Iron deficiency and vaccine efficacy: A mini-review of immunological interplay and evidence across vaccine types

ABSTRACT

Iron deficiency (ID), the world’s most prevalent micronutrient disorder, is known to impair immune function. However, its influence on vaccine efficacy remains under-explored. This mini-review examines the interplay between iron status and immunological responses to vaccines, synthesizing evidence from human and animal studies across various vaccine types. We highlight key immune mechanisms affected by iron, such as T-cell proliferation, B-cell differentiation, and cytokine modulation, and examine how these disruptions alter vaccine responsiveness. While some studies show clear negative effects of iron deficiency, particularly in pediatric and animal models, others find minimal impact, particularly with mRNA and COVID-19 vaccines. Iron supplementation appears to improve immune outcomes in several studies, though evidence varies by pathogen, vaccine type, and severity of deficiency. These findings carry important implications for global immunization strategies, especially in iron-deficient populations. We recommend that future vaccine policy and research incorporate iron status as a critical factor in optimizing vaccine effectiveness.

Introduction

Iron is a crucial micronutrient for both innate and adaptive immunity. It supports T-cell proliferation, cytokine signaling, and antibody production, making it essential for mounting effective immune responses to infections and vaccines alike.^1,2 Iron deficiency (ID) and iron deficiency anemia (IDA) remain widespread, particularly in low- and middle-income countries, and often co-occur with high infectious disease burdens.³ As most vaccines rely on the immune system’s ability to generate durable humoral and cellular responses, the impact of ID on vaccine efficacy has significant public health implications.

Despite its biological plausibility, the relationship between ID and vaccine performance remains under-studied and inconsistently reported across vaccine types and populations. This mini-review synthesizes recent findings on how iron status may affect vaccine-induced immunity and evaluates the role of iron supplementation as a potential intervention to optimize vaccine responses.

Iron and immunity: mechanistic insights (Figure 1)

Iron plays a foundational role in the immune system. It is vital for mitochondrial respiration, DNA synthesis, and cell proliferation. T-cell and B-cell activation, central to vaccine-induced protection, are particularly sensitive to iron availability.² ID impairs dendritic cell differentiation, compromising antigen presentation and T cell priming.⁴ During activation, T and B cells upregulate surface transferrin receptor 1 (sTfR1), reflecting increased iron demand in the process.^5,6 In fact, activated T cells can increase TFRC expression up to ~ 1 million copies per cell within 24 hours, underscoring the acute iron demand during clonal expansion.⁷ Experimental blockade of TfR1 inhibits lymphocyte proliferation, highlighting the necessity of iron uptake for clonal expansion.⁸ In murine models, TfR1 deficiency leads to a complete arrest in T cell development at the triple-negative stage, while B cell maturation is partially preserved, allowing limited IgM+ cell production.⁹ Clinically, children with transferrin receptor mutations fail to express the 1µ-Cɛ transcript essential for immunoglobulin class switching, resulting in absent circulating antibodies.⁵ This effect is compounded by the fact that B-cell entry into S phase is suppressed under low iron due to impaired cyclin E1 induction, mediated via iron-dependent histone 3 lysine 9 demethylation at the cyclin promoter.^7,10 These epigenetic mechanisms highlight how iron influences not just lymphocyte proliferation, but also differentiation and memory formation.

Iron also influences macrophage polarization, cytokine secretion, and antigen presentation.¹ Macrophages have two function forms- M1 and M2. Iron promotes M1 macrophage polarization by upregulating pro-inflammatory cytokines such as TNF-α and IL-6, with iron overload amplifying this effect via the ROS/acetyl-p53 pathway.^11,12 Yet, iron’s role is context-dependent, under some conditions, it can suppress M1 activation by inhibiting STAT1 signaling.¹³ While iron accumulation in M1 macrophages enhances inflammatory cytokine output, M2 macrophages, which support tissue repair, favor iron export and attenuate cytokine secretion.¹⁴ Adding to their pro-inflammatory profile, M1 macrophages are more potent antigen-presenting cells; however, high intracellular iron may disrupt MHC expression and co-stimulatory signals, potentially impairing T cell activation.^15–17 These effects further underscore how iron availability helps shape the immunological landscape, both in promoting effector functions and in maintaining regulatory balance.

