What it takes to make a winning vaccine & Why clout matters

In the early 2000s, the world experienced its first major outbreak from a coronavirus, SARS-CoV-1, when SARS afflicted Asia. [1] Roughly a decade later, a new strain of coronavirus emerged in the Middle East, now known as MERS-Cov. [2] And now here we are, another decade later, with yet another coronavirus outbreak with symptomatology reminiscent of the past two outbreaks.

The last two coronavirus outbreaks in Asia and in the Middle East inspired impressive measures to curb the spread of disease and to develop a safe and effective vaccine. So, why is it that we don’t actually have a vaccine for either of these diseases, and how does that impact our current response? The universal law of cause and effect stipulates that any action becomes a cause of the events that will follow… or, as JT put it, what goes around comes around. So, we did some digging on the protocol required to develop a vaccine, the events that transpired during the previous two outbreaks, and how this impacts the potential to bring a COVID-19 vaccine to market.

According to the CDC, there are 6 stages of vaccine development that are illustrated below:

Vaccine trials could take anywhere between months or years to complete since study subjects need to be evaluated for a sufficient time period to assess the development of required antibodies. [3,4]

Throughout this process, health professionals, academia, manufacturers, nongovernmental organizations, government agencies, media, and individuals and communities are all major stakeholders who directly impact the production of a potential vaccine. [5] “From the creation of the idea to having a marketable vaccine is usually 7 to 10 years or more, and about 1 billion U.S. dollars,” says Gregory A. Poland, MD, director of the Mayo Vaccine Research Group. [6]

Yet, advancements in technology coupled with an extensive response from galvanized stakeholders has allowed researchers to accelerate the timeline to begin vaccine trials. It took 20 months for researchers to begin a phase 1 clinical trial of a DNA vaccine candidate during the SARS outbreak. Researchers compressed this timeline to just 3 months since they first obtained the genomic sequence for SARS-CoV-2. [7] Impressive right?

The National Institutes of Health (NIH) launched a Phase I clinical trial at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle with 45 adult volunteers on March 16th. [8,9] The mRNA-1723 vaccine was fast-tracked because the National Institute of Allergy and Infectious Disease (NIAID) Vaccine Research Center (VRC) and Moderna were already working on an investigational MERS vaccine. [8] Once the genetic information of the SARS-CoV-2 strain was available, the spike protein that represents this strain was selected to be expressed in the existing mRNA platform. [10]

So, why didn’t all of this foundational research lead to the development of a SARS/MERS vaccine earlier?

Researchers in infectious disease posit that responses to infectious diseases tend to be cyclical—“…outbreaks lead to a surge in research investment, and if and when those outbreaks wane, as they invariably do, other priorities take their place,” said Jason Schwartz, a professor at the Yale School of Public Health. [11] Dr. Peter Hotez, co-director of the Center for Vaccine Development at Texas Children’s Hospital and Dean of the National School of Tropical Medicine at the Baylor College of Medicine mirrored this sentiment when he testified before the House Committee on Science, Space and Technology. [12]

In 2016, Dr. Hotez pushed for funding to further the development of the SARS vaccine that his team had created in collaboration with scientists at the University of Texas Medical Branch at Galveston. Yet, Dr. Hotez notes that with 10 years having passed since the SARS outbreak, they just couldn’t generate interest to source funding. [11] Vaccine development is time-consuming and profit margins are murky. Compared to drugs that require periodic administration, vaccines are administered just once a year or once in a lifetime. [13]

The Coalition for Epidemic Preparedness Innovations (CEPI) estimates that $2 billion is necessary to support the development of a vaccine for COVID-19. Thus far, several drug manufacturers including Moderna Inc, Inovio Pharmaceuticals Inc, Novavax Inc. and Johnson & Johnson have already begun efforts to develop experimental vaccines. And for the first time two major pharmaceutical giants, Sanofi SA and GlaxoSmithKline PLC, have partnered to collaborate on an experimental vaccine and to provide the manufacturing capacity necessary to bring a vaccine to market. [14] So, it seems like the appropriate stakeholders are rising to the occasion.

