By: Annalisa Torres, PharmD Candidate 2021; St. Louis College of Pharmacy at the University of Health Sciences and Pharmacy in St. Louis
Mentor: Paul Juang, PharmD, BCPS, BCCP, FASHP, FCCM; Professor, Department of Pharmacy Practice, St. Louis College of Pharmacy at the University of Health Sciences and Pharmacy in St. Louis
SARS-CoV-2 and COVID-19
As 2019 drew to a close, the world saw the emergence of a novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease known as Coronavirus disease 2019 (COVID-19). This highly pathogenic coronavirus was originally identified in Wuhan, China and would eventually spread to the rest of the global population resulting in a modern worldwide pandemic. The increased morbidity and mortality associated with COVID-19 resulted in the need for both the rapid manufacturing and global distribution of a safe and effective vaccine that is unparalleled.1 Due to its highly infectious nature that has resulted in numerous mortalities along with the global economic impact, understanding how SARS-CoV-2 enters the cell is an important factor in vaccine development.2
Like its predecessor, severe acute respiratory syndrome coronavirus (SARS-CoV), which resulted in the 2003 SARS outbreak, SARS-CoV-2, is a betacornoavirus that gains entry into the host cell via a spike protein (S2) that is present as a trimer on viral cell surfaces. A receptor binding domain for angiotensin-converting enzyme 2 (ACE2) is located on S protein resulting in the entry of both SARS-CoV and SARS-CoV-2 into the host cell. While the mechanism for entry is the same, slight variations in the receptor binding domain of SARS-CoV-2 result in a higher binding affinity for ACE2 compared to SARS-CoV.2 This mechanism has been the key area of interest related to COVID-19 vaccine development.3
Generally, it takes between 15 and 20 years before a safe and effective vaccine is available for distribution to the public.5,6 But given the need for more rapid vaccine development a public – private partnership known as Operation Warp Speed (OWS) was formed in May 2020. OWS is a partnership between the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector in order to accelerate not only vaccine development but also manufacturing and distribution, in the hopes of being able to provide at least 100 million doses by mid-2021.7
mRNA Vaccines: Moderna and Pfizer/BioNTech
A novel approach to vaccine development, messenger RNA (mRNA) based vaccines work on the notion that mRNA coded for pathogen antigen, in this case SARS-CoV-2, can not only be delivered to human cells but can then be used to produce antigen within the cell. mRNA vaccine technology synthesizes the viral protein by utilizing the human protein translational process. This method of vaccine delivery allows for a robust immune response without the introduction of live or inactivated portions of SARS-CoV-2. Due to its susceptibility to be rapidly degraded by ribonucleases, these vaccines need to be encapsulated with a lipid nanoparticle.5,6 Both Moderna in conjunction with NIAID (National Institute of Allergy and Infectious Disease) and Pfizer in conjunction with BioNTech have developed an mRNA based vaccine that encodes for spike protein found on the surface of SARS-CoV-2. 5,8,9
Adenovirus Vector Vaccines: AstraZeneca and Janssen
The vaccines currently being developed by AstraZeneca in conjunction with University of Oxford and Janssen Pharmaceuticals are known as replication-incompetent vectors. These vaccines have been engineered to express the spike protein found on SARS-CoV-2 while also disabling in vivo replication. Both vaccines are based on adenovirus vectors that deliver the spike protein to human cells. Upon entry into host cells, these vectors will allow for the expression of the spike protein, resulting in an immune response. While these vaccine types have been shown to elicit a good B and T cell response, they are somewhat affected by pre-existing vector immunity. In order to overcome this issue, vector types are either rare in humans, animal derived, or induce low immunity.5,6
Inactive Spike Protein Vaccines: Novavax and Sanofi/GlaxoSmithKline
The vaccine candidates being put forth by Novavax and Sanofi/GlaxoSmithKline utilize inactivated viral vectors to display the SARS-CoV-2 spike protein.5 The benefit of these vaccine types is that they are not only safe in immunocompromised individuals, and they have been extensively utilized in prior viral protein-based vaccines.6 NVX-CoV2373, the vaccine candidate from Novavax, includes the transmembrane domain of the wild-type SARS-CoV-2 spike (S) protein. As mentioned above, S mediates the attachment of SARS-CoV-2 to human cells.10
Table 1, comparing the current available data for the six leading COVID-19 vaccine candidates, is shown below.
Moderna. Moderna announces longer shelf life for its COVID-19 vaccine candidate at refrigerated temperatures. Moderna Web site. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-longer-shelf-life-its-covid-19-vaccine. November 16, 2020. Accessed November 17, 2020.
Word Health Organization. Draft landscape of COVID-19 candidate vaccines. Word Health Organization Web site. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. November 12, 2020. Accessed November 17, 2020.