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MVA SARS-CoV-2 Vaccine Candidate Shows Strong Immunogenicity in Preclinical Studies

Modified vaccinia virus Ankara (MVA) is an attenuated vaccinia virus used as a vector for the already approved adenovirus-MVA-based Ebola vaccine.New preprint to appear in bioRxiv * The server is a preclinical recombinant MVA (rMVA) candidate vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the drug responsible for the current pandemic of coronavirus disease 2019 (COVID-19). I am reporting an exam. MVA provides a vector platform for the rapid production of such vaccines.

Current studies show the expression of SARS-CoV-2 virus full-length spike (S) glycoprotein antigen by rMVA. The rMVA spike-expressing virus showed efficient replication in the chicken embryonic fibroblast cell line DF-1, but not in the human cell line.

Antigen-antibody reaction in mouse

This has been demonstrated in mouse experiments to induce virus-specific antibodies. Both low and high doses (10)7 Or 108 The plaque formation unit (PFU)) was used for intramuscular vaccination. Following the first or first dose, certain IgG antibodies appeared in the sera of 3/8 and 4/6 animals in the low and high dose groups, respectively. By the 21st day after the second or booster immunization, all showed high IgG antibody titers.

These antibodies also bound to the S receptor binding domain (RBD) and were detected in 7/8 and 100% of low-dose and high-dose mice, respectively, after booster immunization.

Neutralizing antibodies were also detected in all serum samples after booster administration in two different assays: the plaque reduction neutralization test 50 (PRNT50) and the complete virus neutralization test (VNT50). These results were validated in a new high-throughput surrogate virus neutralization test for SARS CoV-2 (sVNT).

T cell response in mice

Researchers also found that vaccinated mice showed significant numbers of activated CD8 T cells after a single dose, both in the low-dose and high-dose groups. After booster administration, the magnitude of S-specific T cell activation increased. All activated cells expressed IFN-γ, and most also expressed TNF-α. Researchers also found activated CD4 T cells in both groups.

Protection against productive SARS-CoV-2 infection

The researchers then vaccinated the mice and then exposed the virus to the trachea two weeks after booster immunization. These mice were euthanized after 4 days. Control mice were found to be severely infected, but all immunized mice had significantly lower levels of SARS-CoV-2 RNA. Infectious virus was also detected at high levels in control mice, but not in vaccinated mice. This indicates that vaccinated mice developed an immune response that efficiently inhibited SARS-CoV-2 replication. The sera of these mice also contained certain neutralizing antibodies.

Implications

Researchers have used an MVA viral vector that replicates efficiently in DF-1 cells, making it suitable for rapid, large-scale commercial vaccine production. They used their previous experience with Middle East Respiratory Syndrome coronavirus (MERS-CoV) to design MVA and stably express full-length SARS-CoV-2 pedplomer when continuously amplified. I did.

The virus expresses the native S protein, which has been confirmed in all trait tests. Peplomers migrated through the Golgi apparatus of the host cell and localized on the cell surface. This suggests that MVA expresses mature, properly folded peplomer proteins.

Synthesis of full-length spike glycoprotein in MVA-SARS-2-S (MVA-S) infected cells. (A) Cells were infected with a multiplicity of infection of 0.5. MVA-infected cells acted as controls. Paraformaldehyde fixatives were either permeable or impermeable and were probed with a mouse monoclonal antibody against the HAtag or SARS-Cov-1 S protein (SARS-1-S). A polyclonal goat anti-mouse secondary antibody was used for S-specific fluorescence staining (red). Cell nuclei were counterstained with DAPI (blue).

Synthesis of full-length spike glycoprotein in MVA-SARS-2-S (MVA-S) infected cells. (A) Cells were infected with a multiplicity of infection of 0.5. MVA-infected cells acted as controls. Paraformaldehyde fixatives were either permeable or impermeable and were probed with a mouse monoclonal antibody against the HAtag or SARS-Cov-1 S protein (SARS-1-S). A polyclonal goat anti-mouse secondary antibody was used for S-specific fluorescence staining (red). Cell nuclei were counterstained with DAPI (blue).

This spike antigen has been shown to induce circulation-specific IgG antibodies that neutralize the virus in cell culture, as well as high levels of specific CD8 T cells. Neutralizing antibody titers were similar to those induced by current experimental vaccines.

The Prime Boost regimen has shown superior efficacy in line with Phase I clinical trials of the MVA MERS-S candidate vaccine previously developed by the same researchers. There were no signs of antibody-dependent enhancement of disease in vaccinated animals.

The strong T cell response seen after vaccination with this virus did not only indicate that this vaccine produces adaptive immunity. No infectious virus was recovered from the lung tissue of vaccinated animals in either the low or high dose group. This is important given many studies showing the importance of a strong cell-mediated immune response in COVID-19 recovery, and a strong CD4 or CD8 T cell response to SARS-CoV-2 is mild in such individuals. It is related to the disease.

Therefore, MVA-based SARS-CoV-2 spike expression candidate vaccines are safe and immunogenic in preclinical animal studies. Based on these results, the researchers began Phase I clinical trials on September 30, 2020. It is hoped that such vaccines will provide SARS-CoV with optimized immunity not only for CD4 and CD8 T cells, but for the entire spectrum of neutralizing activity. -Two infections in multiple population groups.

*Important Notices

bioRxiv publishes unpeer-reviewed preliminary scientific reports and should not be considered definitive, guide clinical / health-related behaviors, or be treated as established information.

MVA SARS-CoV-2 Vaccine Candidate Shows Strong Immunogenicity in Preclinical Studies

Source link MVA SARS-CoV-2 Vaccine Candidate Shows Strong Immunogenicity in Preclinical Studies

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