DISCUSSION IN PROGRESS: The JPM CBRN Medical and the U.S. Department of Health and Human Services discuss preparations and responses to warfighter and public health threats during a panel session at the 2023 Biotechnology Innovation Organization International Convention. (Photo by Col. Matthew Clark, JPEO-CBRND JPM CBRN Medical)
VAMP program takes an agile approach to accelerate the delivery of vaccines against priority threats.
by Matthew Kuhn, Ph.D., Emily Cisney and Andrew Glenn
Dec. 11, 2020, was a momentous day for our nation. It was a day that signaled a hope for relief at the height of the COVID-19 pandemic as the U.S. Food and Drug Administration (FDA) issued the first emergency use authorization for a COVID-19 vaccine. A then little-known provision of the U.S. Code, 21 U.S.C. § 360bbb-3, emergency use authorizations have since become a household name in the fight against COVID-19.
But their utility reaches far beyond pandemic control.
The rapid response to the novel coronavirus pandemic revealed an ability of the pharmaceutical industry to rapidly address novel threats through the application of advanced vaccine technologies, then untested at commercial scale. Independently, many companies showed a capacity to pivot to a clear and present biological threat at a pace few believed possible.
There was a need for a new program capable of working with such companies to advance the next generation of vaccines for the warfighter on a time scale that can meet both current and future threats head on.
Vaccine Acceleration by Modular Progression (VAMP), a program within the Joint Project Manager for Chemical, Biological, Radiological and Nuclear Medical (JPM CBRN Medical) as of 2021, was created for this very purpose. The program facilitated the establishment of agreements this past fall and winter with eight pharmaceutical leaders, targeting over 15 biological warfighter threats, to bring vaccines to Phase I clinical trials and beyond, all within the next five years. But VAMP represents more than just the sum of eight candidate vaccines; it demonstrates a new approach to vaccine development through a stepwise, modular method in which DOD can advance vaccine development at the speed of relevance through partnerships with government agencies and performers with a record of proven performance.
THE NEED ARISES
As the COVID-19 pandemic unfolded, a program management team at JPM CBRN Medical, a component of the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), focused on the development and acquisition of medical solutions to combat CBRN threats, took note of the criticality of rapidly manufactured vaccines in battling the pandemic, and the distinctive value emergency use authorizations provide in an emergency situation. The program management team forecasted that this invigorated requirement for rapid advancement of vaccines in times of acute need was applicable to DOD in rapidly pivoting biological defenses for the warfighter and the nation in response to emerging and novel threats.
A team of program managers, scientists, lawyers and contracting officers set in motion a flexible contracting strategy that could accept funding and move quickly to support development of new vaccines. Additionally, the team utilized its established partnership with the Office of the Deputy Assistant Secretary of Defense for Chemical and Biological Defense to begin messaging essential investment and identification of enhanced biodefense and pandemic preparedness funds.
When JPM CBRN medical leaders returned to their DOD roles after details to positions with Operation Warp Speed and other critical COVID-19 responses, they brought with them the lessons learned from their front row seats to the twists and turns of the pandemic and our nation’s public health response. Such lessons came on the heels of shepherding several medical countermeasures into pivotal Phase III clinical trials and ultimately, emergency use authorizations at a never-before-seen pace.
The question was, could DOD build off this experience to similarly address priority threats to the warfighter? Supporting vaccine development toward FDA licensure can be a long process, but the response to COVID-19 rebuked this narrative. The pandemic revealed that full FDA licensure is not necessary to get shots in arms when circumstances permit. If success hinged on emergency use authorizations rather than full licensure, how rapidly could DOD move?
To accelerate advanced research to the necessary pace, the development of partnerships with other government agencies was indispensable, as demonstrated by the relationships built during Operation Warp Speed and previous interagency coordination. JPEO-CBRND continues to strengthen its relationship with the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA), and with other DOD agencies, such as the Defense Innovation Unit.
As an interagency partner, BARDA contributes both funding and technical expertise to the VAMP program. Collaborating with BARDA allows the program to tap into a vast array of experts in vaccine design, manufacturing, testing and regulatory navigation, all of which are essential to maintaining an efficient program. A new partnership with the Defense Innovation Unit, which will leverage its accelerated contracting process, will allow VAMP to rapidly seek out and contract innovative biotechnology companies to provide cutting-edge medical capabilities.
