mRNA vaccines and therapeutics beyond COVID-19: A review of the global clinical development landscape, low- and middle-income countries involvement and relevance to their contexts

ABSTRACT

mRNA vaccines demonstrated transformative potential during the COVID-19 pandemic, yet global access to mRNA research, development, and manufacturing capacity remains unequal. This review systematically maps the global mRNA clinical development landscape beyond COVID-19, based on publicly available sources. A total of 244 vaccine and therapeutic candidates were identified: 123 targeting 23 communicable diseases and 121 targeting 69 non-communicable diseases, including 102 cancer-focused candidates. Two hundred and twenty-seven candidates (93%) were in early clinical development phases and 12 in late-stage development. Eighty-five developers (50 companies, 35 institutes/hospitals) are engaged in this space. Low- and Middle-Income Countries (LMICs) participation was limited to 57 candidates, primarily in upper-middle-income countries. This study reveals a rapidly expanding pipeline for diverse diseases, many aligned with LMIC public health priorities, yet with limited LMIC participation. Equitable inclusion, and collaborations are vital for sustainable global development. This study could inform future LMIC-led mRNA development and manufacturing initiatives.

Introduction

The COVID-19 pandemic marked a significant milestone in medical science with the development and deployment of mRNA vaccines, such as those of Moderna and Pfizer-BioNTech, which offered a rapid and highly effective tool for addressing a major public health threat.^1–3 However, significant challenges emerged in the distribution of COVID-19 vaccines, as most supplies were secured by high-income countries (HICs), while low- and middle-income countries (LMICs) faced limited access.⁴ This situation highlighted global health inequities and emphasized the necessity for more sustainable and equitable access solutions, alongside strengthening local vaccine development and production capacity in LMICs, including mRNA-based vaccines, to ensure self-reliance and readiness for future pandemic responses.^5,6 To respond to these needs multiple global vaccine manufacturing initiatives promoted by public and private organizations and focused on LMICs have emerged, such as: the WHO – MPP mRNA Technology Transfer Programme, launched in 2021, that created a global network of 15 LMIC manufacturing partners and supported the development and transfer of an mRNA technology platform, using COVID-19 as proof of concept pathogen, with the objective to establish sustainable manufacturing capacity and capability for future mRNA-based products, advance research on mRNA-based vaccines and therapeutics (e.g., human immunodeficiency virus (HIV), tuberculosis (TB), Dengue, Respiratory Syncytial Virus (RSV)) and sustainable regional production (e.g., local production of new lipids, enzymes, and other reagents) and ultimately enhance pandemic response readiness⁷; the Regionalized Vaccine Manufacturing Collaborative (RVMC) and the UK-funded Future Vaccine Manufacturing Research Hub (Vax-Hub) further aiming to create regional ecosystems and address barriers to local production^8,9 of vaccines manufactured through different platforms, including mRNA; the partnerships of CEPI with BioNTech to develop an mRNA manufacturing facility in Rwanda,¹⁰ with Moderna and BioFarma under the 100 d Mission to accelerate mRNA vaccine development,^11,12 and with DNA Script to advance a new technology that could streamline the production of mRNA-based vaccines. Collectively, these initiatives seek to reduce inequities, foster local capacity, and ensure rapid response to future pandemics.

Interestingly, the mRNA technology platform offers a novel approach to treat a wide range of diseases, including both communicable diseases (CDs) and non-communicable diseases (NCDs), as well as immune-related and nonimmune-related conditions.^13–15 Recent publications^16–18 provide insights and representative examples of various applications of the mRNA technology for CDs and NCDs, showcasing the potential and the accelerated and strategic mRNA platform advancements. This broad range of applications represents an opportunity for LMICs, enabling manufacturers to leverage the investment made in building mRNA capacity by responding to national/regional health needs whilst opening avenues for sustainable revenue generation through the commercialization of locally relevant products. In fact, while CDs such as HIV, TB, and malaria¹⁹ continue to pose a significant health burden in LMICs, these countries are also experiencing an epidemiological transition resulting in a growing morbidity and mortality burden attributable to NCDs, particularly cancers, diabetes, cardiovascular, and respiratory diseases.²⁰

This article presents the results of a comprehensive and systematic landscaping of mRNA-based vaccine and therapeutic candidates (V&TCs) in clinical development, conducted as part of the WHO – MPP mRNA Technology Transfer Programme in order to identify V&TCs of potential interest to LMIC manufacturers and promote co-development and licensing opportunities tailored to country/regional epidemiological needs and commercial opportunities. The presented analyses include a multi-parameter breakdown of the global mRNA vaccine candidate pipeline beyond COVID-19, an assessment of the level of inclusion of LMICs in current clinical development projects and an evaluation of candidates’ relevance from a public health perspective, particularly in terms of their alignment with LMIC epidemiological priorities.

