Op-Ed: Why the US Must Move Beyond Its mRNA Monoculture

Editor's Note: The views an opinions expressed herein are solely those of the author and do not necessarily reflect those of BioPharm International, MJH Life Sciences, or its associates.

During the pandemic, US vaccine development surged on a wave of innovation and urgency. Yet, amid that success, the national strategy fell into a dangerous trap: an mRNA monoculture. Flush with funding, investors and policymakers came to view one platform as the universal answer to every vaccine challenge (1,2). That assumption is not only scientifically narrow, but strategically risky.

A monoculture problem

mRNA technology delivered COVID-19 vaccines at record speed, but its limitations are now apparent. Durability wanes, variants typically outpace vaccine updates, and tens of millions of immunocompromised and elderly Americans—those who need protection most—often mount weak or no immune response (3,4). Meanwhile, pathogens, such as Mpox, Zika, and hemorrhagic fever viruses, continue to spread globally, demanding tools that extend beyond mRNA’s capabilities (3,4).

As vaccine pioneer Stanley Plotkin observed, vaccine development should be “polytheistic, not monotheistic”(5). Building resilience in public health requires a diverse ecosystem of technologies—viral vectors, recombinant proteins, DNA, and next-generation multi-antigen platforms—suited to different threats and populations. The rapid elevation of mRNA as the perceived dominant platform following COVID-19 illustrates how a single-technology mindset can distort scientific and investment priorities.

Funding course-correction, not contradiction

The Department of Health and Human Services (HHS)’s recent recalibration of mRNA-focused funding is not a retreat from innovation. It is an overdue recognition that preparedness depends on portfolio balance. After 4 years of extraordinary investment in a single modality, HHS is now shifting resources to strengthen complementary platforms, offering potentially greater durability, broader variant coverage, and suitability for immunocompromised individuals (6).

In this context, the so-called “wind-down” of mRNA-specific programs does not contradict calls for diversity; it fulfills them. It represents an acknowledgment that America’s vaccine future cannot rest on a single technological pillar of hope.

Manufacturing and supply-chain resilience

Over-reliance on one platform also undermines supply-chain resilience. Key raw materials for mRNA vaccines come from a highly concentrated supplier base, with limited domestic redundancy, making the U.S. vulnerable to disruptions in global manufacturing and logistics, while U.S. stockpiles for orthopox still depend on a single foreign manufacturer (7,8). Diversifying platforms inherently diversifies production methods and suppliers, strengthening domestic manufacturing and biodefense readiness, key objectives across both Republican and Democratic administrations (9-11).

Restoring public confidence

Public confidence in vaccines erodes when success is defined by speed alone. The next era of vaccine development must focus equally on durability, accessibility, and trust. That means broadening investments, encouraging complementary technologies, and supporting manufacturers who can deliver scalable, continuous, made-in-America production for multiple threats, not just the next coronavirus variant.

Resilience through diversity

mRNA remains an essential part of the modern vaccine arsenal. But over-dependence on any single platform, in science, finance, or agriculture, breeds fragility. By rebalancing investment portfolios and procurement strategies, the US can move from a reactive to a resilient posture that rewards innovation across platforms and ensures preparedness for whatever biological challenge comes next.

Resilience demands diversity. The shift already underway at HHS is a step in the right direction as an acknowledgment that true innovation lies not in doubling down on what worked yesterday, but in building the plural toolkit our health security requires today.

References

1. U.S. Government Accountability Office. Operation Warp Speed: Accelerated COVID-19 Vaccine Development. Accessed Nov 25, 2025.
2. Coalition for Epidemic Preparedness Innovations. 2021 Annual Progress Report. Accessed Nov 26, 2025.
3. Tenforde, M; Self, W; Naioti, E; et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021. MMWR. 2021;70:1156-1162.
4. CDC. COVID-19 Vaccination Guidance for People Who Are Immunocompromised. Accessed Nov 25, 2025.
5. Plotkin, S; Robinson, J; Firtchett, J; Gershburg, E. Vaccine Development Should Be Polytheistic, Not Monotheistic. Clin Infect Dis. 2024;79(6):1518-1520.
6. Seitz, A. RFK Jr. Pulls $500 Million in Funding for Vaccine Development. APNews.com. Aug 6, 2025.
7. Seo, S; Song, M. Advancements and Challenges in Next-generation mRNA Vaccine Manufacturing Systems. Clin Exp Vaccine Res. 2025;14(4):299-307.
8. BavarianNordic. Annual Report 2024. Accessed Nov 26, 2025.
9. National Academies of Sciences, Engineering, and Medicine. Ensuring an Effective Public Health Emergency Medical Countermeasures Enterprise. 2021.
10. Administration for Strategic Preparedness and Response. 2023-2027 PHEMCE Multiyear Budget. Accessed Nov 25, 2025.
11. Bipartisan Commission on Biodefense. Biodefense in Crisis: Immediate Action Needed to Address National Vulnerabilities. Accessed Nov 25, 2025.