COMING TOGETHER: JPM CBRN Medical, BARDA and UTMB personnel during a UTMB site visit. (Photo by Sarah Murtaza, BARDA)
VAMP FOUNDATIONS
Moving at an accelerated pace and maintaining the latitude to address emerging biological threats requires an acquisition approach that values nontraditional defense contractors with significant expertise in vaccine manufacturing. It also requires the development of system-of-systems technologies that move beyond the “one-bug-one-drug” dogma, the incorporation of a mechanism to consistently review progress, and be ready and willing to end efforts that underperform and easily pivot to the next candidate in line.
These pillars underpin the VAMP program and its use of the other transaction authority for prototype projects to enter into agreements with nontraditional defense contractors for rapid vaccine development.
Other transaction authority has provided a consistent capability to provide basic, applied and advanced research for decades. Although originally required to be directly relevant to weapons or weapon systems, other transaction authority agreements for prototype development can now be created for any effort directly relevant to enhancing the mission effectiveness of military personnel and the support or improvement of platforms, systems, components or materials. Vaccines are a prime example of meeting this need by developing vaccines toward lethal pathogens that lack medical countermeasures and are largely unmitigated risks to warfighter readiness and effectiveness. These vaccines are intended to provide an additional layer of protective defense, regardless of natural or intentional threat exposure, augmenting the warfighter’s biological armor against such threats.
PLATFORM DEVELOPMENT
Lessons learned from Operation Warp Speed continued to influence the VAMP program as it undertook the selection of performers. Namely, that when it comes to vaccines, there is no single-best technology for vaccine design; the best technology is the one that works for a given threat. A second motif during selection was that designing novel vaccines one at a time from scratch cannot keep up with the speed of nature. A balance of cutting-edge technologies and tried-and-true vaccine backbones were selected for further development. However, the foundational concept shared by all VAMP performers is an emphasis on vaccine platform technologies creating system-of-systems prototypes.
Vaccine platforms act as the rolling body and turret of a tank. As tanks are produced, the body and turret largely remain the same, and can be deployed to counter an array of battlefield threats. Different threat-specific ordnance (e.g., armor piercing, high explosive) can then be selected to address each individual target, without changing the overall design of the tank. For vaccine platforms, the basic vaccine components and antigen carrier of the platform remain the same regardless of threat, just like the body and turret of the tank. Similar to threat-specific shells, the antigenic design of platforms, or the pieces of the vaccine construct that train the immune system on what to prepare for, can be modified to target-specific threats without changing overall vaccine design.
Just like platform vaccines support the insertion of various antigens to target differing threats, the system of systems that make up a platform vaccine can support interchangeability of various vaccine components to optimize a vaccine for a specific use. For example, deliberate alteration of the delivery method of a vaccine can tailor use for warfighter needs by allowing easier vaccine administration, or through improvement of cold chain storage and stability.
Although each performer will design and test a candidate vaccine for a specific threat or threat family, the overall objective of the program is to advance the underlying platforms and systems upon which the vaccine is built for DOD to employ as part of the warfighter’s complete biological armor. The performers with whom agreements were recently awarded represent a diversity of platform technologies.
- Traditional Vaccine Platforms:
- Modified Live Attenuated Vaccine: Bavarian Nordic A/S will modify its BN-MVA platform vaccine, the backbone of the FDA-approved JYNNEOS smallpox vaccine and mainstay of the nation’s strategic national stockpile, for prevention of three equine encephalitis viruses (Venezuelan, Eastern and Western).
- mRNA: The University of Texas Medical Branch (UTMB), in partnership with Moderna Inc., will build on their success in developing a bivalent COVID-19 vaccine by applying their mRNA platform to hemorrhagic fever viruses, including Ebola Zaire, Ebola Sudan, Marburg and Lassa fever viruses. Additionally, AstraZeneca will further develop its mRNA platform for protection against pandemic avian influenzas.
- saRNA: Two efforts, the Access to Advanced Health Institute and UTMB in partnership with HDT Bio, will further develop self-amplifying RNA (saRNA) vaccines, a more recently developed technology, against pandemic avian influenzas, henipaviruses and Crimean Congo hemorrhagic fever virus. saRNA vaccines aim to improve the immune response to mRNA vaccines while increasing their safety profile.
- Immune Modulator Platforms:
- Cytosine-Phosphate-Guanosine Oligodeoxynucleotide: Dynavax Technologies will conduct a Phase II human clinical trial with its novel immune modulator platform cytosine-phosphate-guanosine 1018, a toll-like receptor agonist, co-administered with DOD’s Plague Vaccine rF1V, to improve the utility of the plague vaccine for rapid response.