Methods

V&TCs identification and classification

This study employed a structured, multi-parameter approach to identify and analyze mRNA-based V&TCs under clinical development and targeting both CDs and NCDs. A flowchart illustrating the search strategy and the process for collecting, screening, and evaluating mRNA trials, and identifying V&TCs is presented in Figure 1. The methodology comprised two main components:

Figure 1.

Study dataset flow chart. The flowchart illustrates the stepwise approach used to identify, select, and classify clinical trials investigating mRNA-based V&TCs.

Clinical trials identification and shortlisting

An initial keyword-based search (Step 1) was conducted across global database registries such as ClinicalTrials.gov,²¹ Beacon Intelligence,²² WHO (International Clinical Trials Registry Platform (ICTRP)),²³ Australian New Zealand Clinical Trial Registry (ARCTN),²⁴ ChiCTR,²⁵ EU-Clinical Trials Information System (CTIS),²⁶ EU Clinical Trials Register (EUCTR),²⁷ Clinical Trials Registry – India (CTRI),²⁸ German Clinical Trials Register (DRKS),²⁹ The UK Clinical trial registry,³⁰ and The Netherlands OMON (NL-OMON),³¹ to identify relevant mRNA vaccine clinical trials (see also list in Supplementary Excel S1). The search strategy combined terms using Boolean operators (AND, OR), with truncations applied where appropriate. The primary search queries included: “mRNA vaccine,” “mRNA therapy,” “RNA vaccine,” “RNA therapy,” and “nucleic acid vaccine.” A broad secondary search queries targeted multiple disease categories (including CDs, cancer types, genetics, autoimmune, metabolic, and respiratory disorders) and their subtypes, in combination with “RNA vaccine/therapeutics.” The dataset was extracted and downloaded from the database registries in comma-separated value (.csv) format, reflecting the status and information up to March 1, 2025. Complementary searches (Step 2) were performed afterward to identify additional trials referenced in reviews^13,32,33 and original articles, and monitoring of corporate communications was conducted to detect newly disclosed or discontinued trials. Each entry was manually reviewed to ensure its relevance and alignment with the scope of the analysis. All the 6149 clinical trials were classified by “study type” as either interventional or observational, based on the classification in the original database registries or manuscripts. A series of exclusion criteria was applied to retain only active interventional studies at the clinical development stage in which mRNA-based candidates were the primary intervention, resulting in the exclusion of 5572 clinical studies. As the study focused beyond COVID-19, trials assessing monovalent mRNA COVID-19 vaccines or mRNA-based booster vaccinations were excluded (n = 278), unless they also targeted other diseases, either concomitantly or in combination. The application of all the above-mentioned criteria resulted in a final clinical trial dataset including 299 unique studies, 117 targeting CDs, and 182 NCDs.

Data analysis: V&TCs identification and data visualization

The 299 trials in the final dataset were analyzed and reclassified based on the mRNA V&TC under clinical evaluation, resulting in a total of 244 unique candidates. The candidates and associated details (e.g., clinical trial number(s), disease indications, developer, latest clinical trial phase, route of administration, delivery system) were all compiled in an Excel spreadsheet (Supplementary Excel S1). Finally, each mRNA V&TCs was analyzed based on the available technological information to assign a degree of personalization and functionality. The V&TCs classification based on the degree of personalization of the mRNA and of the delivery technology used was: “generalised” candidates, off-the-shelf products including an mRNA encoding nonspecific antigens using delivery systems primarily lipid-based; “semi-personalised” mRNA candidates encoding nonspecific antigens, adopting an autologous or allogenic delivery system (e.g., dendritic cells); and “personalised” mRNA candidates, encoding patient-specific antigens (typically neoantigens or tumor specific antigens), independent of the delivery system (generalized or personalized). Functionality was classified as: “Preventive vaccine candidates,” designed to induce an immune response protecting individuals against a future disease; “Therapeutic vaccine candidates,” eliciting an immune response against an existing disease; and “Therapeutic candidates,” delivering an immunomodulator that modulates immune response without generating an antigen-specific immune response. Taken together, these classifications enabled a more refined assessment of the mRNA pipeline using multi-parameter graphical interfaces, as presented in the results section.

