Shown in Table 1 is a summary of the major COVID-19 vaccines under development. This list is not exhaustive but instead reflects some of the major vaccines highlighted in company materials or publicly available documents, including biocentury.com [9].

Table 1 Major COVID-19 vaccine development programs Full size table

Whole Virus Vaccines

Live-attenuated or inactive whole virus vaccines represent a classic strategy for viral vaccinations. According to an industry newsletter, Johnson & Johnson is one of the few multinational companies embarking on COVID-19 vaccines [20]; similar to their Ebola vaccine platform, they are employing Janssen’s AdVac® adenoviral vector and manufacturing in their PER.C6® cell line technology [20, 21]. In addition, researchers at the University of Hong Kong have developed a live influenza vaccine that expresses SARS-CoV-2 proteins [22]. Finally, Codagenix has developed a “codon deoptimization” technology to attenuate viruses [23] and is exploring SARS-CoV-2 vaccine strategies. A major advantage of whole virus vaccines is their inherent immunogenicity and ability to stimulate toll-like receptors (TLRs) including TLR 3, TLR 7/8, and TLR 9. However, live virus vaccines often require extensive additional testing to confirm their safety. This is especially an issue for coronavirus vaccines, given the findings of increased infectivity following immunization with live or killed whole virus SARS coronavirus vaccines [7].

Subunit Vaccines

Subunit vaccines for both SARS coronaviruses rely on eliciting an immune response against the S-spike protein to prevent its docking with the host ACE2 receptor [7]. Already, under funding from the Coalition for Epidemic Preparedness (CEPI), the University of Queensland is synthesizing viral surface proteins, to present them more easily to the immune system. Moreover, Novavax has developed and produced immunogenic virus-like nanoparticles based on recombinant expression of the S-protein [24] while Clover Biopharmaceuticals is developing a subunit vaccine consisted of a trimerized SARS-CoV-2 S-protein using their patented Trimer-Tag® technology [14], although some full-length S-proteins for SARS also elicit increased infectivity and eosinophilic infiltration. Accordingly, a consortium led by Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine (including University of Texas Medical Branch and New York Blood Center) has developed and tested a subunit vaccine comprised of only the receptor-binding domain (RBD) of the SARS-CoV S-protein [7, 25, 26]. When formulated on alum, the SARS-CoV RBD vaccine elicits high levels of protective immunity on the homologous virus challenge. An advantage of the RBD-based vaccine is its ability to minimize host immunopotentiation [7]. Initial findings that the SARS-CoV and SARS-CoV-2 RBDs exhibit more than 80% amino acid similarity and bind to the same ACE2 receptor offer an opportunity to develop either protein as a subunit vaccine.

Nucleic Acid Vaccines

Several major biotechs have advanced nucleic acid vaccine platforms for COVID-19. For example, Inovio Pharmaceuticals is developing a DNA vaccine, while others, such as Moderna Therapeutics and Curevac, are exploring RNA vaccine platforms. The concept of immunizing with DNA began with promising results in mice in 1993 showing protective immunity against influenza, but for decades, these findings have not translated to similar findings in humans. More recently, new modifications and formulations have improved nucleic acid performance in humans, with an expectation that this approach might eventually lead to the first licensed human nucleic acid vaccine.