The Application of Microphysiological Systems for Vaccine Development

By Elyse Harris

Microphysiological Systems (MPS) Compared to 2D Models

Many limitations of the vaccine development process can be overcome by using microphysiological systems (MPS). MPS can include in vitro organ-like structures or organoids derived from human cells, which can be used to study drug safety and efficacy 1. The use of human organoids contrasts the use of more traditional methods; cell monocultures, immortalized cell lines, or animal models1. Animal or 2D in vitro models do not fully represent the three dimensional (3D) dynamic features of human tissues, and thus, do not produce clinically translatable results. Additionally, species differences hinder translating drug screening results into human clinical trials. On the other hand, 3D cell culture techniques can be used to create highly predictive in vitro models for drug discovery, cancer research, and toxicity screening because of their ability to mimic the tissue characteristics1. Organoids that resemble lungs, as well as the brain, kidney, stomach, and liver have already been produced2. Microfluidic and organ-on-chip devices are becoming popular for culturing organoids. The fluidic channels resemble blood, carrying the drug candidate and allow oxygen delivery3. Additionally, some microfluidics are transparent, allowing live imaging to record the organ’s response to drug candidates3.

Microfluidic Devices Recapitulate Human Organs

Due to their flexibility, microfluidic devices can mimic breathing motion, which is critical to recapitulating lung organoids. Thus, organoids can be used in evaluating toxicity and efficacy of drug candidates and generate results translatable to clinical trials, increasing the likelihood of in vivo success 2. Moreover, using 3D organoids contributes to reducing or replacing animal models and study of diseases that lack animal models. The use of MPS would be particularly beneficial for accelerating the vaccine development and treatment of less well understood pandemic diseases such as COVID-19 because of their ability to better recapitulate human physiological processes.

MPS Devices for COVID-19 Vaccine Development

For COVID-19, the need for technologies that can make vaccine development more efficient, such as MPS, is rising. COVID-19 presents respiratory issues ranging from shortness of breath and cough to pneumonia and different forms of lung failure. Evaluating the efficacy of treatments and vaccines for respiratory diseases is difficult in animal models because their physiology and pathology differs from humans4. For example, biomarkers of respiratory infection may appear later in the disease’s progression in animal models than in humans4. Furthermore, using antibodies from recovered humans in organoids has the potential to test their efficacy better than in animal models because they can mimic innate and adaptive immune responses in vitro5. This can be a method for COVID vaccine development, as similar models have been successfully used to evaluate immunogenicity of influenza vaccines5.  Fortunately, models that use airway organoids (Figure 1) can be cultured with different immune cells and have proven suitable for studying SARS-CoV-2 infectivity6. Lung organoid models present the potential to study immunological responses to COVID-19 and include the ability to recapitulate the cytokine storm6 for better understanding severe COVID-19 symptoms and identifying potential treatments.

Figure 1: Airway organoids, representing airway and alveolar epithelium, are successfully used to study infectivity and cytopathy of SARS-CoV-2. Modified from Elbadawi et al.6


MPS: Limitations and Future Applications

However, there are some limitations of MPS. For example, full maturational of organoids to adult organs or tissues is a challenge, organoids are more expensive than traditional 2D cultures, and size variation of spheroids results in high experimental variability1. Despite these limitations, 3D cell culture techniques can overcome the limitations of 2D techniques and in vivo animal models to accurately evaluate drug screening and capture side effects to increase the success rate of therapy and vaccine development. Given the medical and economic urgency for a COVID-19 therapies and improved vaccines, the application of MPS in this area is a valuable resource.



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  2. Watson DE, Hunziker R, Wikswo JP. Fitting tissue chips and microphysiological systems into the grand scheme of medicine, biology, pharmacology, and toxicology. Experimental Biology and Medicine. 2017;242(16):1559-1572. doi:10.1177/1535370217732765
  3. Wu Q, et al. Organ-on-a-chip: recent breakthroughs and future prospects. Biomedical engineering online. 2020;19. doi:10.1186/s12938-020-0752-0
  4. Williams K, Roman J. Studying human respiratory disease in animals – role of induced and naturally occurring models. The Journal of Pathology. 2015. doi: 10.1002/path.4658
  5. Busquet F, Hartung T, Pallocca G, et al. Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines. Arch Toxicol. 2020; 94:2263–2272.
  6. Elbadawi M, Efferth T. Organoids of human airways to study infectivity and cytopathy of SARS-CoV-2. The Lancet Respiratory Medicine. 2020; 8(7): e55-e56. doi: 10.1016/S2213-2600(20)30238-1.