Introduction

Vaccination is one of the most effective public health interventions for preventing infectious diseases and reducing child mortality.1 However, in low- and middle-income countries (LMICs) where malnutrition is prevalent, the effectiveness of vaccines is often compromised. Malnutrition weakens the immune system, leading to suboptimal immune responses to vaccines, which leaves malnourished children more vulnerable to vaccine-preventable diseases such as measles, polio, and rotavirus.2–4 Disparities in vaccine efficacy are further pronounced in rural areas compared to urban settings, underscoring the need for targeted interventions in underprivileged regions.5

Micronutrient deficiencies, particularly in vitamin A, zinc, and iron, are known to impair both cellular and humoral immunity, crucial for an effective response to vaccines. Vitamin A deficiency weakens mucosal barriers and reduces the production of antibodies, which are critical for preventing infections. Similarly, zinc deficiency has been shown to impair immune cell function, resulting in weakened mucosal immunity and lower seroconversion rates for oral vaccines like the oral polio vaccine (OPV). The effects of malnutrition on vaccine efficacy are not limited to OPV and rotavirus but extend to vaccines such as Hepatitis B and DTP, highlighting the systemic impact of malnutrition on immunity.6,7 Iron deficiency affects the proliferation and function of immune cells, reducing the body’s ability to mount an adequate vaccine response.8

Despite significant global immunization efforts, malnourished children in LMICs continue to experience lower rates of seroconversion following vaccination compared to their well-nourished counterparts. For example, research indicates that children suffering from protein-energy malnutrition show 30–40% lower seroconversion rates after receiving the OPV. Vaccine efficacy varies significantly between LMICs and high-income countries, with children in LMICs often experiencing reduced immune responses due to malnutrition and environmental factors, emphasizing the need for tailored interventions9 This challenge highlights the urgent need for comprehensive approaches that integrate nutritional interventions with immunization programs to improve vaccine outcomes in malnourished populations.

While existing literature has explored the effects of individual vaccines on malnourished populations, there remains a significant gap in understanding the cumulative impact of chronic malnutrition on immune system function across multiple vaccines.10 In particular, the effects of malnutrition on oral vaccines such as rotavirus and OPV are more pronounced, given that these vaccines rely heavily on mucosal immunity, which is often compromised in malnourished children. Injectable vaccines, such as measles, are also affected but to a lesser extent, with malnourished children showing up to 35% failure to develop protective immunity.

This article proposes a new conceptual framework that integrates nutritional status, immune function, and environmental context to explain why malnourished children exhibit reduced vaccine efficacy. It also outlines targeted interventions, such as vitamin A supplementation, zinc fortification, and flexible immunization schedules, which could improve vaccine responses in malnourished populations. By addressing both the nutritional deficiencies and the environmental factors that exacerbate immune suppression, this framework offers a comprehensive approach to tackling one of the most pressing public health challenges in LMICs.

Existing literature has extensively documented the relationship between malnutrition and immune suppression.11–13 For instance, deficiencies in key micronutrients like vitamin A, zinc, and iron compromise both cellular and humoral immunity, which are critical for an effective vaccine response.10,14 Maternal nutrition significantly impacts neonatal immunity, with deficiencies in key micronutrients during pregnancy leading to weaker immune responses in newborns and reduced vaccine efficacy15 However, current immunization programs often fail to integrate nutrition as a fundamental factor influencing vaccine efficacy. Immunization programs in LMICs often face resource constraints and policy gaps that limit the integration of nutritional interventions, despite evidence supporting their efficacy in improving vaccine responses.16 As a result, malnourished children frequently exhibit lower seroconversion rates and reduced protective immunity compared to their well-nourished counterparts.17

While several studies have explored the impact of malnutrition on specific vaccines, there is a gap in the literature when it comes to providing a comprehensive framework that integrates nutritional status, immune function, and environmental conditions as a collective explanation for poor vaccine efficacy in malnourished populations. This article addresses that gap by proposing a new conceptual framework that highlights the interplay of these factors and offers targeted interventions to improve vaccination outcomes in malnourished populations.