Global burden of disease data extraction and classification

To evaluate the candidates based on their epidemiological relevance in LMICs, global disease epidemiology data for incidence, prevalence, and disability-adjusted life years (DALYs) were extracted from the 2021 Global Burden of Disease (GBD) database for both CDs and NCDs.^34–36 Each country was classified according to the 2024 World Bank Classification: high-income countries (HICs), upper-middle income countries (UMICs), lower-middle-income countries (LoMICs), and low-income countries (LICs).³⁷ Disease-specific data for LICs, LoMICs, and UMICs were aggregated into a single low- and middle-income country (LMIC) group, while data for HICs were aggregated into a separate group. The GBD data for HICs and LMICs were subsequently independently ranked (from highest to lowest) for incidence, prevalence, and DALYs (Supplementary Excel S2).

Each V&TCs target disease was matched to its corresponding GBD category, and the number of V&TCs under development for each disease was mapped in the disease burden ranking (Supplementary Excel S2). For diseases without a direct GBD equivalent, their main clinical manifestation was matched with the closest GBD category (e.g., RSV with lower respiratory infections; uveal melanoma with other eye cancers).

Results

Data overview

As of March 1, 2025, a total of 244 unique mRNA V&TCs were identified using the defined set of inclusion and exclusion criteria (Figure 1 and Methods section). These candidates were extracted from an initial shortlist of 299 active clinical trials by identifying and consolidating unique candidates present in more than one trial.

As shown in Figure 2(a), the V&TCs (n = 244) were categorized into two categories: those targeting CDs (n = 123, 50%), including viral, bacterial, or parasitic infections, and those targeting NCDs (n = 121, 50%). Within the NCD category, cancer was the predominant focus, accounting for 102 out of the 121 V&TCs (84%). The remaining 19 NCD V&TCs (16%) targeted conditions such as cystic fibrosis, cardiovascular diseases, and other genetic or metabolic disorders.

Figure 2.

Global landscape of mRNA-based V&TCs under clinical development by disease area. (a) Total number ofcandidates for communicable diseases, non-communicable diseases (cancer), and non-cancer non-communicable diseases. (b) Total number of clinical trials, targeted diseases, total V&TCs, highest clinical phase reached, developers, degree of personalization, functionality intent and number of candidates tested in LMICs, by disease area.

Figure 2(b) summarizes the distribution of these V&TCs across key parameters, including the number of clinical trials, disease targets, developers, most advanced trial phase reached, degree of personalization, functionality intent and extent of clinical testing in LMICs. Detailed distribution of V&TCs by highest clinical phase reached and additional multi-parameter breakdowns by delivery system, degree of personalization, and administration route for CDs and NCDs are shown in Supplementary Figure S1 and Figures S2a and S2b, respectively.

Overall, the CD-targeting candidates (N = 123) addressed 23 distinct etiologic agents; 60 candidates (49%) were undergoing Phase I clinical trials, 48 (39%) were in Phase I/II, eight (7%) in Phase II, and the remaining seven (6%) were in late development phase (Phase III) (see also Supplementary Figure S1). According to the degree of personalization of the mRNA and of the delivery technology used (i.e., generalized, semi-personalized, and personalized as defined in the Methods section), most candidates targeting CDs were classified under the generalized category (n = 119, 97%) (Supplementary Excel S1). In addition, analysis by functional intent showed that 118 CD V&TCs (96%) were designed for preventive use. The remaining five candidates were therapeutic, including four semi-personalized products targeting HIV (n = 3) and hepatitis B virus (HBV, n = 1), and one generalized therapeutic candidate targeting HIV.

The NCD-targeting candidates (N = 121) were directed against 52 cancer types and 17 additional non-cancer NCDs; 51 candidates were undergoing Phase I clinical trials (42.1%), 40 (33%) were in Phase I/II, 20 (17%) in Phase II, and five (4%) in the late phases (Phase II/III, and III). Phase information was unavailable for five NCD candidates (4%) (see also Supplementary Figure S1). Among NCD candidates, only 44 (36%) were generalized, with the remainder adopting more tailored approaches 43 (36%) semi-personalized and 34 (28%) fully personalized). Notably, within the semi-personalized group, a small subset (n = 6) utilized allogeneic cells as a delivery system (Supplementary Excel S1). No preventive vaccine candidates were identified for NCDs, where all candidates were intended for therapeutic use.