Hepcidin, a liver-produced peptide that regulates systemic iron homeostasis, is upregulated during infection and inflammation, leading to hypoferremia,a host defense strategy that limits iron availability to pathogens.^18,19 It exerts this effect by binding to Ferroportin (FPN), the sole known cellular iron exporter, inducing its internalization and degradation. Consequently, iron efflux from enterocytes, hepatocytes, and macrophages is suppressed, reducing serum iron levels. While this response limits pathogen access to iron, it inadvertently restricts iron supply to proliferating immune cells. Recent evidence indicates that such iron restriction can impair vaccine efficacy by dampening T and B cell responses and antibody production.¹⁸ Although direct studies targeting FPN in the context of vaccination are limited, its central role in regulating serum iron suggests that FPN is a key mediator of this nutrient – immunity trade-off. Notably, even transient hypoferremia during early lymphocyte expansion has been shown to impair effector function and memory recall in T cells, likely due to disrupted oxidative metabolism and IL-2 sensing.⁷ Supporting this, a study by Stoffel et al.²⁰ found that IDA and elevated serum transferrin receptor levels at the time of vaccination were strong predictors of seroconversion, highlighting a link between ID severity and vaccine responsiveness. Importantly, live and protein-based vaccines, which rely on robust T-dependent germinal center responses, may be more sensitive to iron availability than polysaccharide vaccines, which elicit weaker T-cell involvement.

Figure 1.

Vaccine types, immune pathways, and the role of iron (created via Biorender).

Evidence across vaccine types

Pediatric and animal studies

Multiple studies in piglet models and human infants show that IDA impairs vaccine responses.^18,20–24 Low serum iron concentration was associate with non-response in elderly hospitalized patients that received influenza vaccine.²⁵ A key mechanistic study using transferrin receptor mutations showed that iron uptake is essential for CD8+ T cell and germinal center B cell responses following vaccination, while iron-deficient mice exhibited impaired vaccine-specific immunity despite normal baseline immune cell numbers.¹⁸ Kenyan infants with low hemoglobin and elevated transferrin receptor (TfR) levels had lower seroconversion rates and antibody titers post-vaccination for diphtheria, pertussis, and measles.²⁴ Iron supplementation improved outcomes such as IgG avidity and seroconversion rates.²⁴ Similarly in animal models, lower vaccine responses have been reported in iron deficient piglets,¹⁸ mice and rats model,^10,23,26 which improved upon iron supplementation.¹⁸

Vaccine-specific effects

The extent to which ID impairs vaccine-induced immunity varies across vaccine platforms, likely due to differences in immunological mechanisms. Vaccines that rely heavily on T-cell activation and germinal center B-cell responses appear more sensitive to iron-dependent immune pathways such as transferrin receptor-mediated iron uptake and mTORC1 signaling.²

The influence of ID varies by vaccine platform has been summarized in Table 1.

Table 1.

The influence of iron deficiency on various vaccines.

Vaccine Type	Examples	Effect of Iron Deficiency	References
Live-attenuated vaccines	Measles, Oral polio, Varicella, Rota Virus	Reduced IgG levels, impaired seroconversion, altered memory cell development	20,27
Toxoid vaccines	Diphtheria, Tetanus, Pertussis	Strong association with Hb levels; Anaemia reduces antibody response	20,28–31
Subunit/conjugate vaccines	Pneumococcal, Hib, Hepatitis B	Variable: Reduced response in pneumococcal serotype 19; minimal/no effect in Hib and Hep B	18,20
mRNA vaccines	Pfizer-BioNTech (COVID-19)	No significant impact on neutralizing antibody levels or seroconversion in ID/IDA individuals	32–36
Viral vector vaccines	AstraZeneca (COVID-19), others	Limited data; initial studies suggest minimal impairment in IDA	37 32,34,38
Malaria vaccines	RTS,S/AS01, ME-TRAP	No effect on RTS,S vaccine; ID reduces natural immunity and enhances IFN-γ to ME-TRAP	39,40

Live-attenuated vaccines

Live-attenuated vaccines, such as measles, oral polio and rota virus, require robust humoral and cellular immunity. As explained above, these processes are iron-dependent, making such vaccines particularly sensitive to iron deficiency. Studies have shown that low iron levels compromise the adaptive immune response, particularly affecting antibody production following vaccination. For instance, Stoffel et al.²⁰ found that children experiencing IDA at the time of vaccination exhibited a significantly decreased humoral response to live vaccines. The immunological implications of ID include reduced antigen-specific antibody production and, consequently, weaker protective immunity. Additionally, iron supplementation during vaccination, as reported by Stoffel et al.²⁰ enhanced the immune response, suggesting that addressing iron levels can improve vaccine efficacy.