This framework differs from existing studies by providing a holistic approach to understanding how malnutrition affects vaccine efficacy.

It accounts not only for nutritional deficiencies but also the environmental contexts, such as poor sanitation and high exposure to infections, that exacerbate malnutrition and reduce immune responses. By identifying the synergistic effects of these factors, this framework offers a more comprehensive basis for designing interventions that go beyond traditional vaccination programs.

Current Understanding of Vaccine Efficacy and Malnutrition Impact of Malnutrition on Immune Function

Malnutrition, particularly micronutrient deficiencies and protein-energy malnutrition, significantly impairs immune function. Malnourished children exhibit reduced levels of critical immune cells, including T cells and B cells, which are essential for mounting an effective response to vaccines.11,18,19 In addition, malnutrition diminishes the production of antibodies, which are crucial for long-term immunity.20 This impaired immune function leads to reduced vaccine efficacy, leaving malnourished children vulnerable to vaccine-preventable diseases such as measles, polio, and rotavirus systemic immune response challenges due to impaired cellular and humoral immunity.21,22

As discussed in the introduction, micronutrient deficiencies, particularly vitamin A, zinc, and iron, significantly impair immune responses in malnourished children, affecting both mucosal and systemic immunity.

Vaccine Efficacy in Malnourished Children

Studies show that malnourished children have lower seroconversion rates and reduced immune responses to vaccines compared to their well-nourished peers. For instance, a study on the oral polio vaccine (OPV) demonstrated that malnourished children had lower antibody titers after vaccination, making them more susceptible to polio outbreaks. Similarly, the immune response to measles and rotavirus vaccines is often diminished in malnourished children, leading to incomplete protection against these diseases.

This reduced efficacy is not limited to oral vaccines. In many cases, malnourished children also experience weaker responses to injectable vaccines, suggesting that the impact of malnutrition on the immune system is systemic, affecting both cellular and humoral immunity.

Gaps in the Literature

While it is well-documented that malnutrition impairs immune responses, there is a gap in understanding how different forms of malnutrition (acute vs chronic) and varying levels of nutrient deficiencies interact with environmental and immunological factors to affect vaccine efficacy. Moreover, current immunization campaigns rarely account for the nutritional status of children, leading to suboptimal vaccination outcomes in malnourished populations. Overlapping interventions, such as nutritional supplementation alongside vaccination schedules, must consider potential interactions to optimize both vaccine efficacy and nutritional outcomes.23

Methodology

This study utilized a literature review approach, analyzing existing cross-sectional surveys, immunization data, and peer-reviewed research to examine the relationship between malnutrition and vaccine efficacy in children. The focus was on children aged six months to five years in low- and middle-income countries (LMICs), particularly those receiving vaccines for diseases such as polio, measles, and rotavirus. By examining three key domains—nutritional status, immune function, and environmental context—the study aimed to understand how these factors collectively impact vaccine efficacy in malnourished children.

Study Selection Criteria

To ensure the reliability and relevance of the findings, the following inclusion criteria were applied when selecting studies:

Geographical Focus: Only studies conducted in LMICs were included, as these regions have the highest burden of malnutrition and are often the focus of global immunization efforts. Sample Size: Studies with a sample size of at least 100 participants were included to ensure the statistical power of the results and to improve the generalizability of the findings. Quantitative Data: The review focused on studies that reported quantitative data on seroconversion rates, antibody titers, or immune responses following vaccination. Studies that included specific metrics on vaccine efficacy in malnourished populations were prioritized. Vaccine Types: Both oral vaccines (eg, OPV, rotavirus) and injectable vaccines (eg, measles, diphtheria, tetanus) were included to compare the effects of malnutrition on different immune pathways (mucosal vs systemic immunity). Nutritional Status: Studies were included if they assessed vaccine responses in children with diagnosed protein-energy malnutrition or micronutrient deficiencies (eg, vitamin A, zinc, iron). Publication Date: Studies published between 2000 and 2024 were included to ensure that the findings were relevant to contemporary public health challenges and immunization strategies.Exclusion Criteria

