The COVID-19 pandemic highlighted both the transformative potential of mRNA vaccines and the structural challenges associated with their supply chains. Unlike traditional vaccine platforms, mRNA vaccines depend on highly specialized raw materials, including plasmid DNA (pDNA), nucleotides, enzymes, and lipid nanoparticles (LNP), that are produced by a limited number of global suppliers. These dependencies, combined with platform-specific manufacturing processes and stringent cold chain requirements, introduce vulnerabilities across production, distribution, and regulatory oversight. This narrative review examines the distinctive features of mRNA vaccine supply chains and identifies key challenges and opportunities across three interconnected domains: manufacturing systems, logistics and distribution, and regulatory governance. Drawing on literature published between January 2021 and March 2026, the review synthesizes evidence on supply chain bottlenecks revealed during the COVID-19 pandemic, including upstream raw-material dependencies, limitations in manufacturing scale-up, cold chain constraints, and regulatory fragmentation. Particular attention is given to the implications of these challenges for low- and middle-income countries, where infrastructure, technical capacity, and regulatory resources may limit participation in mRNA vaccine production and deployment. The review also highlights emerging strategies to strengthen supply chain resilience, including diversification of input suppliers, development of regional manufacturing hubs, improvements in vaccine thermostability, regulatory harmonization initiatives, and the use of digital technologies for supply chain management. By integrating insights from manufacturing, logistics, and regulatory perspectives, this study contributes to a better understanding of the structural characteristics shaping mRNA vaccine supply chains and identifies priority areas for strengthening global preparedness for future health emergencies.

In an effort to improve pandemic preparedness and health security, many low- and middle-income countries (LMICs) have launched initiatives to expand regional vaccine manufacturing. A number of elements relating to vaccine markets, production, value chains, and ecosystems significantly impact the ability to generate economically viable and sustainable vaccine manufacturing in LMICs. This paper provides an overview of vaccine manufacturing characteristics and global vaccine markets dynamics. Establishing vaccine manufacturing is a complex undertaking due to a variety of factors including intense competition, associated uncertainty regarding the ability to capture market share and substantial capital investment requirements. Substantive government commitment and investment are essential to ensure new local entrants compete successfully. In the medium to long run, the role of government should shift from supporting individual firms to strengthening local science ecosystems as this bolsters economic sustainability in three ways. First, investment in science promotes technological advances which can reduce production costs, e.g., through process innovations for vaccine manufacturing. Second, strong science ecosystems help to address the skills gap faced by manufacturers. And third, strong science ecosystems enable research and development of new vaccines that address local unmet needs and open new markets. Furthermore, developing a regional approach to vaccine manufacturing and procurement, with associated regulatory harmonization, is crucial to achieving economically viable and distributed vaccine manufacturing. Importantly, investment in research and development and fostering of regional collaborations drives innovation, feeding into new product discovery and consequently a strong pipeline of new vaccine products, driving economically sustainable regional vaccine manufacturing. This offers the potential to prevent endemic infectious diseases with significant socioeconomic and health burden or to develop therapeutic vaccines, generating regular interpandemic demand for regional vaccine manufacturers, consequently sustaining capacity retention and associated pandemic preparedness.

The global expansion of highly pathogenic avian influenza A (H5N1), particularly the clade 2.3.4.4b lineage, has renewed urgent concerns about its pandemic potential in the context of its ongoing panzootic expansion and increasing cross-species transmission. Despite decades of preparedness initiatives, critical technological and structural gaps persist, especially in low- and middle-income countries (LMICs), where both vaccine access and sustainable manufacturing capacity remain limited. In this perspective, we examine key lessons from past influenza pandemics and global preparedness strategies, including the Global Action Plan for Influenza Vaccines, highlighting persistent challenges related to sustainable manufacturing capacity and equitable vaccine access. Additionally, we examine the potential of messenger RNA (mRNA) vaccine platforms to address these limitations, given their rapid design, scalable manufacturing, and adaptability to emerging pathogens. Moreover, we examine the role of neuraminidase (NA) as a complementary antigen capable of broadening immune protection and reducing viral transmission. Finally, we describe recent advances in Latin America, focusing on Argentina’s participation in the mRNA Technology Transfer Programme co-led by the World Health Organization (WHO) and the Medicines Patent Pool (MPP), as a model for strengthening regional manufacturing capacity and contributing to global pandemic preparedness. Together, these elements indicate that effective H5N1 pandemic preparedness will require the integration of improved antigen design, flexible mRNA platforms, and sustainable regional manufacturing systems aligned with global procurement strategies.