As the major vaccine target, the S protein has been evaluated in different types of vaccines against infection by CoVs [29]. Apart from the inactive whole virus particle [30], live attenuated virus with gene deletion [31] , four more vaccines which mainly contain S protein were studied. These include a virus-like particle which incorporated S protein into hepatitis virus or influenza virus protein [32,33]; virus vectors, such as modified vaccinia virus Ankara (MVA) or Adenovirus carrying S protein [34,35]; S protein subunit vaccine, like RBD-based protein [29,36]; and DNA vaccine which encodes the full length or part of the S protein gene [37,38]. Most of them have been tested in mouse models and showed the ability to elicit neutralizing antibodies. The first SARS-CoV DNA vaccine was tested in humans only 19 months after the virus sequence was published [38], while the DNA vaccine GLS-5300, the first MERS-CoV vaccine, went to clinical trials in 2016 [39]. In addition to these conventional vaccines, Liu et al. analyzed the T cell epitopes of SARS-CoV and MERS-CoV, revealed the potential cross-reactivity of the coronaviruses, and assessed the possibility of developing universal vaccines against coronavirus infections [40].