Studies were excluded from the review if they met any of the following criteria:

Studies conducted in high-income countries, as their findings may not be applicable to the LMIC context. Studies with a sample size below 100 participants, which may lack sufficient statistical power. Studies that only provided qualitative data or anecdotal evidence without quantitative measures of vaccine efficacy. Studies that focused exclusively on adults, as the immune responses and nutritional needs of children differ significantly.Data Analysis

After identifying relevant studies, data were extracted and analyzed based on the reported seroconversion rates, antibody titers, and other immunological markers. The review compared the vaccine responses of malnourished children to those of well-nourished children, with a particular focus on differences between oral vaccines (which depend on mucosal immunity) and injectable vaccines (which rely on systemic immunity). The analysis also considered how different forms of malnutrition (acute vs chronic) impacted vaccine efficacy.

Rationale for Study Selection

The studies chosen for this review were selected because they provided comprehensive data on both nutritional status and immune function, offering valuable insight into the specific challenges malnourished children face when vaccinated. Studies that assessed both oral and injectable vaccines were prioritized to capture the broader scope of vaccine efficacy across different vaccine types. Additionally, research focusing on micronutrient supplementation (eg, vitamin A, zinc, and iron) was included to identify evidence-based interventions that could enhance immune responses in malnourished populations.

Results

The findings from the literature review confirm that malnourished children consistently exhibit significantly lower seroconversion rates compared to their well-nourished counterparts across multiple vaccines. This review highlighted the impact of malnutrition on both oral and injectable vaccines, with a particular focus on the oral polio vaccine (OPV), measles, and rotavirus vaccines.

Polio Vaccine (OPV)

Studies demonstrated that children with protein-energy malnutrition and micronutrient deficiencies, particularly deficiencies in zinc and vitamin A, experienced seroconversion rates approximately 30–40% lower than well-nourished children.24 As shown in Figure 1, children with protein-energy malnutrition experienced reduced OPV seroconversion rates, significantly increasing their risk for polio outbreaks.

Figure 1 Seroconversion Rates for OPV in Malnourished vs Well-Nourished Children.

Measles Vaccine

In regions with high prevalence of chronic malnutrition, up to 35% of vaccinated children failed to develop adequate protective immunity, as indicated by low measles-specific antibody levels.25Figure 2 demonstrates the correlation between chronic malnutrition and reduced measles immunity, showing a 35% failure to achieve protective immunity. These findings suggest that while vaccination campaigns have successfully expanded coverage, they may not be fully protective for malnourished populations unless nutritional interventions are included.

Figure 2 Correlation between malnutrition and measles vaccine efficacy.

Rotavirus Vaccine

Rotavirus vaccines also displayed significantly reduced efficacy in malnourished children, particularly those suffering from acute malnutrition. Seroconversion rates in malnourished children were as much as 50% lower compared to their well-nourished counterparts.26Figure 3 illustrates the impaired immune response in malnourished children receiving the rotavirus vaccine, highlighting the heightened risk of severe rotavirus infections in malnourished populations.

Figure 3 Seroconversion Rates for Rotavirus Vaccine.

Impact of Environmental Factors

The results also revealed that poor environmental conditions, such as lack of access to clean water and sanitation, exacerbate the negative effects of malnutrition on vaccine efficacy. In regions with high exposure to enteric infections, malnourished children had significantly lower antibody titers post-vaccination, as shown in Figure 4. These findings support the conclusion that environmental factors, alongside malnutrition, contribute to the reduced efficacy of vaccines, particularly those administered orally like OPV and rotavirus vaccines.11,27,28

Figure 4 Impact of Poor Environmental Conditions on Vaccine Efficacy.

Synergistic Effects of Malnutrition and Immune Suppression

The review identified a clear feedback loop wherein malnutrition leads to immune suppression, which increases susceptibility to infections, further exacerbating malnutrition. This cycle, illustrated in Figure 5, underpins the consistently lower vaccine efficacy observed in malnourished children. The interaction between malnutrition, immune suppression, and poor environmental conditions creates a complex barrier to achieving effective immunization in LMICs.

