Platform Manufacturing May Speed Pandemic Vaccine Development

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Vaccines can be developed faster utilizing platform manufacturing technology.
Vaccines can be developed faster utilizing platform manufacturing technology.

Will the United States be ready for the next pandemic? With the advent of platform manufacturing technology, vaccines can be developed quickly to stop the spread of infectious disease outbreaks.1

The Need for Speed to Control Epidemics

While traditional vaccines for nonepidemic diseases can take up to 15 years to develop, platform vaccine manufacturing uses efficient processes established from previous similar vaccines that can permit the start of phase 1 testing just months after the viral sequence selection of the pathogen.1,2 As a result of this new platform paradigm, the time from viral sequencing of the pathogen to phase 1 trials of the vaccines has decreased from 20 months in 2003 during the SARS [serious acute respiratory syndrome] coronavirus outbreak to approximately 3 months during the 2016 Zika virus epidemic.1

“If you're testing vaccines in the middle of an outbreak, then you can clearly get what's called a ‘vaccine efficacy signal' pretty quickly,” explained Anthony S. Fauci, MD, director of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, in an interview with Infectious Disease Advisor. “If you're testing vaccines when there is a modest amount of cases, that's when it will take a few years before you get an efficacy signal.”

A familiar manufacturing process enables manufacturers to obtain faster approval from the US Food and Drug Administration (FDA) to combat epidemics because the agency knows the safety profile of similar previous vaccines.1,2 The 2 leading platform classes are nucleic acids and vectors.3 One example of the nucleic acid class is the DNA plasmid vaccine platform, which helped expedite vaccine manufacture for the Zika virus.1

“When you get used to working with a particular platform technology, it is interchangeable with whatever virus you're dealing with because you have a plasmid whose characteristics you know and you can insert an appropriate gene into the plasmid,” Dr Fauci indicated. “The FDA knows and understands the safety concerns because you've been dealing with them with multiple different iterations of the vaccines.”

Another example of vaccine platform manufacturing are the simian adenoviruses, which are potentially more immunogenic in humans. Variants of the simian adenovirus vaccine platforms were explored in 2014 during the Ebola outbreak and the high-priority diseases that the World Health Organization (WHO) identified.2

“Reducing the time to undertake clinical development is important,” noted Sarah C. Gilbert, PhD, professor of vaccinology at the Jenner Institute at the University of Oxford, in the United Kingdom, in an interview with Infectious Disease Advisor. “In many countries the approvals process for clinical trials is unnecessarily slow, introducing long delays. We need a more streamlined approach to clinical trial approvals.”

Global Threats, Global Cooperation

In a multinational effort, the United States along with the WHO continue surveillance of the next major outbreak.1,4 The WHO has identified priorities for researching vaccines4:

  • Crimean-Congo hemorrhagic fever
  • Ebola virus disease and Marburg virus disease
  • Lassa fever
  • Middle East respiratory syndrome coronavirus
  • SARS
  • Nipah and henipaviral diseases
  • Rift Valley fever
  • Zika
  • Disease X

Disease X is the unknown pathogen that is likely to be the world's next epidemic.4 The WHO acknowledged that this list needs to remain nimble as priorities would shift to Disease X from the existing known threats.4 Along with the WHO, another nongovernmental organization that seeks to develop vaccines to thwart the next epidemic is the Coalition for Epidemic Preparedness and Innovations (CEPI), a consortium of scientists, philanthropists, and investors that is not beholden to government or industry. CEPI seeks to plug the gaps among those of the government, industry, and nongovernmental organizations in vaccine development.3

Stanley A. Plotkin, MD, emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia, said in an interview with Infectious Disease Advisor that it is “too early to tell” how effective CEPI's efforts have been. He did, however, acknowledge an apex in the United States' preparedness: “basic research and vaccine development if the disease has interest by the military.”

What do all these vaccine advances have to offer the practicing clinician? “There are times when you have an outbreak that is going through the community and the private clinician is looking for an intervention for his or her patients,” explained Dr Fauci. “For the physician who is in the middle of an outbreak, he or she can now count on getting vaccines much sooner than he or she ordinarily would.”

Other Strategies to Combat Pathogens

Another innovation in vaccine development has been to create a broad-spectrum antiviral vaccine that would prevent RNA replication in several viruses rather than the “one-bug, one-drug approach” traditionally employed in disease prevention.5 One such example of this technology is the investigational favipiravir (T-705), an inhibitor of RNA

polymerase, which is being tested as an anti-influenza agent that also prevents replication of RNA viruses.5

Another broad-spectrum antiviral that shows activity against 15 viruses is the double-stranded RNA-activated caspase oligomerizer (DRACO) that causes apoptosis in cells with double-stranded RNA. Other examples of wide-ranging activity include UV4, which may be effective therapy for influenza and dengue fever, and has potential for viral hemorrhagic fevers, smallpox, and hepatitis.5

Viruses can now be quickly identified with rapid genomic sequencing, proteomics, and epigenomics.5 At point of care, genomic technology can rapidly discern which pathogen clinicians need to eradicate so they can avoid the empiric prescribing of antibiotics.5 Polymerase chain reaction (PCR) has enabled point-of-care detection to quickly identify the pathogen when symptoms are nonspecific and allows for contact tracing, as it did most recently in the Ebola outbreaks in West Africa.5

PCR testing at the point of care has allowed clinicians in resource-scarce regions to prescribe the right antibiotics while avoiding unnecessary antimicrobial therapy in patients with viral infections.5

In summary, the time from identifying the viral sequence of the pathogen in the pandemics of the last 20 years to phase 1 trials of vaccines has decreased dramatically. The key to rapid vaccine development lies in platform manufacturing, which uses an established process to shorten vaccine production.

References

  1. Graham BS, Mascola JR, Fauci AS. Novel vaccine technologies: essential components of an adequate response to emerging viral diseases. JAMA. 2018;319(14):1431-1432.
  2. Gilbert SC, Warimwe GM. Rapid development of vaccines against emerging pathogens: the replication-deficient simian adenovirus platform technology. Vaccine. 2017;35(35 Pt A):4461-4464.
  3. World Health Organization. List of Blueprint priority diseases. http://www.who.int/blueprint/priority-diseases/en/ Accessed May 18, 2018.
  4. Plotkin SA. Vaccines for epidemic infections and the role of CEPI. Hum Vaccin Immunother. 2017;13(12):2755-2762.
  5. Marston HD, Folkers GK, Morens DM, Fauci AS. Emerging viral diseases: confronting threats with new technologies. Sci Transl Med. 2014;6(253):253ps10.
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