V&TCs distribution by disease indication

As shown in Figure 3(a), the breakdown of the candidates by disease indications revealed that, among the CD V&TCs (n = 123), seasonal influenza accounted for the largest number of candidates (n = 49, 39%), followed by HIV (n = 15, 12%), RSV (n = 15, 12%), and pandemic influenza (n = 9, 7%), with the remaining 44 candidates targeting other CDs. Notably, within the CD pipeline, candidates for seasonal influenza (n = 4, including two in combination with COVID-19), RSV (n = 1), cytomegalovirus (CMV) (n = 1), and norovirus (n = 1) had progressed to Phase III.

Figure 3.

Distribution of mRNA-based V&TCs under clinical development across (3a) communicable and (3b) non-communicable diseases. Superscripts indicate if the diseases were included in the WHO global endemic pathogens priority list³⁸ and/or targeted within clinical trials in LICs, LoMICs, or UMICs.

Within NCD cancer V&TCs (n = 102) (Figure 3(b)), analysis of clinical trial data by disease subtype revealed that melanoma, non-small cell lung cancer (NSCLC), glioblastoma/glioma, pancreatic cancer, and breast cancer were the predominant targets, collectively accounting for 72% (n = 73) of candidates. Overall, three candidates had progressed up to Phase III (one targeting various solid tumors, one specific for NSCLC, and one targeting uveal melanoma) while 15 had reached Phase II.

Figure 3.

(Continued).

Non-cancer NCD V&TCs (n = 19) (Figure 3(b)), which targeted genetic disorders (e.g., cystic fibrosis) and inflammatory disorders (e.g., systemic lupus erythematosus, myasthenia gravis), comprised five candidates that had progressed to Phase II trials.

V&TCs distribution by developer

Comprehensive analyses were conducted to provide strategic insights into the mRNA candidate landscape currently under clinical evaluation (Figures 4 and 5). These analytics examined the dataset from two perspectives: (1) disease-to-developer, and (2) developer-to-disease.

Figure 4.

mRNA V&TC pipeline for communicable diseases. (a) Disease-to-developer view. Shows the relationship between disease targets and developers. Each branch represents a developer; bar height indicates the highest clinical phase reached. Numbers in brackets show candidates per developer per disease. (b) Developer-to-disease view. Shows each developer and their disease targets. Each branch represents a disease; bar height indicates the highest clinical phase. Numbers in brackets show candidates per disease.

Figure 4.

(Continued).

Figure 5.

mRNA V&TC pipeline for non-communicable diseases. (a) Cancer, disease-to-developer view. Shows the relationship between disease targets and developers. Each branch represents a developer; bar height indicates the highest clinical phase reached. Numbers in brackets show candidates per developer per disease. (b) Cancer, developer-to-disease view. Shows each developer and their disease targets. Each branch represents a disease; bar height indicates the highest clinical phase. Numbers in brackets show candidates per disease. (c) Other non-cancer non-communicable diseases, disease-to-developer view. Shows the relationship between disease targets and developers. Each branch represents a developer; bar height indicates the highest clinical phase reached. Numbers in brackets show candidates per developer per disease. (d) Other non-cancer non-communicable diseases, developer-to-disease view. Shows each developer and their disease targets. Each branch represents a disease; bar height indicates the highest clinical phase. Numbers in brackets show candidates per disease.

Figure 5.

(b) Cancer, developer-to-disease view. (Continued).

Figure 5.

(c) Other non-cancer non-communicable diseases, disease-to-developer view. (Continued).

Figure 5.

(d) Other non-cancer noncommunicable diseases, developer-to-disease view. (Continued).

In the disease-focused analysis, each disease was mapped to the developers pursuing corresponding V&TCs. Within the CD category (Figure 4(a)), this mapping revealed that seasonal influenza, pandemic influenza, RSV, HIV, and varicella-zoster virus were the most targeted, attracting the highest number of developers (n = 18), including global pharmaceutical companies, research institutions & hospitals, and co-developing initiatives. For NCDs, Figure 5(a,c) summarize disease-to-developer analytics for cancer and other non-cancer conditions, respectively. The mapping revealed that organ-specific cancers (melanoma, breast cancer, glioblastoma/glioma, NSCLC, pancreatic cancer, gastric cancer, and colorectal cancer) were collectively targeted by the highest number of developers (n = 38). Among non-cancer NCDs, cystic fibrosis stood out as the most frequently targeted condition, with four dedicated developers.