Figure 5 Feedback Loop of Malnutrition, Immune Suppression; and Infection.

Intervention Success

Nutritional interventions, particularly supplementation with micronutrients such as vitamin A and zinc, were found to significantly improve immune responses and seroconversion rates in malnourished children. For example, children who received vitamin A supplementation prior to measles vaccination demonstrated seroconversion rates that were 25–30% higher than those who did not receive supplementation.29Figure 6 provides a comparative view of the improvement in seroconversion rates with and without supplementation, underscoring the importance of integrating nutrition into immunization programs.

Figure 6 Seroconversion Rates with and without Nutritional Supplementation.

Similarly, implementing flexible immunization schedules—such as delaying vaccinations until nutritional status improves or administering booster doses to malnourished children—has been shown to enhance vaccine efficacy in severely malnourished populations.

The New Conceptual Framework Overview

This framework posits that vaccine efficacy in malnourished children is determined by the interaction of three key domains: nutritional status, immune function, and environmental context. These domains collectively influence how a child’s body responds to vaccines, particularly in settings where malnutrition and infectious diseases are prevalent.30–32

In Haut-Lomami and Tanganyika, regions with high rates of environmental enteropathy and chronic malnutrition, the proposed framework suggests prioritizing nutritional supplementation with vaccines. The framework also advocates for improving environmental sanitation to reduce enteric infections, thus enhancing vaccine efficacy.

Key Components of the Framework Nutritional Status: Malnutrition weakens the body’s ability to mount an effective immune response to vaccines. Different forms of malnutrition (eg, protein-energy malnutrition, micronutrient deficiencies) have distinct effects on the immune system. Chronic malnutrition, for instance, is associated with stunted growth and a persistently weakened immune system, whereas acute malnutrition may have more immediate but reversible impacts on immune function.24,33 Key micronutrients like vitamin A, zinc, and iron are critical for immune responses, and their deficiencies contribute to poor vaccine efficacy. Immune Function: Malnourished children exhibit reduced T-cell proliferation, impaired B-cell function, and a diminished production of antibodies following vaccination. This impaired immune response is particularly pronounced for vaccines that rely on mucosal immunity, such as oral polio and rotavirus vaccines. The suppression of immune functions in malnourished children makes them more susceptible to infections and reduces the effectiveness of vaccines. Environmental Context: The living environment of a child plays a crucial role in shaping their health and immune responses, particularly in low- and middle-income countries (LMICs). Environmental factors, such as poor sanitation, high exposure to infectious agents, and limited access to clean water, contribute significantly to the cycle of malnutrition and reduced vaccine efficacy. These challenges disproportionately affect children in resource-constrained settings, further compounding the burden of vaccine-preventable diseases.341) Poor Sanitation and Hygiene Poor sanitation fosters an environment conducive to the transmission of enteric pathogens, leading to frequent gastrointestinal infections such as diarrhea. These infections directly impact the intestinal barrier, a critical component of mucosal immunity. Research by Marie et al highlights that compromised intestinal integrity, a condition referred to as environmental enteric dysfunction (EED), significantly reduces the efficacy of orally administered vaccines like oral polio vaccine (OPV) and rotavirus vaccines. EED not only limits the absorption of nutrients but also impairs immune signaling pathways necessary for an effective vaccine response.2) High Burden of Infections Children living in overcrowded or unsanitary conditions face a continuous exposure to pathogens, including bacteria, viruses, and parasites. Repeated infections place a chronic inflammatory burden on the immune system, impairing its ability to respond to vaccinations effectively. Frequent infections, such as enteric or parasitic infections, deplete the already limited nutritional reserves of malnourished children, further reducing their ability to mount an adequate immune response. This cyclical interaction perpetuates the vicious cycle of malnutrition, infection, and reduced vaccine efficacy.3) Impact on Oral Vaccine Efficacy