Furthermore, ID influences T-cell activity, which is critical for cell-mediated immunity and vital for the effectiveness of live-attenuated vaccines. Drakesmith et al.²⁷ posited that correcting ID can lead to improved vaccine responses by enhancing the proliferation and function of various immune cells, such as T-helper cells. These findings suggest that individuals deficient in iron may benefit from targeted interventions prior to vaccination to optimize their immune responses to these vaccines.

Although no studies have directly assessed the impact of ID on OPV or rotavirus vaccine responses, both have shown reduced immunogenicity in the context of zinc deficiency,⁴¹ likely due to their reliance on membrane integrity and mucosal immunity. Given iron’s central role in T and B cell function, it is biologically plausible that ID could similarly impair immune responses to these vaccines.

Toxoid vaccines

Toxoid vaccines, such as diphtheria and tetanus, stimulate T-helper-dependent antibody responses, which rely on effective activation of dendritic cells, T-helper cells, and B cells, all of which are iron-dependent. As explained above, iron supports key processes such as mitochondrial respiration, DNA synthesis, and epigenetic regulation required for lymphocyte proliferation and function. Early studies reported mixed findings: while iron-deficient children failed to mount responses to diphtheria vaccine,³¹ responses to tetanus, typhoid, and influenza vaccines were not consistently affected.^29,30 However, more recent controlled studies in Kenyan infants show that IDA at the time of immunization is associated with reduced humoral responses to diphtheria vaccine.²⁰ Mechanistically, ID impairs T-helper cell proliferation and antigen presentation, and induces oxidative stress, compromising macrophage and T cell function, both of which are essential for toxoid vaccine efficacy.^27,28 Animal studies further support this: iron-deficient mice and small ruminants vaccinated under low-iron conditions showed significantly lower antibody titers than iron-replete counterparts.²⁸ These findings underscore the need to address iron status, particularly in vulnerable populations such as young children and pregnant women, to optimize immune responses to toxoid-based vaccines.⁴²

Subunit and conjugate vaccines

Subunit and conjugate vaccines,such as the pneumococcal conjugate vaccine (PCV), Haemophilus influenzae type B (Hib), and hepatitis B, depend on T-helper cell-mediated B cell activation to elicit high-affinity antibody responses and immunological memory.⁷ As discussed above, these T-dependent responses are highly sensitive to iron availability, which supports mitochondrial metabolism, cell proliferation, and epigenetic remodeling in lymphocytes. Although conjugate vaccines do not mimic natural infection like live-attenuated vaccines, they rely on similar immunological pathways, particularly germinal center formation and class switching, both of which are impaired under iron-deficient conditions.

In individuals with ID, particularly those with mutations in TMPRSS6 leading to iron-refractory IDA and elevated hepcidin, reduced antibody titers have been observed against Hib and Streptococcus pneumoniae serotype 1 compared to healthy controls.¹⁸ These findings highlight how impaired iron homeostasis, not just low dietary intake, can compromise vaccine-induced immunity.

Conjugate vaccines incorporate polysaccharide antigens linked to protein carriers to activate immature immune systems via T-helper pathways. Adequate iron is essential for B cell maturation and antibody class switching, and its deficiency likely impairs these steps, thereby reducing vaccine effectiveness.^18,20 Supporting this, a study in Kenyan infants showed reduced antibody responses specifically to pneumococcal serotype 19, which correlated with elevated transferrin receptor (TfR) levels, a marker of cellular iron demand.²⁰ However, responses to other PCV serotypes and hepatitis B did not show consistent differences, suggesting that iron dependency may vary by antigen or vaccine formulation. These data underscore the nuanced but critical role of iron status in shaping the efficacy of conjugate vaccines, particularly in populations vulnerable to iron deficiency.

mRNA vaccines

mRNA vaccines, such as BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), have been instrumental in combating the COVID-19 pandemic. These platforms elicit strong innate and adaptive immune responses, largely through the activation of dendritic cells, T follicular helper cells, and germinal center B cells. As discussed above, these processes depend on iron for mitochondrial metabolism, DNA synthesis, and cytokine signaling, raising concerns that IDA may impair vaccine efficacy. While IDA has been broadly associated with reduced vaccine responsiveness, evidence specific to mRNA vaccines remains mixed.