In the developer-to-disease analysis, V&TCs were mapped by developer. Within CDs, Moderna emerged as the leading developer with a total of 17 distinct disease targets, followed by BioNTech (alone or in collaboration with Pfizer) with six and Sanofi with five. GSK and Pfizer maintained a more limited disease portfolio (Figure 4(b)). Notable key developers in the NCD space included Moderna, BioNTech, Arcturus, Myeloid, Duke University, Antwerp University, and Radboud University, each associated with various cancer and non-cancer NCD targets (Figure 5(b,d)).

As shown in Supplementary Figures S3 and S4, across the entire dataset, the majority of V&TCs were developed by companies, ranging from large multinational corporations to small biotech firms (61% in CDs and 44% in NCDs). Institutes, universities, and hospitals were more engaged in NCD V&TCs development (38% of candidates) than in the infectious disease space (22% of CD candidates). Some V&TCs (17% in CDs and 18% in NCDs) were developed through collaborations among companies, noncommercial organizations, or between companies and institutes.

Overall, companies, particularly multinational corporations with large development portfolios, dominated development, with Moderna leading in the number of candidates (55 V&TCs: 44 CDs, three cancer-NCDs, five other NCDs, and three co-developments in NCDs). Duke University emerged as the most active academic institution (nine V&TCs: three CDs, including two collaborations, and six cancer-NCDs, including one collaboration). Out of 85 developers/development collaborations identified, only six international companies (namely Moderna, Sanofi, BioNTech, CureVac, Arcturus, and Argos), and two organizations (Duke University and NIAID), were active in both the CD and NCD space.

Interestingly, 61% of V&TC candidates (N = 149), 47% of CD candidates (N = 116) and 14% of NCD candidates (N = 33), were based on Lipid Nanoparticle (LNP) formulations, originating from 36 distinct developers or development collaborations (Supplementary Figure S2; Supplementary Excel S1). Based on publicly available information, only some developers – such as Moderna, Arcturus, and NIAID – apply their formulation technology as a platform, maintaining a consistent lipid nanoparticle (LNP) composition across multiple candidates (see Supplementary Excel S1).

V&TCs and LMICs

The level of involvement of LMICs in clinical development was evaluated by assessing in which countries the clinical trials were carried out. As shown in Figures 2(b) and 3(a,b) and detailed in the Supplementary Excel S1, overall, 57 V&TCs (23%) were tested in LMICs. Supplementary Figures S5a and S5b show the 19 countries where these 57 V&TCs were under clinical evaluation: three LICs, three LoMICs, and 13 UMICs. Among UMICs, China, South Africa, and Argentina hosted most of the trials, with 38 V&TCs tested in China, 11 in South Africa, and eight in Argentina. Nineteen of the 57 V&TCs (33%) targeted six different communicable diseases (influenza, TB, HIV, RSV, hMPV, and HBV), 10 of which were tested in South Africa, representing 91% of all V&TCs tested in the country. The remaining 37 V&TCs (67%) targeted 32 cancer types, and one targeted a non-cancer NCD. Notably, 34 of the 38 V&TCs tested in China targeted NCDs.

Global disease burden metrics in HICs and LMICs for CDs and NCDs were assessed to understand how well the clinical development pipeline of mRNA V&TCs aligned with LMIC-specific disease priorities (Supplementary Excel S2).

The classification of CDs in the GBD often includes only clinical syndromes (e.g., upper, and lower respiratory tract infections, otitis media) without specifying the underlying etiological agents. This limitation complicated the assessment of the adequacy of the current CD development pipeline for the specific needs of LMICs, as the mapping of the V&TCs to GBD CD categories required some approximation (see Methods section). To further address this point, the 2024 list of the 17 WHO global priority pathogens for vaccine research and development for the Immunization Agenda 2030³⁸ was cross-checked against the list of the CDs targeted by the V&TCs. Seven of the 17 WHO priority pathogens were among the 23 CDs with candidates under clinical development (Figure 3(a)).

The same assessment for NCDs indicated that the pipeline broadly reflected the NCD burden in LMICs, particularly for cancers, when considering incidence, DALYs, and prevalence. Candidates under development for other NCDs primarily targeted endocrine, metabolic, blood, and immune disorders (n = 10), as well as other chronic respiratory diseases, such as ciliary dyskinesia and cystic fibrosis (n = 5), for which specific data were unavailable.

