The Peter Kim Lab searches for an all-in-one filovirus vaccine

On Oct. 6, the Coalition for Epidemic Preparedness (CEPI) awarded the Peter Kim Lab $18 million to create a single, effective vaccine that protects against a broad range of filoviruses, including known Ebola strains, Marburg virus and future viruses. Peter Kim Ph.D. ’85 and his team are utilizing AI tools and over 25 years of research from prior Peter Kim Lab members to make this possible. 

Currently, there are two FDA-approved vaccines that prevent Ebola Zaire, a specific strain of Ebola that has caused 25-90% fatality rates in past outbreaks. However, Kim said that many companies have no financial incentive to create vaccines for those in Central Africa most likely to be affected by Ebola. As a result, no effective vaccine has been created to protect against all three known strains of Ebola, Marburg virus and various other filoviruses, he said. 

This is where Kim and his team, specifically Rebekah Costello, a third-year Ph.D. candidate in immunology, and Varun Shanker, a fourth year M.D.-Ph.D. candidate in biophysics, are looking to make a difference.

Most vaccines, including common flu vaccines and the Ebola Zaire vaccine, use a weakened live virus to stimulate the immune system to create antibodies to prevent future attacks. These live viruses, however, require storage temperatures of -80 °C, making them inaccessible to people all around Central Africa. Kim’s group aims to rectify this gap. 

“We’re looking to create a vaccine that doesn’t require low-temperature storage and that’s cheap to make. And it’s effective. And it does something that nobody’s done before, which is to cover all these filoviruses,” Kim said. 

The Kim Lab, however, has previously achieved a similar goal. At the start of the COVID-19 pandemic, they shifted their research focus towards developing a COVID-19 vaccine in order to continue receiving funding. In order to make a cheap, effective vaccine that was stable at room temperature, they created a protein-based — as opposed to live virus — vaccine. Specifically, they isolated the spikes that extruded out of a protein and injected them into the body to stimulate an immune response. 

“Peter has had a long-standing interest in Ebola since the 1990s. He won’t tell you himself, but he was the first person to solve the structure of the Ebola fusion protein,” Shanker said. 

Through the use of an adjuvant, a substance that increases the immune response of a vaccine, and by attaching these protein spikes to a ferritin nanoparticle, the vaccine met all the criteria. It was incredibly effective across all COVID-19 strains — alpha, beta and omicron — because it had enough immune response to neutralize all pathogenic threats. 

Although Kim himself wasn’t able to come into the lab during the COVID-19 crisis, he praises previous members, including Abigail Powell, a former postdoctoral researcher under Kim, for her pivotal work in engineering the COVID-19 vaccine. Post-COVID, Duo Xu, another former postdoctoral researcher under Kim, took Powell’s methods and implemented them into an Ebola vaccine. He added another step, which included shielding the protein spikes that were variable — protecting for the differences in strains of Ebola — through glycoproteins, or long sugars on the surface of the protein. 

That’s where CEPI comes in. CEPI is a global partnership launched in 2017 to fund and coordinate the development of vaccines against emerging infectious diseases — especially those that could cause epidemics or pandemics. CEPI was founded by the governments of Norway and India, the Bill & Melinda Gates Foundation, the Wellcome Trust and the World Economic Forum.

“CEPI’s goal is to create effective methods of rapid response in the case of an outbreak of a novel pathogen. Our goal, in conversation with CEPI, is to create a vaccine that protects against filoviruses we don’t even know about yet,” Costello said.

The Peter Kim Lab approached CEPI with advancements to make the process more effective. 

“One of the main thrusts of the lab has been using AI and ML to accelerate [the] process,” Shanker said. 

He utilizes language learning models to optimize protein code and sugar shielding structure, in order to keep the vaccine protein stable and effective over many strains of pathogens.

The plan, then, will be to vaccine candidates using these new methods and then test them against 11 different filoviruses.

The post The Peter Kim Lab searches for an all-in-one filovirus vaccine appeared first on The Stanford Daily.