But ultimately, vaccine development seems to be reactive and market driven, and while COVID-19 has become the focal point of research now, sustained investments are likely necessary to carry this research to the finish line. Is the influence of COVID-19 enough to generate the funding necessary to advance research further than the previous two outbreaks? Now the question really remains: in terms of coronaviruses, will the third time be the charm?

Follow us @thepineperspective for more, and stay tuned for our next post where we’ll be zoning in on vaccine efforts for COVID-19 to date!

Primary Author:

Shruthi Patchava

B.A. Neurobiology & French | UC Berkeley

MPH Candidate | Dartmouth College

Contributors:

Monica Ngyuen, Minda Liu, Arushi Krishnan, Divya Chawla

MPH Candidates | Dartmouth College

References:

1. SARS Basic Fact Sheet. Severe Acute Respiratory Syndrome (SARS). https://www.cdc.gov/sars/about/fs-sars.html. Updated December 6, 2017. Accessed April 17 2020.

2. About MERS. Middle East Respiratory Syndrome (MERS). https://www.cdc.gov/coronavirus/mers/about/index.html. Updated August 2, 2019. Accessed April 17, 2020.

3. Vaccine Testing and the Approval Process. Vaccines & Immunizations. https://www.cdc.gov/vaccines/basics/test-approve.html. Updated May 1, 2014. Accessed April 17, 2020.

4. Vaccine Development, Testing, and Regulation. The History of Vaccines. https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation. Updated January 17, 2018. Accessed April 17, 2020.

5. Producing Prevention: The Complex Development of Vaccines. Milken Institute School of Public Health | The George Washington University. https://publichealthonline.gwu.edu/blog/producing-prevention-the-complex-development-of-vaccines/. Published March 6, 2019. Accessed April 18, 2020.

6. Boyle P. Here’s why we can’t rush a COVID-19 vaccine. AAMC. https://www.aamc.org/news-insights/here-s-why-we-can-t-rush-covid-19-vaccine. Published March 31, 2020. Accessed April 18, 2020.

7. Paules CI, Marston HD, Fauci AS. Coronavirus Infections—More Than Just the Common Cold. JAMA. 2020;323(8):707–708. doi:10.1001/jama.2020.0757

8. NIH clinical trial of investigational vaccine for COVID-19 begins. NIH National Institutes of Health. https://www.nih.gov/news-events/news-releases/nih-clinical-trial-investigational-vaccine-covid-19-begins. Published March 16, 2020. Accessed April 17, 2020.

9. Kaiser Permanente launches first coronavirus trial. Kaiser Permanente Washington Health Research Institute. https://www.kpwashingtonresearch.org/news-and-events/recent-news/news-2020/kaiser-permanente-launches-coronavirus-vaccine-study-seattle. Updated April 3, 2020. Accessed April 17, 2020.

10. NIH Scientists Identify Atomic Structure of Novel Coronavirus Protein. NIH National Institute of Allergy and Infectious Disease. https://www.niaid.nih.gov/news-events/atomic-structure-novel-coronavirus-protein. Published February 19, 2020. Accessed April 17, 2020.

11. Hixenbaugh M. Scientists were close to a coronavirus vaccine years ago, Then the money dried up. NBC News. https://www.nbcnews.com/health/health-care/scientists-were-close-coronavirus-vaccine-years-ago-then-money-dried-n1150091. Published March 5, 2020. Updated March 8, 2020. Accessed April 18, 2020.

12. Coronaviruses: Understanding the spread of infectious diseases and mobilizing innovative solutions. https://science.house.gov/hearings/beyond-coronaviruses-understanding-the-spread-of-infectious-diseases-and-mobilizing-innovative-solutions. Published March 5, 2020. Accessed April 17, 2020.

13. Lam B. Vaccines are profitable, so what? The Atlantic. https://www.theatlantic.com/business/archive/2015/02/vaccines-are-profitable-so-what/385214/. Published February 10, 2015. Accessed April 17, 2020.

14. Roland D. GlaxoSmithKline, Sanofi Team Up for Coronavirus Vaccine. The Wall Street Journal. https://www.wsj.com/articles/glaxosmithkline-sanofi-team-up-for-coronavirus-vaccine-11586875480?cx_testId=3&cx_testVariant=cx_2&cx_artPos=1#cxrecs_s. Published April 14, 2020. Accessed April 18, 2020.