In the midst of a pandemic where families sheltered in place and socially distanced, there was a long period of waiting for what would grant us all a sense of normalcy again– a vaccine.
Vaccines play an integral role in protecting individuals from infectious diseases, and at a time when knowledge about COVID-19 was only just developing, many scientists dropped everything to pivot their research towards vaccine development. While therapeutics can target severe symptoms, effective vaccines are also necessary to protect high risk populations, prevent transmission, and ultimately save lives.
An interdisciplinary approach to COVID-19 vaccine development
Dr. Young Kwon, a professor at UCI’s School of Pharmacy and Pharmaceutical Sciences, began working on the development of a novel, cell-free, cellular COVID-19 vaccine, “we developed immune cell-derived vesicles that closely mimic the parent cell’s T cell simulation capability, but without safety, storage, and distribution concerns like live cells, and we call them cell-free, cellular vaccines,” says Kwon.
Kwon’s interdisciplinary expertise in gene therapy, nanomedicine, and cellular vesicles places him in a unique position for the development of an innovative COVID-19 vaccine that requires genetic engineering of immune cells, novel nanoscale formulation, and preparation of immune cell-derived vesicles.
Also contributing to the project was co-investigator, Donald N. Forthal, M.D., Chief at the Division of Infectious Diseases and Professor at UCI’s School of Medicine. This interdisciplinary collaboration at UCI creates a perfect blend of expertise in pharmaceuticals, infectious disease, and medicine, that is necessary for combatting the COVID-19 pandemic.
According to Kwon, “this strong interdisciplinary collaboration will rapidly develop a transformative vaccine platform for COVID-19 with the potential for healthcare applications in a broader context.”
Non-traditional v. traditional methods of vaccine development
Throughout the pandemic, scientists have chosen both traditional and non-traditional methods to develop COVID-19 vaccines. Some of the traditional methods include: nucleic acids that encode coronaviral proteins, purified coronaviral proteins, and harmless coronaviruses.
In contrast, Dr. Kwon is utilizing a non-traditional method which aims to employ novel vesicles obtained from optimally activated immune cells and develop a highly potent and safe COVID-19 vaccine that ensures not only boosted but also prolonged protection.
“The innovative nature of this research involves developing a novel, immune cell-derived vaccine platform to stimulate the immune system to generate a highly orchestrated and comprehensive response, including generation of neutralizing antibodies and eradication of virus-infected cells, mimicking the most potent process that our body would mediate but in the most efficiently deliverable manners,” says Kwon.
How does this vaccine differ from other vaccines?
Kwon describes how other vaccines, such as mRNA, protein, and viral vaccines, must be efficiently delivered and appropriately processed by specialized immune cells, requiring a relatively large quantity to be given. In addition, adjuvants (immune-activating excipients) are indispensably needed to ensure an elevated immune response, which unavoidably generates adverse effects.
The immune cell-derived vesicle vaccines are made ready to stimulate the immune system with optimized machineries. For mRNA vaccines, this can only be achieved after multiple steps including successful antigen expression, avoided non-specific response, uptake and processing by specialized immune cells, and provision of additional immune stimulation. These processes are not efficient nor warranted, limiting the mRNA vaccine efficacy overall.
Furthermore, Kwon explains how the cell free, cellular vaccine, “bypasses the steps that potentially generate toxicity and lower efficacy, but directly engineers the central step in generating immune responses.” He added, “Conventional vaccine strategy is like dropping armors to the battle field with a hope that they survive the landing and are eventually picked up and used by the soldiers who know how to use them, while our approach is to create and deploy robots that are designed to most effectively fight against the enemy.”
Other major benefits of this cell-free, cellular vaccine include its potential for rapid large scale production and storage capacity in an off-the-shelf drug form.
What is the current status of the project?
Currently, the team has succeeded in preparing immune cell-derived vesicles that are optimally engineered for the desired immune response against SARS-CoV-2. Groups of mice have received prime and booster vaccines made of the immune cell-derived vesicles, and serological confirmation of SARS-CoV-2-neutralizing antibodies will be carried out soon.
The current climate has created an added layer of complexity for lab work: “We are challenged by various limitations: time allowed for researchers in the lab, availability of shared facilities, difficulties in timely purchasing reagents and services, and challenges of remote communication.” Despite the challenges, Kwon and his lab continue to persevere, while staying focused on the ultimate goal of mitigating the effects of the pandemic and saving lives.
In addition to Kwon, several other faculty at UCI’s School of Pharmacy and Pharmaceutical Sciences are contributing to fight against COVID-19:
Learn more about Dr. Chaput’s efforts to create COVID-19 therapeutics.
Read about UCI’s Innovator of the Year, Dr. Zhao’s development of a highly accurate serology test COVID-19 test.
By: Nedda Bozorgmehri / UCI