Melanie McCauley, M.D.

Predicting patient responses to cancer immunotherapy

FUNDED: FEBRUARY 2018

FUNDED BY: The generosity of LJI Board Member Hunt Pettit and Laura Pettit

What was the goal of your SPARK project?

Dengue virus has circulated in tropical countries for decades. Now, the virus and its mosquito vector are moving into regions at higher elevations classically associated with cooler temperatures. This means millions more people are going to be at risk of this disease. As new populations of people become vulnerable to diseases like dengue virus for the first time, we have the opportunity to learn how a naïve immune system responds when an individual is first infected. In addition, we wanted to compare viruses from two separate climactic regions within Nepal to elucidate any genomic differences that may give dengue virus a selective advantage at cooler climate regions. Our goal was to gain valuable data on the immune system’s response to primary and secondary infection that could be used to design a safe vaccine for dengue.

SPARK project results:

In order to get started, it was crucial to bring much-needed supplies and training to our partners in Nepal so that we could strengthen our clinical research protocol and train new team members in experimental design and implementation to increase the accuracy and speed of our data collection. I used the SPARK funding to travel to Nepal for this critical stage and bring the much-needed supplies to make the sample collection a success. I was also able to purchase and supply our collaborators in Nepal with electronic tablets that can securely store patient data and allow our team at La Jolla Institute to keep track of the collection in real time. While there, I trained the team to use these tablets; discussed procedures for the year’s collection; and enrolled several patients who presented with suspected dengue illness in our study. One of the most important purchases the SPARK grant made possible was a temperature-controlled multipurpose centrifuge, which is critical to study human blood samples and preserve cell lines that are crucial to the study of the immune response to dengue virus infection. Another vital component to the study was providing access to very expensive diagnostic kits that help us look for dengue virus IgM antibody, IgG antibody and nonstructural protein 1 (NS1) antigens. SPARK funds allowed me to purchase enough kits to analyze banked samples from 2016 and 2017. These diagnostic studies allowed me to distinguish between patients who have no disease, a primary infection, or a secondary infection. We now know that 27 of our samples are positive for NS1, and from those we have isolated dengue virus and are planning to do full genome sequencing. Further analysis of samples collected in Nepal demonstrated that people in Nepal exhibit immunity to one or multiple serotypes of dengue virus, supporting our hypothesis that these viruses are more widespread in the country than previously observed. We did not find evidence of Zika virus infections.

What’s next for this project?

Information regarding circulating serotypes of both dengue and Zika virus give us valuable information regarding how the human immune response is shaped as viruses become endemic in a country, which could help several countries, including the United States, be better equipped to help protect people from these viruses. Currently, we still have several samples from the 2018 data collection season in Nepal that we plan to analyze once additional funding is secured for this project. My colleagues and principal investigator, Dr. Sujan Shresta, continue to seek grants and private funds to build on this data collected from this SPARK project and support our lab’s broader goal of developing a universal vaccine for dengue and Zika.

What’s next for Melanie?

I recently finished my infectious diseases fellowship at UC San Diego and La Jolla Institute and accepted a permanent position as a Research Physician with The Henry M. Jackson Foundation for the Advancement of Military Medicine supporting the Emerging Infectious Disease Branch at Walter Reed Army Institute of Research in Bethesda, M.D.. In this role, I will continue to study neglected tropical diseases in resource-poor countries, working to improve local capacity and infrastructure by conducting large-scale clinical trials.