“Original Antigenic Sin”

This is part of series of posts by recipients of the 2020 Career Services Summer Funding Grant. We’ve asked funding recipients to reflect on their summer experiences and talk about the industries in which they spent their summer. You can read the entire series here.

This entry is by Nicole Tanenbaum, COL ’21

This summer, I continued working in the viral immunology lab I joined last fall.  I primarily worked on a project investigating why millennials were unusually impacted by this year’s influenza season.  It was hypothesized that this was due to a phenomenon called “original antigenic sin” where an individual’s first influenza virus exposure biases antibody responses to a a drifted, or mutated, strain of influenza later in life. Upon a secondary exposure, antibodies from the first exposure will be recalled, but they are not “tailored” to the mutated virus, resulting in an ineffective immune response.

Ironically, the current pandemic created some difficulties for conducting this virology research. Undergraduates were not allowed into Penn laboratories this summer, so I had to shift from pipetting at the bench to conducting research remotely. To address the question of whether millennials were exposed to virus early in life that differed from current strains, I relied on online databases and genomics tools.

I used an online database that contains influenza genome sequences from 1918 to the present. After downloading thousands of sequences, I aligned them using a tool called MEGA. I then wrote an R script that would go through sequences from each decade and determine the proportion of amino acids found at particular locations of the virus over time. I used a tool called Pymol to structurally depict where on the virus these mutations were located.

Interestingly, the viruses that circulated when millennials were children had amino acids that made them different from circulating viruses. Working with another lab member who could go to lab, I helped design and analyze results from experiments that tested whether antibodies from millennials could recognize the old virus, but not the new ones. Preliminary results suggest that this appears to be the case.

Although I wish I could have participated in this research in person, this was still a valuable experience. Not only did I gain valuable skills, but I got to engage in research that has clear applications. Given the current pandemic, research on viruses and their hosts is becoming increasingly important. Understanding how previous exposures to viruses shape antibody responses can prevent the development of an ineffective vaccine, or even inform how a more effective universal influenza vaccine could be formulated. With the prospect of future pandemics, this knowledge is critical for ensuring human health.

Thanks to summer funding from Career Services, I was able to pursue this opportunity. I am eager to continue researching this topic during the school year and in graduate school.

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