NIH Researchers Call For Comprehensive Pandemic Preparations

A new essay from members of the National Institute of Allergy and Infecitous Diseases (NIAID) emphasized the need for biomedical research — in both domestic and international settings — in improving global pandemic preparedness.

The essay, authored by Hilary Marston, MD, MPH; Catharine Paules, MD; and Anthony Fauci, MD, from the National Institutes of Health’s (NIH) NIAID division, called for greater emphasis on learning the pathogenesis of infectious diseases in efforts to combat them.

Citing the original 1981 HIV/AIDS outbreak — then reported as Kaposi sarcoma and Pneumocystis carinii (P. jiroveci) pneumonia in once-healthy gay men — as a causation of international efforts to better prepare for pandemics through research, the authors noted similar public health actions leading to developments in a Zika virus treatment.

“Applying knowledge gained from work with dengue and other flaviviruses, researchers rapidly developed mouse models that recapitulate critical aspects of Zika infection, including replication and disease in the fetus,” researchers wrote. “These were subsequently used as surrogates to study congenital Zika syndrome.”

Researchers are now capable of using treatment such as monoclonal antibodies to neutralize Zika in the mouse models, according to the essay, and human trials are being considered.

It’s basic research portfolios that lead to countermeasure development, the researchers wrote. Vaccines, treatments, point-of-care diagnostics, and — in the event of arthropod-borne viruses — novel vector control are the results of initial research, and its progression towards action against pandemics.

In the realm of pathogens, researchers are often required, by limited resources, to prioritize advance countermeasure development “for microbes deemed most likely to emerge and cause significant morbidity and mortality.”

Such prioritization, as dictated by domestic indications or international guidelines such as the World Health Organization’s Research and Development Blueprint, is shaped by events such as the 2001 anthrax bioterror attacks, or the West Africa Ebola outbreaks from 2014 to 2016. The latter event led to the rapid development of phase 1 and field efficacy-tested vaccine candidates within a year of the outbreak, researchers wrote.

Researchers noted that swift timeline between outbreak and countermeasure clinical testing is being compressed even more so by organizations like the Coalition for Epidemic Preparedness Innovations. The organizations hope to do so by preparing potential vaccines “a priori for rapid evaluation in an outbreak.”

“These efforts are promising; however, their utility depends on predictive capability of the prioritization algorithm,” researchers wrote. “In the cases of HIV, SARS (severe actue respiratory syndrome), and Zika, no list or algorithm predicted their public health impact.”

Platform-based technology developers, conversely, focus on finding a relevant host immunogen, versus specific pathogens. Using vaccine platforms like viral vectors with genetic material coding for the immunogen would require preparation to develop the platforms themselves, which researchers noted would require more manufacturing capacity than in pathogen preparation.

Such a practice was used to develop vaccine candidates during the 2002 and 2003 SARS outbreak by the NIH and NIAID, among other agencies. The platform developed was a DNA plasmid with the SARS glycoprotein gene serving as the immunogen, researchers wrote.

“In addition to DNA, vaccine platforms include nanoparticles, virus-like particles, and mRNA, among others,” researchers wrote.

By filling research gaps to make platform candidates as efficient as possible, investigators could expedite the platform-based approach. This could be done through countermeasure research for prototype pathogens, researchers wrote, “understanding that the prototype may not emerge as a threat but assuming that techniques would be applicable to closely related microorganisms.”

Researchers noted that priority-pathogen lists may struggle to reflect the next threat, but prototype-pathogen strategy could take too long in the event of a pandemic.

“The most prudent path is to invest in research on all 3, bolstering the current ability to predict emerging infections, developing platforms that can be more rapidly adapted to new threats, and pursuing prototype-pathogen efforts to accelerate candidate development,” researchers wrote.

Such a comprehensive practice calls for industry, international, and community-based partnerships, and consideration to treatment solutions and diagnostics at an equivalence to vaccine preparation. Though it’s a tall order, researchers noted that infectious disease outbreaks will never cease.

“Whether dealing with HIV/AIDS, SARS, Ebola, Zika, or the inevitable unanticipated pathogen that will surely emerge, research has played and will play a critical role before, during, and after the outbreak,” researchers wrote. “Looking ahead, the biomedical research community must maintain its critical role in comprehensive pandemic preparedness.”

The essay, "The Critical Role of Biomedical Research in Pandemic Preparedness," was published online in JAMA this month.

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