Today I have the good fortune of bringing you an interview with my good friend Dr. Andrew Kilianski, who I have known for almost a decade. Dr. Kilianski is now Senior Director for Emerging Infectious Disease Vaccines at the International AIDS Vaccine Initiative (IAVI), which, as you will see, is one of the organizations developing a vaccine against the Ebola outbreak in Uganda.
What is IAVI?
IAVI is a nonprofit scientific research organization that develops vaccines and antibodies for HIV, tuberculosis, emerging infectious diseases (including COVID-19), and neglected diseases. Our mission is to translate scientific discoveries into affordable, globally accessible public health solutions.
We just had our 25th year anniversary, and while we have been focused on HIV/AIDS for most of that history, we have recently expanded the use of our global clinical network and laboratory infrastructure to also focus on emerging infectious diseases (EIDs). Our EID program is developing viral vectored-vaccines against Lassa virus (PhI in U.S. and Liberia), SARS-CoV-2 (an intranasal candidate which is moving towards clinical evaluation), Marburg virus, and Sudan virus. I lead our filovirus vaccine development programs with a focus on Marburg virus and Sudan virus.
How you decide what pathogens to work on?
IAVI works on infectious and neglected diseases. This is where our scientific expertise and our partnerships can make a significant contribution to protect people’s health globally. These include TB and certain neglected diseases and emerging infectious diseases, in addition to HIV/AIDS. Our guiding principles when deciding to work in an area are whether we bring added value and whether we can help achieve a significant impact on public health globally. As a coronavirologist, I believe that as climate changes and populations become more mobile, the global health community needs more quantitative ways to look forward at pathogens that might become greater health burdens in the future.
There are Ebola vaccines and therapeutics that were used in the 2014 West Africa outbreak and that are deployed regularly in DRC. Why won’t those work for this outbreak in Uganda?
The virus that caused the outbreak in 2014 is now called Ebola virus (genus ebolavirus, species zaire ebolavirus = ebolavirus zaire ebolavirus). The naming conventions of these viruses has changed since 2014 due to their distinct genetic composition, and those differences are why the vaccines and therapeutics developed against Ebola virus don’t work against Sudan virus (genus ebolavirus, species sudan ebolavirus = ebolavirus sudan ebolavirus). The main target of the vaccines and therapeutics developed against filoviruses are focused on their glycoprotein, which is a surface protein that binds to host-cell receptors (analogous to the SARS-CoV-2 spike protein). The glycoproteins of Ebola virus and Sudan virus are distinct enough that there isn’t cross protection against the viruses.
Tell us about the Ebola Sudan candidate your team is working on.
IAVI’s Ebola virus vaccine uses the VSV-vector platform to deliver the Sudan virus glycoprotein antigen and induces an antiviral response to generate anti-Sudan virus immunity. The VSV-vector platform is used in the licensed Ebola virus vaccine, ERVEBO®, developed by Merck. IAVI is also developing VSV-vectored vaccines that are in preclinical evaluation (VSV-SUDV, VSV-MARV, and VSV-SARS-CoV-2) and clinical trials (VSV-LASV). IAVI’s VSV-vectored vaccines use the same platform backbone as the licensed Ebola virus vaccine. In pre-clinical studies, the VSV-SUDV candidate induced protective immunity in non-human primates at multiple dose levels, and other published research replicates the results of IAVI’s studies. IAVI has also recently published results from a non-human primate efficacy study for VSV-MARV which demonstrated 100% efficacy in a wide range of doses. The VSV-SUDV candidate was developed in a research setting by the Public Health Agency of Canada, and IAVI retains a license to continue the development of this vaccine as a clinical candidate.
The candidate at IAVI is in the preclinical phase. What does it take to bring a candidate product all the way to clinic?
It takes a lot! Typically, a vaccine needs to be evaluated as safe and effective in non-human primates or other animal models, it needs to be manufactured in [high quality] manufacturing facilities, and in some cases biodistribution and toxicity studies might be needed. These activities all have to be done in accordance with a national pharmaceutical regulator, which in the U.S. is the FDA. A developer then has to file an investigational new drug application, which the FDA reviews, and then issues a “safe to proceed” if the product has been developed according to FDA standards. A similar process is used in other countries and by the European Medicines Agency. These processes allow a developer to enter a Phase I clinical trial, which is typically smaller in scope and is designed to determine if the vaccine or therapeutic is safe. Some data is also collected on the immunogenicity of the vaccines and how well they are inducing a productive immune response.
How long does that take in the best of times? How much can it accelerate in times of crisis?
From program start to a “safe to proceed” and the initiation of a Phase I study can take 3-5 years, sometimes longer. These timelines can be accelerated with dedicated preclinical resources and available manufacturing bandwidth (all done in parallel), similar to the approach taken by the U.S. in the development of the first-generation COVID-19 vaccines, but this approach induces risk as failures at any point in the preclinical development process would waste resources. IAVI’s VSV-SUDV program only started a year ago, but we have been greatly aided by 3 things:
- We have experience in developing VSV-vectored vaccines and getting them to the clinic. We have learned a lot along the way and have a robust partnership with a biomanufacturing partner, Batavia Biosciences, that allows for us to troubleshoot and plan strategically together. Investments made in our other VSV vaccines by CEPI and the Department of Defense continue to be realized in our new vaccine candidates due to the platform nature of our portfolio.
- Our VSV-SUDV program is funded by [U.S. government agency] BARDA, and they have been extremely flexible and helpful in our need to accelerate activities due to the outbreak in Uganda. Having a sponsor who is actively engaged and is there to help can greatly assist in the acceleration of a vaccine development program. Their experience in responding rapidly with medical countermeasures to EID outbreaks globally has been invaluable.
- IAVI has worked a lot with Merck in the past, including on our SARS-CoV-2 candidate, and we were fortunate to learn that Merck had retained bulk drug substance of a VSV-SUDV candidate they had developed with a license from Public Health Canada when their filovirus vaccine program was active. This bulk vaccine was on a stability plan and was stable, and Merck has donated vialed drug product to IAVI to accelerate our contribution to the outbreak response and the WHO ring trial setup in Uganda.
These factors—with Merck’s drug product donation being critical—have allowed for us to get a vaccine candidate that is ready for human trials in a year. It’s an incredible accomplishment and the team has done an amazing job! However, the road ahead is complicated, and we can’t take anything for granted just because we have drug product vialed.
What challenges do you see in the months ahead, as vaccine developers race to respond to the current outbreak?
The WHO has prioritized IAVI’s Sudan virus vaccine for entry into clinical trials in Uganda. Now the hard work begins as we have to work across international borders to ship material to Uganda and evaluate the safety, immunogenicity, and efficacy of the VSV-SUDV candidate in an outbreak environment. This adds a new layer to the already existing contract tracing and medical follow-up work being done by the Ugandan Ministry of Health. We’re fortunate to be working very closely with the WHO Research & Development team, who are leading the design, execution, and logistics of the clinical trials. They have a lot of experience in this area and IAVI’s team will be available to help where needed.
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