The rapid pace of development for vaccines to protect against SAR-CoV-2 infection will highlight the strengths and weaknesses of various modalities- pitting the rapid development timelines for mRNA and DNA candidates against the pre-existing validation of 'slower' technologies.
While waiting on highly anticipated data from therapeutic candidates to fight COVID-19, the vaccine strategy has been crystallising this week after a series of optimistic timing updates from developers.
Pfizer announced that its partnership with BioNTech is progressing at pace, now with plans to follow Moderna Therapeutics into the clinic with a second mRNA vaccine candidate. The partners expect to start the first human trial this month, saying that BioNTech will contribute "multiple" mRNA candidates as part of its BNT162 programme. (See ViewPoints: Moderna, Gilead lead coronavirus charge)
Meanwhile, Inovio Pharmaceuticals said this week that it received FDA clearance for a Phase I trial of a DNA vaccine, INO-4800. It's conducting the study in healthy volunteers in two US cities.
Both candidates target the SARS-CoV-2 spike protein, and are joined by a variety of other companies using RNA or DNA approaches, including CureVac and Sanofi.
In the realm of more 'traditional' vaccines, Johnson & Johnson may be leading the way. The company recently disclosed that it expects to begin clinical studies in September- pushed up from an original estimate of November- of a candidate derived from its AdVac platform. The technology relies on the production of adenoviral vectors to deliver an immunogenic protein, and had been previously deployed against Ebola.
But a dark horse contender for an early approval comes out of China, where authorities acted nearly a month ago to permit human studies of an adenoviral vaccine candidate from CanSino Biologics. The company already has some solid antiviral experience behind it, having used the same platform to produce an Ebola candidate that was approved in China in 2017.
The bigger picture
COVID-19-directed vaccine partnerships have exploded over the last month, with both the public and private sector pitching in to bring down the longer clinical development timelines required for a vaccine versus a therapeutic. Because of their use in healthy patients, vaccine candidates will also have a much higher benchmark in terms of an acceptable risk/benefit profile.
The mRNA and DNA vaccines have been a low-hanging fruit of the effort, given their rapid design timelines and lower manufacturing burdens. However, few mRNA products have been validated in the clinic, with Moderna responsible for most of the recent clinical forays for the modality.
DNA vaccines are similar to the newly popular mRNA offerings in that they can be rapidly designed and manufactured, leaning on a patient's own cells to create the antigen protein encoded by the mRNA. While DNA vaccines are more stable and less immunogenic, they add an additional layer of complication by requiring that two separate steps successfully occur in the patient- transcription of the DNA into RNA in the nucleus, and translation into the immunogenic protein. Thus far the distinction is largely theoretical, with the COVID-19 pandemic perhaps serving as a pivotal test case of whether the modalities have legs, or which product profile fares better.
Purveyors of RNA and DNA vaccines have been quick to point to their manufacturing capacity, with Pfizer and BioNtech estimating that they could produce "millions" of vaccine doses by the end of 2020, and "hundreds of millions" in 2021. However, it's not as clear how quickly the non-mRNA/DNA version of COVID-19 vaccines might achieve the same scale-up. Johnson & Johnson said it is ramping up for a billion doses of its adenoviral-based candidate, but with no specific timeline disclosed. Hitting that benchmark will further involve the build-out of new US manufacturing sites, as well as "scaling up capacity in other countries."
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