“Oral vaccines, such as OPV and rotavirus, are particularly affected by these environmental conditions. Unlike injectable vaccines, oral vaccines rely heavily on the integrity of the gut mucosa to elicit an immune response. In the presence of EED, the gut’s ability to respond to these vaccines is significantly impaired, leading to lower seroconversion rates and suboptimal protective immunity”. “Emerging research suggests that gut microbiota play a crucial role in shaping immune responses to oral vaccines, with malnourished children often exhibiting dysbiosis that impairs mucosal immunity”.35,36

4) Broader Implications

“The implications of poor sanitation extend beyond oral vaccines. Chronic infections and inflammation caused by poor environmental conditions weaken systemic immunity as well, affecting the efficacy of injectable vaccines like measles and diphtheria”.

5) Integrated Interventions Addressing these challenges requires comprehensive interventions. For example: Implementation of Water, Sanitation, and Hygiene (WASH) programs can reduce the transmission of enteric infections. Promoting hygiene practices, such as handwashing and safe food preparation, can minimize pathogen exposure. Deworming programs targeting parasitic infections can alleviate nutritional depletion and immune suppression caused by helminths.

“Marie et al emphasized that integrating WASH initiatives with vaccination campaigns significantly enhances vaccine outcomes. In regions with improved sanitation, children show better growth metrics and higher seroconversion rates for oral vaccines.28 The interaction between nutritional status, immune function, and environmental factors is illustrated in Figure 7”.

Figure 7 Simplified version of the conceptual framework showing the interaction between nutritional status, immune function, and environmental context in influencing vaccine efficacy in malnourished children.

Synergistic Effects

The interaction of these three domains creates a feedback loop that undermines vaccine efficacy in malnourished children. Malnutrition leads to immune suppression, which increases susceptibility to infections, and these infections, in turn, exacerbate malnutrition. In environments with poor sanitation, the burden of enteric diseases like diarrhea further weakens the immune system, diminishing the effectiveness of vaccines. This conceptual framework underscores the importance of addressing not only malnutrition but also the broader environmental factors that contribute to poor vaccine outcomes in LMICs.

Proposed Interventions to Enhance Vaccine Efficacy

Given the significant impact of malnutrition on vaccine efficacy, particularly for oral vaccines, targeted interventions are necessary to improve immunization outcomes in malnourished populations. The proposed interventions focus on nutritional supplementation, flexible immunization schedules, and environmental health improvements. These interventions have been successfully implemented in low-resource settings and provide valuable lessons for addressing the challenges of vaccine efficacy in malnourished children.

Nutritional Supplementation Strategies

Nutritional supplementation, particularly with vitamin A, zinc, and iron, has been shown to significantly improve immune responses and seroconversion rates in malnourished children. Vitamin A supplementation is especially crucial, as it plays a key role in maintaining mucosal surfaces and boosting immune function. Studies conducted in Bangladesh and Ethiopia have demonstrated the effectiveness of integrated supplementation and vaccination programs.

For instance, in Bangladesh, a campaign that integrated vitamin A supplementation with measles vaccination resulted in a 25% improvement in seroconversion rates among malnourished children.36 The success of this program highlights the potential for similar interventions to be replicated in other LMICs where vitamin A deficiency is prevalent. Additionally, the combination of zinc supplementation with vaccines like OPV has been shown to enhance mucosal immunity, leading to improved vaccine efficacy.37

In Ethiopia, where malnutrition rates are high, the introduction of routine nutritional assessments during vaccination campaigns has allowed healthcare workers to identify children at risk of malnutrition and provide targeted nutritional support. This approach has improved the overall vaccine coverage and reduced the incidence of vaccine-preventable diseases, particularly in rural and hard-to-reach areas.38,39

Timing and Dosing Adjustments

Flexible immunization schedules can further enhance vaccine efficacy in severely malnourished populations. Delaying vaccinations until a child’s nutritional status improves, or administering booster doses to malnourished children, has been shown to increase the effectiveness of vaccines. In settings where acute malnutrition is prevalent, providing booster doses of vaccines such as measles and OPV has been a successful strategy for ensuring adequate immune protection.40

For example, in a study conducted in Kenya, children suffering from acute malnutrition who received booster doses of the measles vaccine showed a marked improvement in antibody titers, reaching levels comparable to those of well-nourished children.7,41 This approach underscores the importance of adapting immunization schedules to the nutritional needs of the population, ensuring that malnourished children receive the full benefits of vaccination.

