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News Feature: Avoiding pitfalls in the pursuit of a COVID-19 vaccine

As they race to devise a vaccine, researchers are trying to ensure that their candidates don’t spur a counterproductive, even dangerous, immune system reaction known as immune enhancement. 

The teams of researchers scrambling to develop a coronavirus disease 2019 (COVID-19) vaccine clearly face some big challenges, both scientific and logistical. One of the most pressing: understanding how the immune system interacts not only with the pathogen but with the vaccine itself—crucial insights when attempting to develop a safe and effective vaccine.



Researchers are debating which, if any, of the phenomena related to immune enhancement could be at play in the case of the novel coronavirus—and just how these phenomena might affect the success of vaccine candidates. Image credit: Shutterstock/PhotobyTawat.



Researchers need to understand in particular whether the vaccine causes the same types of immune system malfunctions that have been observed in past vaccine development. Since the 1960s, tests of vaccine candidates for diseases such as dengue, respiratory syncytial virus (RSV), and severe acute respiratory syndrome (SARS) have shown a paradoxical phenomenon: Some animals or people who received the vaccine and were later exposed to the virus developed more severe disease than those who had not been vaccinated (1). The vaccine-primed immune system, in certain cases, seemed to launch a shoddy response to the natural infection. “That is something we want to avoid,” says Kanta Subbarao, director of the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne, Australia.

This immune backfiring, or so-called immune enhancement, may manifest in different ways such as antibody-dependent enhancement (ADE), a process in which a virus leverages antibodies to aid infection; or cell-based enhancement, a category that includes allergic inflammation caused by Th2 immunopathology. In some cases, the enhancement processes might overlap. Scientific debate is underway as to which, if any, …