Immunogen designs for COVID-19

(August 2020)

To ultimately stop the spread of the virus, we need an effective vaccine. 

There are a number of ongoing vaccine trials, and their goals are to raise neutralizing antibodies (nAbs) in people who receive the vaccine. The vaccine has to deliver immunogens (usually viral proteins but can be the genetic material of the immunogens as DNA or RNA) to activate the adaptive immune response to produce antibodies. Until efficacy can be demonstrated in the vaccine trials, the exact form of the immunogen that can lead to the production of nAbs is largely unknown.

The spike protein of SARS-CoV-2 virus is an attractive candidate, as it is the portion of the virus that is exposed to the environment and engages the ACE2 receptor for viral entry into the cell, so if antibodies can be raised to block its function, we would have an effective vaccine. However, a large portion of the spike protein is covered with glycans, which form the natural shield that the virus uses to evade the immune system, and the spike protein also has a number of variable loop regions that could be difficult to neutralize. While it is possible to create a vaccine with the wildtype spike protein, it is highly likely that we will need engineered variants of this protein – as subdomains, stabilized variants, etc. – to direct the immune response to its most vulnerable regions.

The Protein Design lab at Stanford Bioengineering, led by Professor Possu Huang, has extensive expertise in engineering protein immunogens. The lab has previous created a novel HIV vaccine platform, called eOD1, that is currently in clinical trials. We are developing new immunogens for COVID-19 to meet the urgent need to develop a COVID-19 vaccine. This work is conducted in collaboration with Prof. Rhiju Das. His group will take the immunogens designed in the Huang lab and use the crowdsourcing EteRNA platform2 to make the best sequences for their delivery as RNA vaccines.

Relevant Publications or More Information:

1.  Huang, P.-S., Jardine, J.G., Menis, S.V., Schief, W.R. & King, N.P. Engineered outer domain (eod) of HIV gp120 and mutants thereof. US Patent 10,421,789.
2.  Lee, J. et. al., RNA design rules from a massive open laboratory, Proceedings of the National Academy of Sciences, 111 (6) 2122-2127, 2014.