Research scientist working on vaccine development
(Long Beach, CA)
Jenny Hernandez and I were AP (Advanced Placement) Biology class lab mates when I was a sophomore and she a junior. I remember us being a great team. Our teacher chose and took a handful of us from class to go to Los Angeles Chiropractic College to observe, touch and feel dissected human cadavers and Jenny and I shared the truly eye-opening experience together. It had been several years since we saw each other. When I pulled up to University of California, Irvine medical school parking lot, Jenny came on foot to pick me up and escort me to her lab. Her bright and genuine smile was as sunny as the early afternoon sky in Southern California.
Jenny gave me a short tour around the lab and introduced me to her colleagues. She tried to explain some of the complex biology lab processes that went on there and I didn’t understand most of what she said, at least not the first time. It reminded me how my biology education ended with the class we took together whereas she went onto receiving her PhD in it. I felt nostalgic reminiscing about studying and dissecting with her and also envious about and awed by her expertise in her field.
Hazel: Jenny, thank you so much for letting me come visit you and spending time with me. It’s so great to see you! Nice to come to the vaccine research center to learn about how a flu vaccine gets developed.
Jenny: It’s my pleasure, Hazel. It’s great to see you.
Hazel: You just showed me the incubator where you grow canine kidney cells (MDCK) which will be eventually used to grow the flu virus. Can you tell me why you choose those cells in particular?
Jenny: MDCK cells have sugars (sialosides) on their surface arranged in a particular conformation called α2-3-linked (for avian-like) or α2-6-linked (human-like) that the flu virus uses to recognize, attach to and infect cells. These are the same ones found on the surface of nasal epithelial cells. These cells have been characterized to grow influenza virus well. Not all cells have the surface conducive to viral infection. Liver cells, for example, do not have the same receptors and the virus doesn’t infect them, so the liver cells are not ideal for growing virus.
By far, the best growth of virus occurs in eggs and eggs are used to grow current flu vaccines. Unfortunately, we don’t have the resources available to us yet to grow virus in eggs.
Hazel: Is this why when we get the flu, our respiratory system gets affected a lot?
Jenny: Yes. The flu virus can infect human nasal epithelial cells containing these receptors and “hijacks” the cell’s machinery to produce more virus. Each virus has a specific target. The influenza virus (flu) has these particular receptors it binds to. A virus like the current Coronavirus targets receptors (ACE2) in the lungs with really high affinity causing massive inflammation and pneumonia like symptoms in the lungs. A virus as HIV targets T-cells, the cells of the immune system.
Hazel: The canine kidney cells seem to be in a liquid form. What kind of preparation was done to make them to be in that state? What setting does incubator have to be in?
Jenny: The cells themselves are not liquid, but they require nutrient media with certain amino acids, sugars, and minerals required for the cell to live. That’s why you see this “kool-aid” like liquid. The cells adhere to the plate and this liquid media is used to keep them alive. We put them in a specialized incubator. The purpose of the incubator is to mimic the natural cell environment. That setting is achieved by establishing the temperature at 37 degrees Celsius, CO2 level of 5%, and humidity level at 95%.
Hazel: Then, what do you do with these cells?
Jenny: We use these cells for a variety of our studies. First, we grow them and add virus to them and allow them to be infected. About 3 days later, we look at the media and the media should have produced tons of virus by then. It’s obvious when the virus grows on cells because the cells start to look quite sick by being shriveled and distressed. We collect the infected cells and media and use the centrifuge to separate out the cells from the virus. We freeze the extracted virus for future usage.
We also use the canine kidney cells to measure the concentration of virus, or the potency of it. We can also test if antibodies produced by mice immunized by our vaccines are effective to neutralize it, if it does at all.
Hazel: How do you test the vaccine’s effectiveness against the virus?
Jenny: We immunize our mice with our vaccine cocktail, formulation. Then, we draw blood and spin down the blood in centrifuge to remove blood clotting agent and extract only the serum component. We use the serum to incubate it with the virus. If the formulation is effective, or the antibodies are able to “neutralize” the virus the blood cells should be protected from the virus and we should not see infection. Alternatively, we can do protection studies by first immunizing mice and note their ability to survive after a period of time.. If they do survive longer than non-immunized mice, we may be able to conclude that the vaccine is effective. When we prove that the formulation is effective, we publish our results and hope that pharmaceutical companies will use this to put the vaccine through clinical studies, which can take many years. The studies can be quite long and extensive, so it may be a while before a vaccine is used in the public. A lot of these time delays are currently being waived today in the production of the coronavirus vaccine.
Hazel: How do you create vaccine against the virus?
Jenny: We use the proteins that are found on the surface of the virus to create a vaccine. In the case of influenza, the main “anchor” that binds the cells is a surface protein on the virus called Hemagglutinin (HA). We use HA proteins from a wide variety of strains to make our vaccines. We hope that by allowing antibodies made to this “anchoring” protein, the cells will be protected from being infected. In the case of Coronavirus, the spike protein usually binds the surface of ACE2 receptor on lung cells. Often vaccines will be made against this protein. Sometimes it will be a cocktail of all viral proteins.
Hazel: Why do you create protein-based vaccines instead of the live attenuated virus kind as you used to?
Jenny: Protein-based vaccines are much less likely to make individuals feel ill when we they get vaccinated, as they don’t trigger the immune response as massively as the live attenuated viruses do. By having milder symptoms after vaccination, people may be more encouraged to be vaccinated, which is a problem currently. Also, with protein-based vaccines, we can target multiple proteins from the virus or from a variety of strains with one injection. The science community is hoping to achieve universal vaccine where a vaccine can block all strains of influenza viruses from binding to our cells.