Environmental Health Interventions

Improving the environmental conditions in which malnourished children live is another critical intervention. Poor sanitation and lack of access to clean water exacerbate the effects of malnutrition and reduce the efficacy of vaccines, particularly oral vaccines like rotavirus and OPV. Addressing these environmental factors through water, sanitation, and hygiene (WASH) programs can have a profound impact on vaccine outcomes.

In Nepal, a program that combined rotavirus vaccination with efforts to improve access to clean water and promote hygiene practices resulted in a significant reduction in the incidence of rotavirus infections among malnourished children.42 This integrated approach demonstrates the importance of addressing both the nutritional and environmental determinants of health to enhance vaccine efficacy in vulnerable populations.

Community-Level Health Interventions

Community health interventions must target the environmental factors that contribute to poor vaccine efficacy. Improving sanitation, access to clean water, and promoting hygiene practices are essential for reducing the incidence of infections that further weaken the immune system. Deworming programs, for instance, can help reduce the burden of parasitic infections that exacerbate malnutrition and impair immune responses.

Integrated nutrition and vaccination campaigns should be prioritized. These campaigns can combine nutritional supplementation, deworming, and vaccination into a single intervention, addressing both malnutrition and immunity simultaneously. Such integrated campaigns have shown success in countries like Bangladesh, where vitamin A supplementation has been incorporated into routine immunization programs, leading to improved health outcomes for children.

Policy Recommendations

Policymakers should consider the following steps to improve vaccine efficacy in malnourished populations:

Integrated Program Design: Health ministries should design integrated programs that combine nutrition, sanitation, and vaccination efforts to target the root causes of poor vaccine efficacy. Flexible Vaccination Schedules: Immunization schedules should be flexible enough to accommodate the nutritional needs of children, with options for booster doses or delayed vaccinations where necessary. Increased Funding for Joint Programs: Global health organizations and donors should prioritize funding for programs that integrate nutrition with vaccination efforts. This funding should support not only vaccine delivery but also the provision of essential nutritional supplements and community health initiatives.Discussion

The findings from this review align with existing literature that highlights the significant impact of malnutrition on vaccine efficacy, particularly for oral vaccines like OPV and rotavirus. As confirmed in previous studies, malnourished children consistently exhibit lower seroconversion rates, largely due to impaired mucosal and systemic immunity. However, this review also contributes to the growing body of evidence by offering a comprehensive conceptual framework that integrates nutritional status, immune function, and environmental context to explain the reduced vaccine efficacy in malnourished populations.

Comparison to Previous Research

Previous research has demonstrated that vitamin A supplementation can enhance immune responses to vaccines, particularly for the measles vaccine. In Bangladesh, for example, integrated campaigns that included vitamin A supplementation were associated with a 25% improvement in measles seroconversion rates, which is consistent with the findings of this review.43 Similarly, studies from Kenya and Ethiopia confirm that providing booster doses of vaccines, especially in acutely malnourished children, can significantly improve antibody titers and immune protection.44

However, this review also highlights some important differences from previous research. While prior studies have focused primarily on individual vaccines or specific nutritional interventions, this review emphasizes the synergistic effects of malnutrition and poor environmental conditions on overall vaccine efficacy. The inclusion of environmental health interventions, such as WASH (Water, Sanitation, and Hygiene) programs, as a critical component of improving vaccine outcomes represents a broader approach to addressing the complex factors that undermine immunization success in LMICs. This integrated approach goes beyond traditional immunization programs by recognizing the importance of addressing both nutritional and environmental determinants of health.

