Overview of Vaccines Against Emerging Pathogenic Human Coronaviruses
Unlike the four low pathogenic human CoVs, including HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1, which cause mild to no pathogenesis in humans, SARS-CoV, MERS-CoV, and 2019-CoV are three highly pathogenic human CoVs (Channappanavar and Perlman, 2017; Cui et al., 2019; Zhu et al., 2020). With the increasing numbers of 2019-nCoV and MERS-CoV infections and continuous threat of re-emergence of SARS-CoV, as well as the potential of SARS- and MERS-related CoVs to cause human infections, it is critical to develop vaccines with strong efficacy and safety targeting these viruses to prevent their infections in humans. Since the vaccines against 2019-nCoV have not been available, the rest of the review will focus on the vaccines against SARS-CoV and MERS-CoV.
Although a variety of vaccines have been developed against SARS-CoV and MERS-CoV, most of them are in the preclinical studies, and only several have been tested in clinical trials4 ,5 (Du et al., 2016b; Cho et al., 2018). Nevertheless, no vaccines have been approved for the prevention of SARS and MERS in humans, demonstrating the need to develop effective and safe vaccines to control current MERS-CoV infection, or to be stockpiled for potential use against re-emerged SARS-CoV or SARSr-CoV. Particularly, effective and safe vaccines are urgently needed to prevent and control the current outbreak of 2019-nCoV.
Most SARS-CoV and MERS-CoV vaccines developed thus far are based on the inactivated or live attenuated viruses, DNAs, proteins, nanoparticles, viral vectors, including virus-like particles (VLPs) (Zeng et al., 2004; Jiang et al., 2005; Liu et al., 2005; Du et al., 2009a, 2016b; Pimentel et al., 2009; Al-Amri et al., 2017). Each vaccine type has different advantages and disadvantages. For instance, inactivated and live-attenuated virus-based vaccines are vaccine types developed using the most traditional approaches. Although they generally induce highly potent immune responses and/or protection, the possibility for incomplete inactivation of viruses or recovering virulence exists, resulting in significant safety concerns (Zhang et al., 2014). Also, these traditional vaccines may induce the antibody-dependent enhancement (ADE) effect, as in the case of SARS-CoV infection (Luo et al., 2018b). Similarly, some viral-vectored vaccines can elicit specific antibody and cellular immune responses with neutralizing activity and protection, but they might also induce anti-vector immunity or present pre-existing immunity, causing some harmful immune responses. Instead, DNA and nanoparticle vaccines maintain strong safety profile; however, the immunogenicity of these vaccines is usually lower than that of virus- or viral vector-based vaccines, often requiring optimization of sequences, components, or immunization routes, inclusion of appropriate adjuvants, or application of combinational immunization approaches (Zhang et al., 2014).