ImmunoVida: A Recombinant Quadrivalent Influenza Vaccine for Latin America; Sex as a Biological Variable: Eliminating Gender Bias in Research Design

Author:
Holbrook, Mia, School of Engineering and Applied Science, University of Virginia
Advisors:
Wayland, Kent, EN-Engineering and Society, University of Virginia
Anderson, Eric, EN-Chem Engr Dept, University of Virginia
Abstract:

Vaccines have been providing immunity against specific infectious diseases to people for years by stimulating the immune system to recognize and fight pathogens. One of the many vaccines that are used annually is the influenza, or flu, vaccine. The influenza virus has been a significant global health challenge with 3-5 million severe cases and up to 650,000 deaths annually. Seasonal influenza epidemics disrupt productivity and overwhelm healthcare systems, particularly in developing regions like Latin America where healthcare infrastructure is more limited. The most effective strategy to reduce the spread of these infectious diseases and reduce hospitalizations remains to be the widespread distribution of vaccines. During the development of vaccines and other similar biomedical technologies, gender bias in research has been another ongoing problem that has only recently begun improving. One of the major problems has been the lack of representation of the female sex, as well as other minority populations, in preclinical and clinical trials because it has led to unprecedented side effects and even deaths. Over the past few decades, the US government has started to address this discrepancy.
The proposed solution to the high number of flu cases in Latin America is ImmunoVida, a recombinant quadrivalent influenza vaccine designed to provide broad protection against influenza A and B subtypes in individuals aged 18 and older. This facility will be located in São Paulo, Brazil and aims to produce 90 million doses per year. The upstream process includes an Sf9 insect cell seed train infected with purchased baculovirus across eight 10,000 L bioreactors, yielding 1.56 kg of HA antigen per run. These harvested cells proceed to a downstream purification train that begins with two centrifugation steps, followed by anion exchange chromatography, cation exchange chromatography, ultrafiltration, diafiltration, hydrophobic interaction chromatography, viral filtration, and a final diafiltration step. The final drug product is filled into single-dose glass vials. The proposed plant will produce nine batches per year, yielding 18.08 kg of HA (4.52 kg of each strain) annually. It will operate for 18 weeks of the year, with the remainder of the year dedicated to research and development activities, seed train expansion, and rented to outside companies for other applications. Economic analysis confirms strong financial viability of the facility. The total capital investment is estimated at $100.9 million, with annual operating costs of $134.7 million per year. Depending on market conditions, yearly revenue is projected between $315 million to $705 million. A 10-year financial production across best, mid, and worst-case scenarios shows return of investment ranging from 978% to 3773%, confirming the profitability of the project and viability to investors.
The prevalent gender bias issue in biomedical research started to be addressed by the US government in 1990. The US National Institute of Health (NIH) began to require the inclusion of women in NIH funded clinical trials and while this had positive results, women continued to be severely affected in comparison to men. Starting in 2016, the NIH required all applicants that intended to work with vertebrate animals or humans to factor sex as a biological variable (SABV) into their research and analysis or to provide strong justification for single-sex investigations. To see how this policy has affected science culture on smaller scales, the top ten high impact health science research journals were investigated. During this investigation, the expectations for reporting sex and gender were observed and the frequency of the terms ‘sex’ and ‘sex as a biological variable’ per year were analyzed. It was found that the journals updated their reporting policies following the pandemic by creating their own policy or strongly recommending their author to follow the Sex and Gender Equity in Research guidelines. Additionally, the phrases have fluctuated in frequency since 2015 most likely due to the pandemic and journal policies not being adjusted until recently. There was seen to be an overall increase from 2023 to 2024, showing that this policy has started to influence how medical research is designed on smaller scales. This will ideally lead to a change in scientific culture, making female representation an expectation rather than a suggestion.
Overall, I thought the research I have conducted this semester has been extremely valuable. My technical capstone group was able utilize the knowledge we’ve gained from our chemical engineering courses to accomplish all of our intended goals. For any groups that may choose to continue our work in the future, we recommend incorporating a baculovirus expression train rather than outsourcing it and to do a sensitivity study on the economic and environmental impact of CIP/SIP procedures vs single-use equipment. During my STS research, the policy I was studying unfortunately was reversed by the government. Additionally, the NIH froze their funding which caused me to have to adjust my method of research. If future researchers were to continue my work, I would encourage them to interview researchers at UVA to analyze how the policy affected research design on a smaller, more local scale.

Degree:
BS (Bachelor of Science)
Keywords:
Vaccine, Gender Bias, Chemical Engineering
Notes:

School of Engineering and Applied Science

Bachelor of Science in Chemical Engineering

Technical Advisor: Eric Anderson

STS Advisor: Kent Wayland

Technical Team Members: Michelle Harnisch, Diana Kirilov, Abby DeChurch

Language:
English
Rights:
All rights reserved (no additional license for public reuse)
Issued Date:
2025/05/12