SARS-CoV-2 Vaccine Targets: The Present and Future of COVID-19

Thu, 04/29/2021 - 17:48


Schematic of SARS-CoV-2 virus particle showing structural and non-structural proteins

Jamshed Arslan, Pharm D, PhD

Current approved and candidate vaccines

SARS-CoV-2 spike (S) protein is the main target of COVID-19 vaccines. Pfizer/BioNTech and Moderna vaccines are RNA-based vaccines while Oxford-AstraZeneca vaccine utilizes a non-replicating viral vector system to deliver SARS-CoV-2 DNA. Most of the candidate vaccines in clinical trials target spike protein subunits, but the danger of escape mutations is looming. Escape mutations refer to spike variants that escape vaccine targeting. When antibodies bind to the virus without neutralizing it, the Fc-region of the antibody interacts with the Fc-receptors on immune cells, like macrophages, resulting in viral uptake. The virus can then replicate inside the host cells, leading to immunopathology. One way to deter or circumvent escape strains has been to generate a polyclonal response by using a live-attenuated form of entire virus (measles, mumps, rubella, and others) or an inactivated virus (hepatitis A, rabies, and others). In fact, China’s Sinovac vaccine uses inactivated virus and is currently in Phase 4 trials. However, SARS-CoV-2 is capable of escaping neutralization even in the presence of polyclonal antibodies, as has been observed with convalescent plasma therapy from COVID-19 recovered patients.

Other strategies in clinical development include: using virus-like particles, that is, viral component(s) in a nanostructure lacking genetic material; and employing replicating or non-replicating viral vector with antigen-presenting cell, such as dendritic cell vaccine AV-COVID-19.

The number of vaccines in the pre-clinical phase is more than double that of vaccines in clinical trials. Some of the ingenious examples of diverse types of candidate vaccines are given below.


Simple Western lane view showing three negative samples (recombinant SARS-CoV-2 Spike S1 RBD protein, recombinant SARS-CoV-2 Spike S1 subunit protein, recombinant SARS-CoV-2 Spike S1/S2 subunit protein), and a positive recombinant SARS-CoV-2 Nucleocapsid protein sample with a specific band detected when probed with Rabbit Anti-SARS-CoV-2 Nucleocapsid Antibody.

 

Simple Western lane view shows three negative samples (recombinant SARS-CoV-2 Spike S1 RBD protein, recombinant SARS-CoV-2 Spike S1 subunit protein, recombinant SARS-CoV-2 Spike S1/S2 subunit protein), and recombinant SARS-CoV-2 Nucleocapsid protein. Specific bands were detected in the SARS-CoV-2 Nucleocapsid sample at approximately 60kDa using Rabbit Anti-SARS-CoV-2 Nucleocapsid Polyclonal Antibody (NBP3-00510).

 

 



Targeting multiple antigens by virus-like particles (VLPs) and cellular-based vaccines

At least two VLP vaccine platforms developed by Arizona State University are in the pre-clinical phase. One candidate vaccine employs the Myxoma virus that expresses parts of all four major structural proteins: spike, membrane (M), envelope (E), and nucleocapsid (N). Another approach is plasmid driven production of VLPs containing these proteins.

A unique cellular-based platform is also in the pre-clinical phase in which engineered human mesenchymal stem cells have been transfected with a plasmid expressing spike and N proteins. The purpose of these developments is to invoke both humoral and cellular immunity that can tackle escape strains.

 

Browse SARS Related Antibodies

 

Pan-coronavirus vaccine

Many coronaviruses like SARS, MERS, and SARS-CoV-2 can spill over from animals to humans. To stop the current and future epidemics related to coronaviruses, University of Cambridge with various collaborators is developing a DNA-vectored vaccine candidate DIOS-CoVax2. The researchers are conducting 3D computer modeling of the structures of SARS-CoV-2 and its evolutionary relatives (SARS, MERS). They are using banks of genetic sequences to target tiny fragments of viral structure crucial for binding with the human cells. In other words, the team is using synthetic genes that encode a plethora of antigen structures. These computer-generated custom-designed structures train the immune system (B- and T-cells) to target the crucial regions of the coronaviruses. By avoiding non-essential parts of viruses, the research team intends to avoid hyper-inflammatory responses.

These approaches must be taken with a grain of salt. The protection rate, safety, and immunogenicity of these novel strategies should be assessed through large-scale clinical trials. Only time will tell how effective and feasible these innovative strategies really are.


Dual RNAscope ISH-IHC of FFPE-tissue sections of SARS-CoV-2 infected human lung tissue probed for SARS-Cov-2 viral RNA (left) and anti-SARS Nucleocapsid Antibody (right) followed by anti-IgG HRP polymer antibody and DAB chromogen, then counterstained with hematoxylin (right).

Dual RNAscope ISH-IHC of formalin-fixed paraffin-embedded tissue sections of SARS-CoV-2 infected human lung tissue were probed for SARS-CoV-2 viral RNA (left) (anti-sense specific probe v-nCoV2019-S (ACD, 848561); Fast Red chromogen (ACD, 322360)). IHC tissue section (right) probed for rabbit polyclonal anti-SARS Nucleocapsid Antibody (NB100-56576) followed by incubation with anti-rabbit IgG VisUCyte HRP Polymer Antibody (VC003) and DAB chromogen (yellow-brown). Tissue was counterstained with hematoxylin (blue). Specific staining was localized to SARS-CoV-2 infected cells.


Jamshed ArslanJamshed Arslan, Pharm D, PhD   
Dr Arslan is an Assistant Professor at Salim Habib University (formerly, Barrett Hodgson University), Pakistan. His interest lies in neuropharmacology and preparing future pharmacists.

 

References

Dai, L., & Gao, G. F. (2021). Viral targets for vaccines against COVID-19Nature reviews. Immunology. https://doi.org/10.1038/s41577-020-00480-0.

Hope, J. L., & Bradley, L. M. (2021). Lessons in antiviral immunity. Science. https://doi.org/10.1126/science.abf6446.

Malik, J. A., Mulla, A. H., Farooqi, T., Pottoo, F. H., Anwar, S., & Rengasamy, K. (2021). Targets and strategies for vaccine development against SARS-CoV-2. Biomedicine & Pharmacotherapy. https://doi.org/10.1016/j.biopha.2021.111254.

Weisberg, S. P., Connors, T. J., Zhu, Y., Baldwin, M. R., Lin, W. H., Wontakal, S., Szabo, P. A., Wells, S. B., Dogra, P., Gray, J., Idzikowski, E., Stelitano, D., Bovier, F. T., Davis-Porada, J., Matsumoto, R., Poon, M., Chait, M., Mathieu, C., Horvat, B., Decimo, D., … Farber, D. L. (2021). Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum. Nature Immunology. https://doi.org/10.1038/s41590-020-00826-9

Williams, T. C., & Burgers, W. A. (2021). SARS-CoV-2 evolution and vaccines: Cause for concern? Lancet Respiratory Medicine. https://doi.org/10.1016/S2213-2600(21)00075-8.

World Health Organization. (2021, March 2). Draft landscape and tracker of COVID-19 candidate vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.


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