In a longitudinal cohort study, Faizo et al.³² found that ID did not significantly affect neutralizing antibody production, seroconversion rates, or overall protection following mRNA COVID-19 vaccination. This may reflect the potent immunostimulatory nature of mRNA platforms, which can partially bypass iron-sensitive checkpoints in adaptive immunity. In contrast, a large real-world study by Tene et al.³⁶ and Gujjarlapudi et al.³⁴ reported that individuals with ID had lower seroconversion rates and antibody titers in response to BNT162b2, suggesting that even mRNA vaccine efficacy may be reduced under iron-limited conditions.

In recognition of these concerns, the European Hematology Association issued guidance in 2021 recommending the correction of ID prior to COVID-19 vaccination in individuals with hematologic disorders.⁷ Supporting this, case reports have noted adverse immune responses such as autoimmune hemolytic anemia post-vaccination, raising the possibility that preexisting IDA may exacerbate immune dysregulation.^33,35 Although a direct causal link remains unproven, these findings highlight the importance of monitoring hemoglobin and iron status, particularly in vulnerable populations receiving vaccines that depend on robust adaptive immunity.

Viral vector vaccines

Viral vector vaccines, such as ChAdOx1 nCoV-19, rely on both innate and adaptive immune activation to elicit protective responses, including type I interferon signaling and robust T-helper and B cell engagement. As outlined above, these immune pathways are sensitive to iron availability, which supports T cell proliferation, cytokine production, and antibody formation. Although data remain limited, early findings suggest that ID may have variable effects on vector-based vaccines. For instance, Faizo et al.³² observed no significant impairment in immune responses to COVID-19 viral vector vaccines in iron-deficient individuals, though mechanistic studies are sparse.

In contrast, works by Gujjarlapudi et al.³⁴ and Zhong et al.³⁸ demonstrated that type I interferon signaling, essential for effective humoral immunity, is compromised under iron-deficient conditions, potentially diminishing the immunogenicity of viral vector platforms. Similarly, Tansawet et al.³⁷ suggest that reduced iron availability may impair the T-helper cell responses critical to the efficacy of ChAdOx1 nCoV-19. While observational studies have begun to explore vaccine performance across iron status, the direct influence of ID on viral vector vaccine efficacy and safety remains poorly understood. Further research is needed to clarify whether correcting ID could enhance immune protection in this context.

Malaria vaccines

The RTS,S/AS01 malaria vaccine has been shown to elicit comparable antibody responses in both iron-deficient and iron-replete children.³⁹ However, natural immunity to malaria was significantly diminished in iron-deficient individuals, suggesting that while the vaccine may partially bypass iron-sensitive immune pathways, effective infection control still depends on intact iron-supported mechanisms. As previously discussed, iron is essential for T and B cell activation, cytokine production, and memory formation, processes critical for controlling parasitic infections such as Plasmodium falciparum. For example, reduced immunogenicity has been observed in response to Leishmania chagasi⁴⁰ and malaria infection and vaccines,^39,43 indicating that ID may broadly compromise the effectiveness of vaccines targeting parasitic infections. These findings reinforce the need to assess and correct iron status, especially in endemic regions where ID and parasitic disease burden frequently coexist.

Role of iron supplementation

The potential for iron supplementation to improve vaccine efficacy has become a growing area of interest, especially in populations where ID and IDA are prevalent. Iron is essential for lymphocyte activation and proliferation, supporting processes such as TFRC-mediated iron uptake, mitochondrial metabolism, and antibody class switching, as discussed above. These mechanisms provide the biological basis for the growing body of evidence showing that iron supplementation can enhance vaccine-induced immunity in iron-deficient populations.

Several studies underscore the immunological benefits of correcting iron deficiency. In a randomized controlled trial, Stoffel et al.²⁰ demonstrated that Kenyan infants receiving iron-containing micronutrient powder showed significantly improved antibody responses to measles and other routine vaccines compared to un-supplemented peers. Frost et al.¹⁸ further supported this, reporting that anemia was associated with weaker humoral responses in Kenyan infants, and that iron supplementation led to enhanced vaccine-induced antibody levels. Similarly, Tene et al.³⁶ found that individuals with ID exhibited poorer immune responses to diphtheria, tetanus, and pertussis vaccines, reinforcing the importance of adequate iron levels for effective adaptive immunity.

Additional evidence from maternal and pediatric populations further strengthens this association. Zhang et al.⁴⁴ reported that iron supplementation during pregnancy improved infant antibody responses to several childhood vaccines, suggesting that maternal iron status can influence neonatal vaccine efficacy. In a related study, Zhang et al.⁴⁵ found that while iron had limited impact on antibody levels following SARS-CoV-2 vaccination, it enhanced responses to other childhood vaccines such as DTP and pneumococcal vaccines in pregnant women. Moreover, Saha et al.⁴⁶ showed that iron supplementation improved T-cell counts and function in children with IDA, providing direct evidence that cell-mediated immunity can be restored with improved iron status, even when immunoglobulin levels remain unchanged.