Policy Implications

The results of this review have significant implications for public health policy, particularly in low-resource settings where malnutrition and poor vaccine efficacy continue to pose major challenges. Policymakers must prioritize integrated public health strategies that combine nutritional support with immunization programs. Specifically, the following policy steps are recommended:

Nutritional Supplementation and Immunization Programs: Governments and global health organizations should implement policies that integrate nutritional interventions, such as vitamin A, zinc, and iron supplementation, with routine immunization efforts. This approach has been proven to enhance vaccine efficacy and should be scaled up across LMICs. Flexible Immunization Schedules: Health systems should adopt flexible immunization schedules that allow for delayed vaccinations in severely malnourished children or provide booster doses to those who are unable to mount an adequate immune response initially. This will ensure that malnourished children receive full protection from vaccine-preventable diseases. Invest in WASH Programs: Policymakers should also invest in environmental health interventions, particularly in regions where poor sanitation and limited access to clean water exacerbate the effects of malnutrition. Integrating WASH programs with vaccination campaigns can enhance vaccine efficacy, especially for oral vaccines that rely on mucosal immunity. Cross-Sector Collaboration: National governments, non-governmental organizations, and international health bodies (eg, WHO, UNICEF) must work together to create multisectoral strategies that address both the nutritional and environmental factors contributing to poor vaccine efficacy. Cross-sector collaboration will be essential to ensuring that the policies implemented are sustainable and effective in the long term.Limitations

While this review provides a comprehensive overview of vaccine efficacy in malnourished populations, several limitations must be acknowledged:

Geographical and Contextual Limitations: Many of the studies included in this review were conducted in specific regions or countries within LMICs, which may limit the generalizability of the findings to other settings. For example, nutritional deficiencies and healthcare access may vary significantly between countries, influencing the observed vaccine efficacy. Recall Bias in Self-Reported Data: Several studies relied on self-reported vaccination data, particularly in rural settings where official vaccination records may not be consistently available. This introduces the potential for recall bias, where caregivers may inaccurately report their child’s vaccination history, leading to misclassification and potentially affecting the accuracy of seroconversion measurements. Variability in Diagnostic Criteria for Malnutrition: The studies used varying criteria to diagnose malnutrition, with some relying on anthropometric measures (eg, weight-for-height or height-for-age) and others using biomarkers to assess micronutrient deficiencies. This variability could introduce inconsistencies in how malnutrition was defined and may affect comparisons across studies. Limited Longitudinal Data: Most of the studies included were cross-sectional, measuring immune responses at a single point in time. Longitudinal studies that track the long-term effects of malnutrition on vaccine-induced immunity are limited. Future research should aim to fill this gap by conducting studies that follow malnourished children over time to assess how sustained nutritional interventions impact their immune responses to vaccines. Focus on Children: This review focused specifically on children due to their unique nutritional needs and vulnerability to vaccine-preventable diseases. While this enhances the relevance of the findings for child immunization programs, the results may not be applicable to other vulnerable populations, such as pregnant women or the elderly.Key Recommendations Nutritional Interventions: Incorporating routine nutritional screening and supplementation into vaccination programs could significantly improve vaccine responses. Providing vitamin A and zinc alongside vaccines has shown promising results in boosting immune responses in malnourished children. Flexible Vaccination Schedules: Adjusting immunization schedules to allow for the administration of booster doses in malnourished children or delaying vaccination until nutritional status improves could help overcome the immune deficits caused by malnutrition. Community Health Interventions: Addressing environmental factors through community-based health interventions, such as improving access to clean water and promoting sanitation, could reduce the burden of infections that exacerbate malnutrition and further weaken immune function.Implications for Future Research and Practice Research Directions

Further research is needed to refine our understanding of how specific forms of malnutrition impact vaccine efficacy. Studies should explore the optimal timing of vaccinations for malnourished children, as well as the most effective dosing strategies.45–47 Clinical trials that combine nutritional supplementation with vaccines will provide valuable insights into how best to enhance immune responses in malnourished populations.