- Toll-like Receptor Agonists: ENA Respiratory and the Access to Advanced Health Institute are independently developing a self-administered dry powder nasal spray for the prevention of common and emerging respiratory viral threats. Both products are designed for rapid protection and use in austere environments.
The utilization of platforms significantly reduces development time for future efforts by altering only minor portions of vaccines to address new targets. By targeting development of proven platforms, the program supports the creation of an agile pharmaceutical industry with the tools and technologies necessary to rapidly shift design and manufacturing of vaccine candidates from current to emerging threats, in near-real time.
TEAMWORK: JPM CBRN Medical, BARDA and HDT Bio personnel during an HDT Bio Corporation site visit. (Photo by Winnie Wong, HDT Bio Corporation)
DELIBERATE DECISIONS POINTS
The final and most pertinent enabler for VAMP’s agility and speed is its purposeful modular contracting strategy. VAMP incorporates go/no-go decision checkpoints in each agreement throughout the development and licensure process. The go/no-go decision checkpoints are mutually agreed upon measures of performance between the government and the performer. These measures set expectations, and should a performer not meet the threshold criteria (or do so significantly behind schedule), the agreement may be terminated, followed by selection of a new performer.
When combined with optional work built into the agreements, VAMP is enabled to advance the development of vaccine prototypes to reach full or interim capabilities. The flexible contracting approach employed by VAMP empowers the ability to fail smart and pivot to maintain a steady flow of technologies, or to address emergent needs related to nascent biological agents of interest.
By pursuing agreements through other transaction authorities, the program can carry out go/no-go decision-making and significantly reduce the risk inherent in vaccine development by pursuing those platforms showing promise and shifting away from those that require more extensive troubleshooting. Over the long term, this method will offer opportunities for a wide range of performers to prove themselves and their products while maintaining a relatively discrete program budget.
Although it may seem that a significant risk to cost and schedule remains when an agreement is terminated and a new performer selected, VAMP is deliberate in selection of performers, identifying those with a proven track record of manufacturing capabilities and positive evidence of prior platform use. As manufacturing is one of the most risk-intensive aspects of vaccine development, taking this focus early in performer selection mitigates much of this risk.
CONCLUSION
The VAMP program’s success is highly contingent on not just selecting performers with the most promising vaccine candidate, but those with the technology and expertise to develop vaccine platforms that fit with the goals and structure of the program. This will require careful vetting of performers and meticulous expectation-setting to achieve mutual benefit.
Through interagency coordination, multiple risk-mitigation measures and creative contracting, the program aims to shift the vaccine development paradigm. Establishing prototype project agreements for vaccine platform technologies while applying the system-of-systems approach allows the program to pivot and respond to emerging threats and unique requirements for warfighter use. VAMP takes an agile and “fail forward and pivot” approach to accelerate the delivery of interim and full capabilities against priority threats. Drawing from the successes and lessons learned from the nation’s response to the COVID-19 pandemic, the Vaccine Acceleration by Modular Progression program facilitates DOD’s dedication to enhancing the warfighter’s biological body armor with a dependable layer of protection against further current and emerging biological threats.
For more information, go to https://www.jpeocbrnd.osd.mil/.
MATTHEW KUHN, PH.D., is a bioengineer supporting the VAMP program and a trained large animal veterinarian. He earned his Ph.D. in immunology, Doctor of Veterinary Medicine and B.S. in animal science from Michigan State University.
EMILY CISNEY is an assistant program manager for the VAMP program and a previous medical laboratory technologist at U.S. Army Medical Research Institute of Infectious Diseases. She has previously served as a program manager at the Military Infectious Disease Research Program and the Armed Forces Health Surveillance Branch’s Global Emerging Infectious Disease Surveillance program. She earned a Master of Public Health from John Hopkins Bloomberg School of Public Health and a B.S. in biology from Shippensburg University.
ANDREW GLENN is the deputy joint product manager for JPEO-CBRND’s advanced defense pharmaceuticals medical countermeasure development program. He earned an M.S. in biotechnology from Johns Hopkins University and a B.S. in biotechnology from James Madison University. He holds the DAWIA Advanced certification in program management.
CONTRIBUTORS:
Lucy Ward, Ph.D., senior scientist, JPEO-CBRND Advanced Defense Pharmaceuticals (ADP); Lt. Col. Amanda Love, former joint product manager, JPEO-CBRND ADP; and Lt. Col. Patrick “Race” Dulin, joint product manager, JPEO CBRND ADP.