Together, these findings support the conclusion that iron supplementation can improve both humoral and cellular immune responses to vaccination, particularly in iron-deficient populations. However, the magnitude of benefit may depend on factors such as the vaccine type, timing of supplementation, and host immune status, highlighting the need for standardized, context-specific strategies in future intervention studies.

Furthermore, the form of supplementation (oral vs. intravenous), timing relative to vaccination, and baseline iron biomarkers (e.g., serum ferritin, hepcidin, TfR) appear to be critical variables influencing outcomes. These factors must be standardized in future interventional studies to guide clinical recommendations effectively.

Knowledge gaps and future directions

Despite the growing body of evidence linking iron status to vaccine efficacy, significant knowledge gaps remain that limit clinical translation.

Lack of stratification by severity of iron deficiency

Most studies treat ID as a binary condition. However, evidence from the Kenyan birth cohort suggests that the degree of iron deficiency, as measured by hemoglobin levels and transferrin receptor expression, correlates with the strength of the vaccine response. Future studies should stratify subjects by mild, moderate, and severe IDA, using standardized WHO thresholds.

Uncertainty across vaccine platforms

While ID clearly impairs responses to toxoid, protein subunit, and live-attenuated vaccines, its effect on mRNA and viral vector platforms is inconsistent. For instance, studies on the Pfizer-BioNTech COVID-19 vaccine indicate no significant reduction in neutralizing antibodies among iron-deficient individuals, even though other research highlights iron’s role in T cell activation. This suggests that not all vaccines are equally iron-dependent, and platform-specific investigations are necessary.

Unclear durability of immune memory

Animal studies have shown that ID during primary immunization can alter the development of memory T and B cells, resulting in a weaker secondary response, even after iron levels are restored. Also most studies have been limited by measuring short term response and there is a notable gap in research examining the durability of immune memory in iron-deficient individuals. There is a lack of longitudinal human studies assessing how iron status at the time of vaccination affects the persistence of antigen-specific memory B cells and T cells, which are critical for influenceing long-term immunity, including booster responsiveness. This is especially important for vaccines that rely on long-term cellular immunity, such as those for hepatitis B, COVID-19, or HPV. Addressing this gap would require prospective studies with extended follow-up periods and integrated immunophenotyping to evaluate both humoral and cellular memory responses over time. Understanding the extent to which early-life or prenatal iron deficiency may impair durable immunity is also crucial for informing maternal and infant vaccination strategies.

Timing and dose of supplementation

Though many of the populations are prioritized for iron supplementation by the World Health Organization (WHO), including pregnant women, infants, and children with severe acute malnutrition (SAM),⁴⁷ iron supplementation and vaccination efforts are not always synchronized in practice. For example, the Expanded Programme on Immunization (EPI) typically administers primary series vaccines in early infancy, beginning before six months of age, prior to the routine start of iron supplementation. Similarly, pregnant women may receive tetanus toxoid or COVID-19 vaccines during antenatal visits, but without consistent assessment or correction of iron status. This disconnect presents an opportunity for greater integration of services.

Aligning iron supplementation with immunization schedules may enhance vaccine efficacy, particularly for live or protein-based vaccines that rely on robust T- and B-cell responses. Such alignment could involve point-of-care ferritin screening, iron-inclusive maternal or child health platforms, or synchronized community delivery strategies. In resource-limited settings with high burdens of both ID and vaccine-preventable disease, this integrative approach could yield significant public health gains

Also, there is little consensus on whether iron should be administered before, during, or after vaccination for maximal benefit. Additionally, optimal dosing strategies, especially in pediatric and malnourished populations, remain unclear. While oral iron is safe and inexpensive, it may have limited bioavailability in the context of inflammation-driven hepcidin elevation, common in infection-prone settings.