Moreover, future research should examine the long-term effects of malnutrition on immunity and vaccine efficacy, particularly in relation to booster doses and waning immunity over time.

Practical Applications

The proposed conceptual framework can be used by healthcare providers and public health officials to design more effective vaccination programs for malnourished populations. By integrating nutrition assessments and interventions into immunization campaigns, healthcare providers can ensure that children receive both the nutritional support and vaccines they need to build strong immune defenses.

Global health organizations, such as WHO and UNICEF, can adopt the framework to guide the design of vaccination strategies that account for the nutritional and environmental contexts of children in LMICs. This will improve vaccine efficacy and ultimately reduce the burden of vaccine-preventable diseases in malnourished populations.

Conclusion

This review presents a novel conceptual framework that integrates nutritional status, immune function, and environmental context to explain the reduced vaccine efficacy in malnourished populations. While existing studies have explored the individual impacts of malnutrition on specific vaccines, this framework offers a more holistic approach by highlighting the synergistic effects of malnutrition, compromised immune responses, and poor living conditions on vaccine outcomes. By addressing these factors collectively, this framework fills a critical gap in the literature, providing a comprehensive understanding of the multiple determinants that contribute to poor vaccine efficacy in low- and middle-income countries (LMICs).

The review also emphasizes the need for integrated public health strategies that go beyond simply administering vaccines to malnourished children. It underscores the importance of combining nutritional interventions (such as vitamin A supplementation and deworming programs) with flexible immunization schedules and environmental health improvements to optimize vaccine outcomes. This approach not only improves the likelihood of seroconversion but also ensures long-term protection against vaccine-preventable diseases in vulnerable populations.

In addressing these challenges, this framework provides several important contributions to the field:

It highlights the disproportionate effects of malnutrition on oral vaccines, which rely on mucosal immunity, compared to injectable vaccines. It demonstrates the importance of flexible immunization schedules that adapt to the nutritional status of the child, allowing for booster doses and delayed vaccinations where necessary. It stresses the role of environmental interventions, such as WASH programs, in improving vaccine efficacy by addressing the underlying factors that contribute to poor health outcomes.Call to Action

Given the clear evidence that malnutrition significantly impairs vaccine efficacy, global health organizations, governments, and policymakers must act swiftly to address this urgent issue. Global health organizations such as the World Health Organization (WHO), UNICEF, and Gavi should prioritize the integration of nutrition and immunization programs to reduce the burden of vaccine-preventable diseases in malnourished populations. In particular, efforts should focus on:

Scaling up nutritional interventions such as vitamin A supplementation, zinc fortification, and deworming programs, integrated with routine immunization campaigns in LMICs. Implementing flexible vaccination schedules that accommodate the needs of malnourished children by providing booster doses or delaying certain vaccines until nutritional status improves. Investing in WASH programs to improve sanitation, access to clean water, and overall living conditions, which are critical for ensuring the success of vaccination efforts, especially for oral vaccines.Future Directions

To further strengthen the evidence base and refine policy interventions, future research should focus on:

Longitudinal studies that track the impact of sustained nutritional interventions on vaccine efficacy over time. Trials in diverse LMIC contexts to explore the generalizability of these interventions across different populations and settings. Further exploration of environmental factors, such as the role of environmental enteropathy, in reducing vaccine efficacy, with a view toward integrating these findings into public health strategies.

By adopting these integrated approaches, global health organizations and policymakers can significantly improve vaccine efficacy and protect the most vulnerable populations from preventable diseases. This comprehensive framework provides a roadmap for more effective immunization strategies that address not just the biological but also the socio-environmental determinants of vaccine efficacy in malnourished populations.

Acknowledgments

The authors extend their sincere gratitude to the Ministry of Health of the Democratic Republic of Congo and the Provincial Health Authorities for their continuous support. We would also like to thank the various organizations and individuals whose valuable contributions and expertise have significantly enriched this research.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Disclosure

The authors declare that they have no conflicts of interest.

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