Discussion

This review offers an in-depth profiling of mRNA V&TCs across key parameters, including developer landscape, disease indications, clinical trial phases, and technological attributes. To the best of our knowledge, this study is the first comprehensive and systematic global landscape review of mRNA V&TCs undergoing clinical evaluation. While recent publications have begun to explore mRNA applications for specific diseases,^1,2,33 such as CDs beyond COVID-19^13,39 and selected cancer¹⁴ types, this review presents a unique, holistic overview, encompassing all disease indications beyond COVID-19, including both CDs and NCDs.

The distribution of mRNA V&TCs appears balanced across CDs and NCDs as well as across clinical development phases, aligning with the overall global trial landscape, which remains skewed toward early-stage development. This pattern may also reflect the substantial increase in trials initiated during or after the COVID-19 pandemic, when the approval of the first mRNA vaccine spurred a rapid expansion of mRNA research and development across multiple disease areas (data not shown; Figure 2(b), Supplementary Figure S1).

The analysis also shows distinct developmental trajectories for V&TCs addressing different disease categories.

Most of the V&TCs under development targeting CDs are preventive vaccines employing a generalized (i.e., not personalized) mRNA and delivery strategy, predominantly based on LNPs. This is not unexpected, as these candidates are designed as off-the-shelf interventions suitable for broad application across patient populations and for mass or targeted immunization campaigns (Figures 2(b) and S2a). In addition, most of the CDs’ V&TCs targeted viral diseases, where high efficacy is most likely achievable with a single antigen or a cocktail of a few antigens/antigen variants. Several of the viral disease candidates identified in this analysis, including those targeting pandemic influenza, RSV, Nipah virus, and Chikungunya, correspond to pathogens listed by WHO and CEPI as having epidemic or pandemic potential.⁴⁰ This alignment highlights the strategic relevance of the global mRNA development pipeline for strengthening future epidemic preparedness and advancing equitable access, particularly through greater LMIC engagement. By contrast, only a few candidates targeted more complex bacterial (e.g., TB) and protozoal infections (e.g., malaria). The seven CD vaccine candidates that had reached Phase III at the time of this analysis, targeted seasonal influenza (while pandemic influenza candidates were still in Phase I/II), RSV, CMV, and norovirus (Figure 3(a)). In specific, Moderna’s candidate mRNA-1345 (mRESVIA), targeting RSV, was undergoing Phase III evaluation for maternal immunization but had already received approval for adult use.^41,42 Notably, recent results for Pfizer-BioNtech’s qIRV⁴³ candidate have demonstrated statistically superior efficacy over the control vaccine, whereas Moderna’s CMV candidate mRNA-1647 did not meet its primary endpoint of preventing CMV infection in seronegative participants.⁴⁴

In contrast to the CDs pipeline, all the V&TCs targeting NCDs are therapeutic in nature and designed with varying degrees of personalization. Cancer-related V&TCs are evenly distributed across generalized, semi-personalized, and personalized strategies, while candidates targeting other NCDs predominantly have adopted a generalized approach (Figures 2(b) and S2b). Among the five cancer-related V&TCs in late-stage development (Phase II/III and Phase III) at the time of this analysis, three were fully personalized, one semi-personalized, and one generalized, the latter targeting cancers associated with human papillomavirus (HPV) infection (Supplementary Excel S1). Interestingly, one of Moderna’s personalized cancer candidates, mRNA-4157, targeting several solid tumors and in Phase III for melanoma and NSCLC, was being tested in Argentina, Brazil, Malaysia, Mexico, Peru, the Philippines, Turkey, Colombia, and South Africa. This suggests that, despite their complexity, semi-personalized and fully personalized strategies can be deployed in LMICs within highly controlled clinical trial settings. However, their feasibility in routine clinical practice in resource-limited settings remains to be demonstrated, particularly due to the advanced infrastructural and technical requirements for implementation that may be unavailable and would likely translate into high costs, further restricting access.

As illustrated in Figures 4 and 5, V&TCs were mapped using both disease-to-developer and developer-to-disease perspectives to understand clinical development pipelines by disease and developers’ portfolios. The disease-to-developer visualization (Figures 4(a) and 5(a,c)) provides a high-level view of how many developers are targeting each disease and the associated number of candidates. In contrast, the developer-to-disease visualization (Figures 4(b) and 5(b,d)) offers a more comprehensive overview of each developer and their disease targets. Developers with multiple candidates under clinical development tend to span activities across CDs and NCDs and are likely to utilize their technology as a platform, thereby offering important advantages for vaccine and therapeutic development. In fact, by maintaining consistent mRNA structure and LNP composition, developers can rapidly generate multiple candidates by simply altering the encoded antigen, while leveraging established manufacturing processes, formulation knowledge, and safety data. This modularity not only accelerates development timelines but also enhances scalability and resource efficiency, which is particularly relevant for improving access in LMICs and for addressing both CDs and NCDs.