Lack of randomized controlled trials (RCTs)

Although several observational and animal studies suggest a positive role for iron supplementation, few RCTs have directly evaluated its effect on vaccine efficacy. High-quality, multicenter RCTs are needed to:

• Determine causal relationships

• Test different iron formulations

• Assess cost-effectiveness of integrating iron screening into vaccination programs

Furthermore most existing studies have focused on infants and pregnant women in LMICs, leaving out older adults, adolescents, and individuals with chronic diseases or inflammatory conditions. Future studies should prioritize underrepresented populations such as the elderly, individuals with chronic illnesses, and pregnant women, where data on the interaction between iron status and vaccine response remain sparse. These groups often exhibit altered immune profiles or higher risk of iron deficiency, yet remain under-investigated in clinical trials assessing vaccine immunogenicity and iron intervention. Addressing these gaps is critical for ensuring equitable and effective vaccine protection across the life course.

All the recommendations’ have been summarized in Table 2.

Table 2.

Practical takeaways for clinicians, researchers, and public health professionals.

1. Assess iron status before routine immunization, especially in high-risk groups

2. Prioritize supplementation for those receiving live-attenuated or toxoid vaccines

3. Time iron supplementation appropriately to improve vaccine response

4. Use oral iron cautiously during infection/inflammation due to hepcidin effects

5. Customize vaccine strategies based on nutritional and immune status

Ethical and public health considerations

In resource-limited settings, where both IDA and vaccine-preventable diseases are common, iron supplementation programs could enhance herd immunity and reduce disease burden. However, iron also enhances pathogen growth, and indiscriminate supplementation could have unintended consequences, especially during ongoing infections. A nuanced understanding of nutritional immunity is needed to balance risks and benefits.

The double-edged role of iron in immunity and infection

Iron supplementation during infection or inflammation presents complex challenges due to its interaction with hepcidin, an iron-regulating hormone elevated during inflammatory states. Increased hepcidin leads to hypoferremia and reduces iron bioavailability in immune-critical tissues, potentially undermining the benefits of supplementation. Several studies caution against indiscriminate iron administration in such contexts. While iron is essential for immune function, its excess can impair pathogen clearance and promote microbial proliferation, as noted by Herdes et al.⁴⁸ Löw et al.⁴⁹ and Agoro & Mura¹ Clinical data from Schimmer et al.⁵⁰ and McMillen et al.⁵¹ further highlight the variable outcomes of supplementation, particularly among individuals with active infections or vulnerable populations like infants. Fowkes et al.⁵² also observed increased mortality risk when iron was given in malaria-endemic regions without individualized assessment. These findings underscore the importance of careful iron status evaluation and context-specific decision-making. While correcting iron deficiency remains critical, iron supplementation in inflammatory settings must be approached with caution to avoid unintended harm.

Conclusion

ID can compromise immune responses to several vaccines, particularly those relying on T-cell and B-cell activation. While some vaccine platforms, such as mRNA, appear resilient, others, like toxoid and live-attenuated vaccines, like measles and DPT, show reduced efficacy in iron-deficient individuals. Iron supplementation has shown promise in restoring immune function, though its effectiveness varies by context and requires further study. Given the high global burden of both ID and vaccine-preventable diseases, integrating iron assessment into immunization strategies may enhance vaccine effectiveness and public health outcomes. However, more evidence is needed to determine the optimal use of iron interventions in immunization programs. At present, iron supplementation should be seen as a promising adjunct rather than a proven solution for improving vaccine efficacy.

Biography

Mariam Shadan is a medical educator, pathologist, and interdisciplinary researcher with expertise spanning medical education, pathology, and health equity. Dr. Shadan’s research portfolio includes work in haematology and hematopathology, with published studies on artificial platelets, blood substitutes, and diagnostic challenges in hematologic malignancies. Her contributions reflect a strong interest in translational science and diagnostic precision.

In parallel, she leads a pioneering line of inquiry into non-digital gamification in health professions education. As principal investigator on several randomized controlled trials, she evaluates the impact of low-cost, analog board and card games on learning outcomes across disciplines such as physiology, pharmacology, and clinical reasoning.

Her work emphasizes scalable, stress-reducing learning models tailored to diverse and resource-limited settings. She has published in numerous international peer reviewed journals, and collaborates internationally to advance inclusive, evidence-based pedagogy. Dr. Shadan is driven by the belief that better learning leads to better healthcare, and ultimately, a more equitable world.

Funding Statement

The author(s) reported there is no funding associated with the work featured in this article.

Disclosure statement

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

Data availability statement

Data sharing is not applicable to this article as no new data was created or analyzed in this study.

Ethics approval

As this is a reviewed article comprising of already published articles in the area, ethical approval was not required for the same.

ICMJE authorship criteria

MS- initial conception. All authors contributed equally to data analysis, manuscript writing and revision of final manuscript.