Abstract
Numerous studies continue to be published on the COVID-19 pandemic that is being caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Given the rapidly evolving global response to SARS-CoV-2, here we primarily review the leading COVID-19 vaccine strategies that are currently in PhaseIII clinical trials. Nonreplicating viral vector strategies, inactivated virus, recombinant protein subunit vaccines, and nucleic acid vaccine platforms are all being pursued in an effort to combat the infection. Preclinical and clinal trial results of these efforts are examined as well as the characteristics of each vaccine strategy from the humoral and cellular immune responses they stimulate, effects of any adjuvants used, and the potential risks associated with immunization such as antibody-dependent enhancement. A number of promising advancements have been made toward the development of multiple vaccine candidates. Preliminary data now emerging from phaseIII clinical trials show encouraging results for the protective efficacy and safety of at least 3 frontrunning candidates. There is hope that one or more will emerge as potent weapons to protect against SARS-CoV-2.
Highlights
The first cases of a viral pneumonia of unknown cause were reported in December 2019 in Wuhan, China (Huang et al 2020)
The virus spread across numerous borders, prompting the World Health Organization to declare a pandemic in March of
© The Author(s) or their Institution(s) progression. Another complication associated with SARS-CoV-2 is development of a “cytokine 2 storm” associated with severe COVID-19, causing acute respiratory distress syndrome (ARDS) likely due to, in part, a dysregulated 3 IFN-I response (Channappanavar et al 2016; Hadjadj et al 2020)
Summary
The first cases of a viral pneumonia of unknown cause were reported in December 2019 in Wuhan, China (Huang et al 2020). The majority of all nucleic acid, viral vector, and protein subunit vaccines produced and currently in development for SARS-CoV-2 work to elicit an immune response using these immunogens. In addition to inactivated whole virus vaccines as described below, isolated S protein can elicit non-neutralizing antibodies (nnAbs) from possible epitopes derived from it This may present a risk as it could potentially cause unwanted immune responses, such as antibody dependent enhancement (ADE) of disease (Jaume et al 2011; Wang et al 2014a) as discussed below. When developing a vaccine for SARS-CoV-2, it will be important to consider the possibility that mutations may arise in the future that could circumvent vaccine efficacy It has recently 2 been demonstrated that mutations in the RBD of the SARS-CoV-2 S-protein can be readily 3 selected for in the laboratory that enables the virus to evade monoclonal antibodies or 4 convalescent plasma (Weisblum et al 2020). This could preclude deployment of such vaccines in poorer 9 countries that may lack the infrastructure or resources to acquire and administer the vaccine
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