The Promise of a COVID19 Vaccine

Rapid progress is being made toward delivering a viable vaccine for the coronavirus responsible for COVID19.  For example, researchers at Inovio Pharmaceuticals were able to design a vaccine in just three hours once they received a sequence for the virus.  Along with a team of scientists from the University of Pennsylvania and the Wistar Institute, Inovio has been working on that vaccine since this past January.  And after just 83 days, they began the first human trial, which represents an absolutely unprecedented level of speed.

The research already completed proves that the vaccine works “in a test tube.” The new phase of the study involves testing the vaccine in low-risk people just to make sure the vaccine is well-tolerated by humans. Approximately 40 people are being tested during the so-called Phase-One Clinical Trial at locations in Kansas City and at the University of Pennsylvania. The final results from this test are expected this summer.

If no problems with patient tolerance emerge, Inovio will proceed with a Phase-Two Clinical Trial, in which the “at-risk population” will be tested. Phase-two is where they test it on larger numbers of patients and confirm the vaccine’s efficacy in humans. In preparation for Phase-Two, Inovio has already produced enough dosing for several thousand test subjects.

This is not the first time the firm has been asked to move at lightning speed. Using proprietary digital mapping of DNA sequences, Inovio was able to get a Zika virus vaccine to market in just seven months. However, getting a corona vaccine to market may take longer. Inovio recently received a $9 million grant from the Coalition for Epidemic Preparedness Innovations for the express purpose of speeding up the process of getting its vaccine to market.

Why the delay? “Expanded efficacy studies,” which are called Phase-three Clinical Trials, normally take a very, very long time. Thats why vaccine development, typically takes years or even decades.  At best, to commercialize a licensed vaccine taking the normal path, were usually talking about a year-and-a-half to two years. That’s the figure that’s been quoted by the CDC and others.

But as Wistar’s Dr. David Wiener points out, that doesnt necessarily mean that we wont see a coronavirus vaccine being used much sooner, as we did in the case of Ebola. According to Wiener, once the Ebola vaccine in West Africa was tested through phase one, the researchers “did an exceptionally clever trial design,” which enabled them to use a relatively small number of people in a very quick phase two trial.  Similarly, Weiner believes that high-risk populations could such as the elderly receive the vaccine much sooner and if needed, an “emergency use authorization” could be issued.

An emergency use authorization is where researchers get through early studies and show that a treatment is safe; then, they are given permission to start distributing it more widely. This approach is not usually used, but there has been a lot of discussion of emergency use of the COVID19 vaccine triggered by a group at Oxford University, which is going to start their vaccine trial sometime in the summer.

Importantly, even if Inovio’s vaccine candidate fails to reach commercialization, one or more of the several dozen other candidates now in the pipeline, are likely to do so. The Coalition for Epidemic Preparedness Innovations (or CEPI) mentioned earlier, is working with global health authorities and vaccine developers to support the development of a vaccine against COVID-19. To facilitate this effort, they are continuously maintaining their so-called “landscape database” of vaccine development programs identified from publicly available and proprietary sources.

As of April 8, 2020, the global COVID-19 vaccine R&D landscape database included 115 vaccine candidates, of which 78 were confirmed as active projects and 37 were still unconfirmed by CEPI.  Of the 78 confirmed active projects, 73 were still at exploratory or preclinical stages, while the most advanced candidates had recently moved into clinical development. These clinical candidates include mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio, and LV-SMENP-DC as well as pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute.  Numerous other vaccine developers had already indicated plans to initiate human testing in 2020.

In terms of resources, the U.S. government is stepping in to help. In early April, it announced collaborations with Johnson & Johnson and Moderna to simultaneously support clinical testing and the development of production infrastructure for COVID-19 vaccines. On March 30, Johnson & Johnson announced a joint investment with the U.S. government of $1 billion intended to create the capacity to manufacture more than 1 billion doses of a vaccine; the efforts will be funded in part by roughly $420 million from the U.S. Government. The funding will support non-clinical studies, according to the statement, as well as a Phase 1 clinical trial of Ad26 SARS-CoV-2, an investigational vaccine for COVID-19 developed by Janssen, a pharmaceutical subsidiary of Johnson & Johnson. According to the journal Science, this vaccine uses the same technology as Janssen’s investigational Ebola vaccine, which became available in the Democratic Republic of Congo in November 2019. The phase one clinical trial for this vaccine is set to begin no later than this coming fall and it could produce a vaccine available for emergency use in the U.S. in early 2021.

