2 infection, we tested the efficacy of a peptide-based vaccine targeting MHC Class I epitopes on the SARS-CoV-2 nucleocapsid protein. We administered biodegradable microspheres with synthetic peptides and adjuvants to rhesus macaques. Unvaccinated control and vaccinated macaques were challenged with 1 x 108 TCID50 units of SARS-CoV-2, followed by assessment of clinical symptoms, viral load, chest radiographs, sampling of peripheral blood and bronchoalveolar lavage (BAL) fluid for downstream analysis.

Results Vaccinated animals were free of pneumonia-like infiltrates characteristic of SARS-CoV-2 infection and presented with lower viral loads relative to controls. Gene expression in cells collected from BAL samples of vaccinated macaques revealed a unique signature associated with enhanced development of adaptive immune responses relative to control macaques.

Conclusions We demonstrate that a room temperature stable peptide vaccine based on known immunogenic HLA Class I bound CTL epitopes from the nucleocapsid protein can provide protection against SARS-CoV-2 infection in non-human primates.

The alarming trend in the number of observed mutations on SARS-COV-2, the virus causing COVID-19, continues apace. We continue to see mutations on these variants that could change the stability of the spike protein and its binding potential to antibodies, thus allowing for more infectivity and immune evasion respectively.

The number of mutated sequences and overall mutation count continues to increase as expected. This is cause for concern as sequence variants may not have the same efficacy as the previously characterized sequences against vaccines and therapeutics:

FLOVID-20 targets a subset of the nucleocapsid protein that has not been shown to mutate at a high degree. This region is conserved through evolution of coronaviruses due to its roles in replication of the viral genome. FLOVID-20 is able to accomplish this by specifically stimulating T-cells that can target these highly expressed and immunogenic conserved internal proteins. This is in stark contrast to current antibody vaccines and therapeutics that are restricted to targeting a region of the spike protein shown to mutate and evade antibodies in recent research.

The last few months have seen an alarming number of observed  mutations on SARS-COV-2, the virus causing COVID-19. These mutations may not be random, but increasing evidence points to viral variants avoiding protection given by vaccines, therapeutics, or previous infection:

“Some of the data I’ve seen in the last 48 hours have really scared me,” says Daniel Altmann, an immunologist at Imperial College London, who worries that some of results could portend a reduction in the effectiveness of COVID-19 vaccines.

“Fast-spreading COVID variant can elude immune responses”, Nature, Janurary 21, 2021

Mutations on these variants could change the stability of the spike protein and its binding potential to antibodies, thus allowing for more infectivity and immune evasion respectively.

The plot shown above illustrates the increasing mutations of spike protein around the time variants of the virus were discovered, specifically with origins in the United Kingdom, South Africa, and California. In January 2021, nearly 50% of viral samples sequenced from infected individuals around the world have been found to have 6 to 12 amino acid substitutions on the spike protein. The number of mutated sequences and overall mutation count is expected to continue to increase. This is cause for concern as sequence variants may not have the same efficacy as the previously characterized sequences against vaccines and therapeutics.

FLOVID-20 targets a subset of the nucleocapsid protein that has not been shown to mutate at a high degree. This region is conserved through evolution of coronaviruses due to its roles in replication of the viral genome. FLOVID-20 is able to accomplish this by specifically stimulating T-cells that can target these highly expressed and immunogenic conserved internal proteins. This is in stark contrast to current antibody vaccines and therapeutics that are restricted to targeting a region of the spike protein shown to mutate and evade antibodies in recent research.

Galveston National Laboratory
The Galveston National Laboratory (GNL) is a sophisticated high containment research facility that serves as a critically important resource in the global fight against infectious diseases.

Flow Pharma today announced that researchers at the University of Texas Medical Branch at Galveston (UTMB) will begin testing Flow Pharma’s FlowVax-based COVID-19 treatment candidate by challenging nonhuman primates with SARS-CoV-2, the virus that causes COVID-19 in humans, after the animals are vaccinated this month with FLOVID-20. FlowVax biomedicines utilize Flow Pharma’s patented Size Exclusion Antigen Presentation Control (SEAPAC(TM)) technology based on the benefits of making vaccine microspheres the same size as human white blood cells.