Taken together, the disease-to-developer and the developer-to-disease projections can help manufacturers and developers by identifying key players in disease areas aligned with their commercial interests; highlighting potential stakeholders for joint ventures, co-development projects, or strategic collaborations, and supporting future market entry through licensing and technology transfer initiatives. It is important to note, however, that this analysis represents a broad landscaping exercise. Prioritization for further development and identification of specific opportunities should consider additional factors beyond the scope of this review, including scientific and technical feasibility, probability of regulatory approval, and market entry considerations that account for existing vaccines and therapeutic alternatives.

A detailed analysis of clinical trial settings revealed that, among LMICs, participation in mRNA V&TCs clinical development was dominated by UMICs, particularly China for NCDs and South Africa for CDs. Trials conducted in China were often national, non-collaborative studies, whereas other UMICs (including South Africa) and LoMICs mainly participated in multi-country trials. Participation from LICs was rare, limited to Rwanda, Liberia, and Mozambique as part of multi-country studies. China’s developer landscape was diverse, comprising domestic biotech firms, universities, hospitals, and global pharmaceutical companies. This diversity likely reflects a robust local innovation ecosystem and varied strategic priorities among stakeholders. By contrast, South Africa and Argentina were primarily engaged in clinical trials sponsored by major international companies, suggesting greater reliance on established global developers and narrower local development capacity compared with China. Overall, a narrow representation of LMICs, especially LoMICs, and LICs, was observed, highlighting the unequal inclusion of LMIC populations in clinical development activities. This imbalance may be linked to the maturity level of certain regulatory authorities; the unavailability of adequate clinical trial expertise and infrastructure; the limited presence of local R&D, largely concentrated in a few UMICs; and the limited commercial interest in LMIC countries of developers with multinational markets. Given their distinct demographic, genetic, and epidemiological characteristics, this underrepresentation underscores the ongoing challenge of generalizing randomized clinical trial results to these settings. Testing of mRNA V&TCs across a larger number of LMICs for diseases such as malaria, HIV, and TB,¹⁹ as well as cancer (in particular cervical cancer, breast cancer, and lung cancer),⁴⁵ and non-cancer NCDs (genetic disorders)⁴⁶ would require strategic attention because of their high burden in these countries.

To assess how well the V&TCs development pipeline aligned with health priorities in LMICs, this study used GBD classifications for CDs and NCDs, along with GBD data on DALYs, incidence, and prevalence for both HICs and LMICs.

Regarding CDs, difficulties in identifying appropriate matches between diseases listed in the GBD database and those in the V&TC database, aside from TB, HIV, and malaria, due to limited information on causative agents, prevented a reliable assessment of the representativeness of the pipeline for LMICs. The impact on LMICs resulting from the mapping of WHO global priority pathogens³⁸ to the diseases targeted by CD V&TCs under clinical development, should also be interpreted with caution, as the classification of countries into LMICs is based on income level, whereas the WHO evaluation followed a regional grouping. Nevertheless, although not all countries included in the GBD dataset responded to the WHO consultation, more than 70% (75.3%) of respondents were LMICs. Overall, this mapping revealed a partial overlap of 7 out of 17 (41%) priority pathogens, including: TB and HIV, which are among the five global priorities (along with extra-intestinal pathogenic Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus); RSV, recognized as a priority in all regions except the Eastern Mediterranean; Influenza, recognized as a priority in the Americas and the Western Pacific; CMV, prioritized in the Western Pacific and Europe; and Plasmodium falciparum and norovirus, prioritized in Africa and the Eastern Mediterranean, respectively.

With regard to NCDs, our findings show that although innovation in oncology is mainly driven by HICs, this does not create a major gap with the needs of LMICs. Comparative analyses of 53 types of cancer reveal a high degree of convergence in incidence profiles between these two groups of countries, with largely similar rankings and few notable differences. In particular, the cancers most often targeted in the current pipeline of mRNA vaccines and treatments correspond to those that account for the largest share of the global burden, both in HIC and LMICs, notably breast, lung, colorectal, prostate and stomach cancers.