The agency has also committed to supporting Moderna in Phase 2 and 3 clinical trials of its COVID-19 vaccine, called SARS-CoV-2 mRNA-1273. The Phase 1 study for the vaccine, developed in partnership with the National Institute of Allergy and Infectious Diseases, got underway in early April.

On April 28, Pfizer Inc. said it could have a vaccine ready for emergency use by the fall.  Pfizer CEO Albert Bourla told The Wall Street Journal that the company could be ready for a broader rollout involving millions of doses by the end of the year.

A U.S. government agency called BARDA intends to support five or six vaccine candidates, out of which two or three may ultimately be successful. Its goal is to work as quickly as possible to manufacture enough vaccine for the United States, as well as the rest of the world.

Given this trend, we offer the following forecasts for your consideration.

First, the United States and the UK will use “emergency use authorization” to get a viable vaccine to the public later this year.

This is consistent with the “right to try legislation” President Trump championed in his first year in office. And since both Trump and Boris Johnson recognize the importance of managing expectations, expect them to under-promise and over-deliver. Once Phase 1 trials establish an absence of toxicity or serious side-effects, barriers to deploying a vaccine that seems to be efficacious to all high-risk populations will be minimal. This will have an enormously powerful impact on economic activity and public opinion.

Second, rolling out billions of doses of the vaccine worldwide in 2021 will bolster America’s image and further undermine Chinese credibility.

In the coming era of Sino-American conflict, international perceptions will mean more than military might. By providing a solution to a global crisis created by China, the United States will regain any credibility with allies lost due to “America First” policies. Expect China to follow a similar course if they can develop and produce an effective vaccine on such a timetable. China will almost certainly employ industrial espionage in their attempt to beat the U. S. to a solution.

Third, what we’ve learned from the extraordinarily accelerated timeframe for a COVID19 vaccine will make future pandemics less disruptive.

The global vaccine R&D effort in response to the COVID-19 pandemic is unprecedented in terms of scale and speed. Given the imperative for speed, vaccines could be available to the general public under “emergency use protocols” by early 2021 and to high-risk populations much sooner. This represents a quantum leap from the traditional vaccine development pathway, which takes on average over 10 years; and it’s much faster than the accelerated 5-year timescale for the development of the first Ebola vaccine.  Delivering on this forecast will necessitate the use of novel vaccine development paradigms involving parallel and adaptive development phases, innovative regulatory processes, and scalable manufacturing capacity. In order to assess vaccine efficacy, COVID19-specific animal models are being developed, including ACE2-transgenic mice, hamsters, ferrets, and non-human primates. And,

Fourth, like the flu vaccines, the COVID19 vaccine will be indispensable even if it’s not 100% effective against every new strain that mutates.

When all is said and done, emerging evidence will show that COVID19 is no more lethal than a normal influenza virus. However, it is much more contagious, meaning that without a vaccine more people will get it and so more people could die.  Consequently, much of the panic will turn out to have been fueled by misinformation coupled with a lack of identified treatments or vaccines. We’ll see that outside of the New York area, the response was worse than the disease.  Fortunately, the combination of viable treatments, isolation of high-risk populations, and the widespread availability of a relatively effective vaccine will enable us to put the panic behind us in 2020 and approach COVID19 like any other influenza virus of the past 50 years.

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References
1. The Scientist. April 1, 2020. Amy Schleunes.  US Selects Two COVID-19 Vaccine Candidates for Huge Investments.  

https://www.the-scientist.com/news-opinion/us-selects-two-covid-19-vaccine-candidates-for-huge-investments-67367

2. The Scientist. April 1, 2020. Jef Akst. COVID-19 Vaccine Frontrunners. 

https://www.the-scientist.com/news-opinion/covid-19-vaccine-frontrunners-67382

3. com. April 16, 2020.  Nicolletta Lanese.  When will a COVID-19 vaccine be ready? 

https://www.livescience.com/coronavirus-covid-19-vaccine-timeline.html

4. Medical News Today. April 17, 2020.  Ana Sandoiu.  COVID-19: Vaccine may be ready by fall and other reasons for hope. 

https://www.medicalnewstoday.com/articles/covid-19-vaccine-may-be-ready-by-fall-and-other-reasons-for-hope

5. April 9, 2020.  Tung Thanh Le, Zacharias Andreadakis, Arun Kumar, Raul Gomez Roman, Stig Tollefsen, Melanie Saville & Stephen Mayhew.  The COVID-19 vaccine development landscape. 

https://www.nature.com/articles/d41573-020-00073-5

 
6. com. April 22, 2020.  Perry Chiaramonte & Angela Bertorelli.  Possible coronavirus vaccine enters human testing trial. 

https://www.foxnews.com/health/possible-coronavirus-vaccine-human-testing-trial