Hazel: So how do you determine which strains of virus to grow?
Jenny: Our lab is trying to create a vaccine that will be good against all different strains of the flu virus, H1N1, H3N2, H5N1, H7N9, etc… We simply buy these viruses from vendors and use those for testing with our vaccine. Our current vaccines usually only use a combination of H1N1, H3N2 and influenza B viruses to protect. If we don’t predict the right strains to include in our vaccine, then the vaccine is not as effective that year. We are trying to change that by creating one that will protect against any of those strains that may appear in circulation. I don’t know if you recall the H5N1 pandemic from years back. It was scary because most people don’t have antibodies against H5N1. Our hope is that if there was another H5N1 pandemic, we would hope to provide cross protection. Vaccines, in general, take several months to mass produce, not to mention time for testing. It’s often hard to predict what strains will be in circulation at the time. During the vaccine production time, the relevant strains of influenza can change.
Hazel: How fascinating! If I remember correctly, I thought you were a cancer biologist. How did you come to research vaccines?
Jenny: I actually worked in this lab right after getting my bachelor’s degree. I came to this lab as part of a post-baccalaureate program to prepare for graduate school. At the time, the world, including our government, was concerned about potential biological warfare using smallpox virus. Therefore, there was a lot of government funding to study and develop vaccines for smallpox and I was part of the team who studied and developed the smallpox microarrays for identification of vaccine targets. I made a full circle and came back to this lab where I started my research. I find infectious disease a more relevant and interesting field. Our lab currently has produced a coronavirus array which is being tested with “serum” from infected patients to see if it can be used as a diagnostic tool to find out whether individuals are infected.
Hazel: How interesting! What did you study in graduate school?
Jenny: I got into UCLA and completed a PhD in Cellular and Molecular Pathology. I was interested in cancer research at the time, thus my project involved studying small molecule therapeutics used as treatments against cancer, in particular leukemia. I worked at City of Hope subsequently and did research looking for therapeutic targets for drug resistant melanoma research. I did this for 2 years. Then, I accepted a full-time college teaching job at Whittier College.
Hazel: Did you like teaching at the college? Did having a research background come in handy?
Jenny: I loved teaching so much! Having a research background certainly helped. I think teaching science in a way that is relevant is what keeps students interested and motivated. Guiding them to gain experience in the lab and advising them on their career prospects is very rewarding. At Whittier, I had the opportunity to mentor students in my own independent research project. I firmly believe, to teach science properly, you have to provide hands-on experience for students. There is nothing better than getting them in the lab and excited about science and also to teach them relevant experimental methods. This experience is something they can use post-graduation.
Hazel: What courses did you teach in college?
Jenny: I taught molecular biology, anatomy and physiology, general biology, cancer biology and liberal arts courses connecting cancer to our society. Whittier College had been identified as a Hispanic serving institution (HSI) and received several million dollars of grant money from Department of Education to create curriculum that would enable under-represented students to obtain a science degree in college. I was so honored to have had the opportunity to be part of this effort. I mainly designed courses to help first-generation college students to succeed in their science classes and ultimately graduate with a science degree.
Hazel: That is incredible! Were you not a first-generation college student yourself?
Jenny: Yes. I was the first person in my family to be going to college. My parents came from El Salvador in the 70s and had my sister and me in America. My mother’s education ended at third grade and my dad received some high school education, but they were always adamant that I obtained higher education.
Hazel: What an achievement, Jenny! Your family must be so proud of you! It must have been such a difficult journey though to go all the way to receive your PhD.
Jenny: At the beginning when taking undergraduate biology courses at University of Southern California, I struggled a lot. Everyone seemed to know how to study and what to do while I had no clue. Luckily, there were a lot of resources and people out there to help me. I had encountered some incredible people such as Mrs. Marroquin, our AP Biology teacher, and Raul Vargas of the USC Mexican Alumni Association who walked me through the financial aid process even before I even applied to college. Having these mentors guide me was what got me into college. When creating science curriculum for Whittier College, I drew from my own experiences and challenges. I felt that it was my turn to help others as much as others helped guide me.
Hazel: Oh yes. I remember Mrs. Marroquin. She was an inspiration to us all! Tell me in more detail what you emphasized when designing the courses.
Jenny: Giving the students confidence was the first thing. I often felt I did not belong in college or that I was not smart enough. I wanted them to believe in themselves and realize that if they put in hard work and reached out for help, they would be successful in their classes. I tried to expose them a balanced curriculum in science, including biology, chemistry, physics, math, and writing. I also made myself available for students to reach out to directly, which often times they did. I also tried to make science fun, because ultimately that is what keeps students interested.
I have always tried to stay involved in community outreach programs throughout my career that would get all students of all backgrounds and genders interested in science. When I was working at City of Hope, I volunteered with a colleague to teach science to 2nd graders at schools in Duarte School District through a program called the science education partnership award (SEPA) to promote science among diverse student populations. I have also volunteered to give talks through the Adelante Mujer Latina conference hosted by Pasadena city college to encourage junior high and high school girls to pursue careers in science.
It was so lovely to see my high school lab partner again. It’s funny how people are the same at the core even after so many years and life experiences. Jenny was still the same genuine, kind and warm person I remembered her to be when I first met her at my tender age of 15. I was also so glad to be educated more on vaccine biology and am thankful for scientists like Jenny who works hard daily to keep us all healthy. At a time like this where the whole world is engulfed by fear for Coronavirus, her heartfelt dedication to her research is even more greatly appreciated. Thank you, Dr. Jenny Hernandez-Davies for making time during your busy schedule. I wish you the very best in your career and life in general.