In the broader context of other NCDs outside of cancer, both in HIC and LMICs, the number of candidates in development was too limited, and mainly concentrated on two categories of diseases, to allow solid conclusions to be drawn about the representativeness of the pipeline. It should also be noted that, for most of these diseases, antigens suitable for inclusion in an mRNA-based therapeutic vaccine or therapeutic remain to be identified, possibly explaining the limited development activities in this space.

With regard to the roll out and implementation of these technologies, many LMICs are impacted by general supply issues, including long lead time, high procurement cost of equipment and materials and limited availability of technical support, as well as by specific infrastructural challenges including cold chain logistics and limited ultra-low temperature storage,^47–50 which may continue to restrict the widespread deployment of mRNA vaccines. Advances in formulation and delivery technologies, particularly the development of thermostable vaccines, are therefore critical. Companies such as Moderna (with the CMV mRNA-1647 candidate),⁵¹ CureVac (with the rabies CV7201 candidate)⁵² and Immorna (with the Varicella Zoster JCXH-105 and the RSV JCXH-108 candidates)^53,54 are making progress by developing temperature-stable mRNA V&TCs, thereby enhancing the feasibility of broader LMIC deployment. Consequently, the selection of vaccine candidates for further development in LMICs must consider not only the disease burden but also the practical realities of logistics and infrastructure required for successful implementation and scale-up.

mRNA-based technologies represent a remarkable opportunity to accelerate the development of new vaccines and therapeutics, addressing long-standing unmet clinical needs well beyond COVID-19. They also offer an opportunity to address the equity challenges posed by NCDs, particularly cancer, where mRNA is being evaluated for therapeutic indications and for which the disease burden and inequality in care in LMICs are already high. Ensuring equitable access to this innovation requires not only aligning development efforts with global and regional public health priorities, including those specific to LMICs, but also actively involving LMICs in key phases of development, from defining target product profiles to conducting clinical trials. This study provides a comprehensive mapping of V&TCs under clinical development and their technological attributes, offering actionable insights for future development and potential partnerships tailored to local epidemiological priorities. However, it is acknowledged that this analysis is subject to limitations. In fact, although the registries used for the landscaping represent the most comprehensive sources currently available for capturing global mRNA clinical development activity, they may not be fully exhaustive, considering that some organizations may prefer not to make information publicly available, unless strictly required, or prefer using databases or websites only in local language (e.g., Chinese). In addition, this analysis provides a snapshot of a rapidly evolving mRNA vaccine landscape, in which clinical trial statuses and candidate profiles change frequently and information may not be updated on a timely and regular basis in clinical trial registries; it does not include evaluation of candidates still at pre-clinical development phase; and products at both early and later stages are susceptible to reformulation, reprioritisation, or discontinuation.⁵⁵ These shifts can affect how individual candidates are positioned or interpreted, especially as companies work to find their footing in the post-COVID-19 market and set strategic priorities. Despite these dynamics, the manuscript provides a robust framework that can support ongoing, systematic data collection and analysis as the field continues to evolve. As such, this landscaping and the framework provided, can be used by organizations based on LMICs to strategically identify, prioritize, and advance suitable mRNA technologies, fostering collaborative development initiatives and paving the way for future licensing and technology transfer opportunities.

Biography

Monica Moschioni, PhD, MPH, is a global health professional with more than 20 years of experience spanning vaccine research and development, clinical trial operations, and large-scale public health programs. She has worked across academic, pharmaceutical, and international non-governmental sectors, including the Medicines Patent Pool, Médecins Sans Frontières, GlaxoSmithKline, and Novartis Vaccines. Her expertise covers pre-clinical and clinical study design, molecular epidemiology, and the management of complex multinational projects in both high-income and low-resource settings. At the Medicines Patent Pool, she currently manages the mRNA Technology Transfer Programme and other biologicals initiatives, providing technical support, coordinating cross-functional teams, and overseeing risk, budget, and contractual processes. Previously, she led and supported multi-country Phase II–III clinical trials on multidrug-resistant tuberculosis with Médecins Sans Frontières, guiding trial implementation across Africa, Asia, and Latin America. Dr. Moschioni holds a PhD in Molecular Biology from the University of Bologna, an MPH from the London School of Hygiene & Tropical Medicine, and a degree in Chemistry and Pharmaceutical Technology from the University of Padova. She is co-author of 43 scientific publications.

Funding Statement

The work was supported by the Deutsche Gesellschaft für Internationale Zusammenarbeit.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21645515.2026.2628424