A spike in vaccine development

Te Herenga Waka—Victoria University of Wellington’s Dr Davide Comoletti is playing a pivotal role in New Zealand’s drive to develop a COVID-19 vaccine.

Dr Davide Comoletti
Dr Davide Comoletti

Dr Comoletti is working as part of Vaccine Alliance Aotearoa New Zealand—Ohu Kaupare Huaketo’s efforts to develop a COVID-19 vaccine in New Zealand. The team’s work has featured on TVNZ’s Sunday programme.

Primarily a neuroscientist, he has spent the past two decades studying the three-dimensional structure and function of a class of proteins called neuronal cell surface proteins—a skill that is now coming in handy in the New Zealand development of a COVID-19 vaccine.

“SARS-CoV-2 uses a spike protein on the outside of the viral cell to attach to the ACE2 receptor of the human cells in the lungs, before inserting the virus’ genetic material into human cells and infect them—this is the way for the virus to get inside human cells,” Dr Comoletti says. “If you look at any image of the virus, you can clearly see the spikes around the outside of the virus —it’s what gives the virus its distinctive ‘corona’ or crown-like appearance. Although this is a viral spike protein, it does have a few features in common with the cell surface proteins I have been working on.”

These spike proteins could be a key part of a COVID-19 vaccine, Dr Comoletti says. By using these proteins as an active ingredient in a vaccine, the human host could potentially develop an immunity to the spikes and prevent the virus from infecting human cells with its genetic material.

However, like neuronal cell surface proteins, these proteins can be difficult to recreate in a lab setting. Dr Comoletti is using his experience in studying neuronal proteins to help produce the SARS-CoV-2 spike protein in his lab.

“My role is to design and test production of the spike protein as a whole, as well as specific portions of the protein,” Dr Comoletti says. “Once we can produce high quality versions of the protein and protein fragments, they can be passed on to my immunology colleagues, who will investigate which of these stimulate best the immune system and should be used in a final vaccine.”

Once Dr Comoletti and his team have developed the most promising versions of the protein and fragments and tested them to make sure they assume the appropriate shape and stick to the ACE2 receptor, Vaccine Alliance Aotearoa New Zealand researchers will be able to move to the next stages of vaccine development, which is testing immune response.

“The optimal fragment will ideally stimulate a strong and long-lasting immune response against SARS-CoV-2 without harming the human recipient,” Dr Comoletti says.

Dr Comoletti and his team are continuously developing new spike fragments and he says the results have been promising so far.

“We’ve concluded the first round of fragment design and we have already been able to produce some of the proteins in large amounts, which is promising,” Dr Comoletti says. “Proteins need to be successfully produced in high amounts to ensure there is enough for testing, but also because in order to efficiently manufacture a vaccine it must be possible for the ingredients to be easily manufactured in high volumes.”

Dr Comoletti says the student and postdoctoral researcher who are working on this project expect to be able to create enough material over the next few weeks to allow in vitro testing to begin.

“This is an unprecedented situation, and because there is currently no proven treatment for COVID-19 immunisation of the New Zealand population is the safest strategy out of the current crisis,” Dr Comoletti says. “In this situation I am proud of being part of this project and to be working side by side with the most talented and smart people in this field in New Zealand.”