When Will a COVID-19 Vaccine be Ready… and Why Then?

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Industry experts say a vaccine against the SARS-CoV-2 virus will either be ready this fall, at the end of the year or 18 months from now, depending on the vaccine and how they define “ready.”

Generally, those experts are talking about emergency use authorizations for targeted populations, such as healthcare workers, first responders and the elderly. Widespread, population-level vaccinations are unlikely to begin before sometime in 2021, Scott Gottlieb, former FDA commissioner, speculated in a CNBC interview.

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“Normal vaccine development takes 8 to 10 years,” Thomas Lingelbach, president and CEO of Valneva SE, said. “In principle, developing a new vaccine isn’t difficult. The human body creates antibodies to the virus, so drug developers are trying to build antigen that does the same.”

SARS-CoV-2 isn’t just another virus, though. It’s never been seen before and scientists are still learning its fundamentals. Given the potential of the threat, drug developers and regulators are doing everything in their power to expedite safe, efficacious vaccine development.

One of the challenges is how best to create an enduring immune response while minimizing ancillary immune responses. For example, researchers at Moderna working on its mRNA vaccine struggled to eliminate the double-stranded RNA (dsRNA) impurities produced during the synthesis process, which can cause an undesirable innate immune responses in vivo. It announced its solution June 2, an engineered Moderna T7 RNA polymerase (MT7) that does not produce presenting dsRNA impurities.

Of the dozens of COVID-19 vaccines in development, Moderna’s mRNA-1273 vaccine appears to be the furthest along. The company moved swiftly from day one, beginning to design a vaccine within days of learning of the coronavirus outbreak. On February 24 it announced it had shipped the vaccine to trial sites to begin Phase I clinical trials, and on May 29th announced it dosed the first patients in its Phase II trial. It expects to have a vaccine ready for emergency use this autumn.

Pfizer, with its mRNA vaccine BNT162, was a few weeks slower. It dosed its first cohort in Germany at the end of April and the first U.S. patients in Phase I/II trials in the U.S. in May. It predicts commercialization by the end of October and the manufacture of 10 to 20 million doses for emergency use by year’s end.

Part of the speed of development is because nucleic acid vaccines don’t require culturing or vat fermentation. Therefore, “Other approaches are unlikely to meet that timeline,” Lingelbach told BioSpace.

Speed may not confer success, of course.

“The mRNA technology was developed several years ago, but not a single mRNA vaccine has been approved,” Lingelbach said. “Everyone in this space now is working on the hypothesis that the SARX-CoV-2 vaccine will validate the technology.”

The advantage for mRNA vaccines is that they can be manufactured quickly.

Even if efficacious, they undoubtedly will compete with vaccines created through a variety of approaches, including recombinant proteins and replicating and non-replicating viral vectors created in cell cultures or possibly even traditionally.

“No single vaccine or vaccine platform alone is likely to meet the global need, and so a strategic approach to the multi-pronged endeavor is absolutely critical,” according to Anthony Fauci, M.D., Francis Collins, M.D., Ph.D., and co-authors, writing in Science.

AstraZeneca’s COVID-19 vaccine seems a likely challenger to the mRNA vaccines, based upon speed to market. It began Phase II/III trials in the U.K. in late May for its recombinant adenovirus vaccine, AZD1222. The company has contracts to supply 400 million doses equitably throughout the world, and plans to begin its first shipments in September for the UK.

Valneva’s cell culture-based production process, in contrast, may have a COVID-19 vaccine ready for clinical trials by the end of 2020. This cell-culture process was developed using the same manufacturing platform as IXIARO®, its already-commercialized Japanese encephalitis vaccine. VLA2001 is one of a few inactivated-virus vaccine strategy in development targeting COVID-19. Another is being developed by Sinovac Biotech Ltd. in Beijing.

“We can’t be as fast as the others because we deal with the (inactivated) whole virus,” Lingelbach explained. “We had to modify our facilities to Biological Safety Level 3 to allow this virus to be handled.”

The benefit that inactivated viral vaccines offer is their well-proven safety and efficacy record.

“This could be a complementary approach for the elderly or young children who may not want to use a vaccination approach that’s never been used before,” Lingelbach suggested.

Manufacturing scaleup is another hurdle. Some companies are investing in commercial-scale manufacturing facilities before safety and immunogenicity data are available, hoping their candidates will advance. For newer technologies, large scale manufacturing may never have occurred, leaving wide potential for failure. Traditional manufacturing methods, therefore, remain important.

Speed is only one aspect in the race to develop an effective COVID-19 vaccine, but it is an important one. Manufacturers in the U.S. are aided by Operation Warp Speed and, within it, the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) program sponsored by the National Institutes of Health. Comprised of U.S. and EU regulators, the Centers for Disease Control and more than a dozen biopharmaceutical companies, ACTIV is designing a framework to prioritize vaccine and drug candidates for regulatory review, streamline clinical trials, coordinate regulatory processes and perhaps leverage assets among all partners to rapidly respond to this and future pandemics.

Specifically for vaccines, ACTIV is:

  • mapping epitopes and developing assays
  • establishing protocols for sampling and for immunological analyses and reagents
  • collecting clinical data on immunological responses and endpoints
  • developing surrogate endpoints for clinical evaluation.

Before any vaccine can be administered, however, researchers still must determine what constitutes a protective immune response against the SARS-CoV-2 virus, level of immunity or the duration of protection, according to the Science article. That requires vaccinating a tens of thousands of people in controlled circumstances, Dr. Gottlieb pointed out on CNBC.

Given the magnitude of the unknowns, Dr. Fauci and colleagues wrote, “This constitutes another reason why a diversity of vaccine approaches must be pursued.”

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