06 May 2020
Human coronaviruses (HCoVs) in the past were considered to cause nothing more than the common cold in healthy people. That changed with the advent of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in the past decade. The latest coronavirus─2019-nCoV, since renamed by the World Health Organization as COVID-19─emerged in December 2019 in Wuhan, China. As of late February 2020, it had sickened tens of thousands and killed nearly 3000 people.
Four of these large, enveloped, positive-strand RNA viruses are endemic globally and thought to cause 10–30% of upper respiratory tract infections in adults (1). They possess a surface spike (S) glycoprotein that binds to host cell receptors, and the nature of this protein is believed to determine the main properties of each coronavirus. SARS-CoV was the first coronavirus to jump from animals to humans; MERS-CoV and COVID-19 have as well.
The genetic sequence for COVID-19 was released to public databases on Jan. 10, 2020 by the Shanghai Public Health Clinical Center & School of Public Health (1). The three-dimensional (3-D) structure of the spike protein suggests that it binds more tightly to human cell surface receptors than SARS-CoV, a possible reason that this coronavirus exhibits greater infectivity (2).
Platform diagnostic methods have been rapidly adapted to include COVID-19 for early identification of cases. Several academic and industrial researchers have also focused on applying novel vaccine development and manufacturing platforms to the accelerated development of a COVID-19 vaccine.
In terms of vaccine development and protection against dangerous viral pathogens, there is nothing particularly unique about coronaviruses, according to Eric von Hofe, chief scientific officer of NuGenerex Immuno-Oncology. “All of the recent potentially pandemic viruses, including SARS and MERS and two flu viruses (avian and swine flu), have the common feature that they simply had never been seen before by the human immune system. That said, we now know a lot about how the human immune system protects against viral infections and can rapidly identify the critical parts of a new virus to target for vaccine development,” he says.
Traditional vaccines, like the seasonal flu vaccine, are made by growing up large quantities of the virus and in some way killing or inactivating it so that it can be used safely as a vaccine. This approach is an old technology from the middle of the past century, according to von Hofe. “The main problem here is the time it takes to produce the vaccine, which is at least a year and can be several. Ideally, we’d have a platform technology that could be used to produce a vaccine in a few months,” he observes.
Such technology platforms should be flexible enough to respond to any new viral threat. “We would like to have a simple ‘plug-and-play’ setup where the critical components of a new virus required to make the vaccine can be determined by rapid computer analysis and plugged into the platform to generate a vaccine,” von Hofe notes. “Getting all of the critical components produced and structured in a way that perfectly models the vaccine is the big challenge,” he adds.
The best way, von Hofe says, is to follow a reductionist strategy to identify key viral components that alone produce complete protection in a safe vaccine that can be manufactured rapidly and in a cost-effective manner. “Clearly this is a tall order, but we’re making good progress in that direction,” he asserts.
As an example, he points to the development of subunit vaccines that rely on recombinant DNA to encode a critical subunit of the vaccine that generates a response. There are additional challenges to this approach, however. “While responses can be produced, the protection may be short-lived, as there is no guarantee that immunological memory will be generated as is possible with a whole virus vaccine,” von Hofe comments.
San Diego-based Inovio Pharmaceuticals is one company developing a DNA-based vaccine against COVID-19. The biotech was the first to advance a vaccine (INO-4700) against MERS-CoV into human testing and is currently preparing to initiate a Phase II trial for INO-4700 in the Middle East. This vaccine, however, cannot be used against COVID-19 because the two coronaviruses are too different.
To develop a new vaccine, Inovio first converts the virus’ RNA into DNA and identifies short sections that will, according to computer simulations, generate the greatest immune response. The plasmids are then produced in large quantities using bacteria. The overall development and approval timeline is thereby significantly reduced.
Inovio began animal testing of INO-4800, its COVID-19 vaccine candidate, in February 2020 and is aiming to begin human safety testing in early summer 2020. The company will conduct tests in both the United States and China, the latter in collaboration with Beijing Advaccine Biotechnology Co. (3). Work in the US is supported by a $9-million grant from the Coalition for Epidemic Preparedness Innovations (CEPI). The collaboration with Beijing Advaccine is anticipated to accelerate developed on INO-4800 in China by providing access to not only its vaccine expertise, but also its relationship and experience with Chinese regulatory authorities and clinical trial management in the country.Print
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