A Prioritised Research Agenda to Inform the Introduction and Use of Lassa fever vaccines in West Africa

Abstract

Objective

Lassa fever is a viral haemorrhagic disease endemic in West Africa. While several vaccine candidates are in development, evidence to guide policy- and decision-making on vaccines remains limited. We convened a Policy Research Working Group (PRWG) to develop a prioritised research agenda to reduce delays related to policy- and decision-making.

Methods

Using the Child Health and Nutrition Research Initiative (CHNRI) methodology, we conducted a two-phase prioritisation exercise. First, a rapid assessment of literature and expert interviews was conducted to identify evidence gaps, which were refined into 29 questions across four thematic categories. In phase two, 235 experts scored these questions using five criteria.

Results

Research Priority Scores (RPS) ranged from 80-92%, indicating the importance of the identified research questions. Thirteen research questions were prioritised, focusing on defining vaccination target groups, assessing vaccine efficacy in special populations, evaluating economic impact, and understanding vaccine acceptance. High expert agreement (67-85%) reinforced the robustness of the prioritisation outcomes.

Conclusions

This stakeholder-driven agenda highlights the most critical evidence needs to guide vaccination policies, national decision-making, and implementation planning for future Lassa fever vaccines. Early alignment between research and policy can accelerate vaccine introduction and ensure equitable access in endemic regions.

INTRODUCTION

Lassa fever is an acute viral haemorrhagic illness that is largely transmitted through exposure to rodent excreta with occasional human-to-human transmission. Lassa fever is endemic in West Africa and is projected to spread to other parts of Africa due to dynamic changes in environmental conditions1. Recent modelling suggests that approximately 897,700 Lassa fever cases occur annually, although most remain undetected because symptoms are mild or absent 2. Severe disease requires hospitalisation with case fatality rates of up to 20% 1,3. Women in late stages of pregnancy face higher risks with case fatality rates that can exceed 30% and foetal loss in up to 75% 4,5.

Despite this burden, no licensed vaccines currently exist; however, one may be available after 2030 5. As vaccine development progresses, countries require evidence to support policy- and decision-making. Two Lassa fever research agendas have been published, but these focus on virology, diagnostics, therapeutics, and vaccine development rather than policy- and decision-making for vaccine implementation 6,7. Thus, to address these gaps, we developed a prioritised research agenda using the Child Health and Nutrition Research Initiative (CHNRI) methodology. The process was overseen by the Lassa fever Policy Research Working Group (PRWG) 8–10. The PRWG members are experts spanning regional public health authorities, national disease control programmes, research institutions, and global health partners and funders.

This study presents the first structured, regionally grounded research agenda specifically focused on supporting timely and evidence-informed vaccine introduction in Lassa-endemic countries.

METHODOLOGY

We used the CHNRI methodology, which provides a transparent and structured approach to research priority setting. This method clearly defines the context and criteria, ensures that all inputs and decisions are documented and auditable, employs a structured scoring system, and builds consensus and ownership through broad stakeholder engagement 11.

We carried out the research prioritisation process in two phases. Phase 1 identified and finalised the research questions and defined the context and criteria, while Phase 2 scored and prioritised the questions.

Phase 1

1. Finalising the list of research questions.

To identify the research questions, we conducted a rapid assessment of published literature available from PubMed that was supplemented with unpublished documents provided by CEPI and WAHO. Additional evidence gaps were identified through stakeholder interviews with experts knowledgeable about Lassa fever.

Rapid assessment of literature

We conducted searches on August 1, 2023 and September 23, 2024, using R version 4·3·2 and the packages pubmedR and rentrez with the search query ("Lassa virus"Title/Abstract OR "Lassa fever"Title/Abstract) AND ({the last 5 years}), resulting in 663 articles 12–14.

We extracted and categorised metadata from all records. Each record was then reviewed to remove duplicate titles, assign a regional location (within or outside Africa), and classify studies based on selected terms in the abstract (e.g., disease focus, animal focus, policy, vaccine and treatment, and implementation).

We excluded articles if they did not include human subjects, as well as laboratory-based, preclinical, or narrowly focused studies and case reports. Errata were excluded, and original publications were reviewed where necessary. This process resulted in 182 articles, with an additional 18 identified through bibliography searches.

Articles were then prioritised based on title, type, and relevance to policy and implementation into three levels of “high” (n=60), “moderate” (n=51) and “low” (n=89). High priority articles focused on vaccine policy, strategic planning, official recommendations, or human epidemiology with emphasis on at-risk populations. Moderate priority articles focused on immunological studies, outbreak reports, or surveillance methodologies. Low priority articles included those considered overly generic or narrowly focused, such as commentaries, specific clinical practices, or repetitive outbreak descriptions. After the processing in R, we exported the list of records to Microsoft Excel. The data file is available from supplemental file 1.

An initial full-text review was conducted for the 60 articles classified as “high” by two independent team members. In addition to peer-reviewed articles, the review included unpublished literature shared by CEPI and WAHO, such as internal gap analyses, CEPI's Target Product Profiles, and meeting minutes from regional consultations. Relevant content was extracted into Excel. Forty-two evidence gaps were identified after removing duplicates and questions not relevant to our research agenda.

Interviews

To supplement the rapid assessment of literature, we conducted semi-structured interviews with subject matter experts in Lassa fever, who were identified via discussions with WAHO and CEPI. We contacted ten experts, of whom eight consented to participate. Interviews were guided by a discussion framework developed in advance to ensure consistency across participants. We synthesised the qualitative data and identified 41 evidence gaps.

Finalisation of research questions

We reviewed all 83 evidence gaps and generated 34 research questions, after removing questions already being addressed via other studies (e.g., clinical trials or the Enable study). We shared the list for review with various stakeholders and the Lassa fever PRWG for their feedback. Considering the feedback, we finalised 29 research questions for prioritisation. The questions were categorised into four topical areas: (i) epidemiology-related (n=12), (ii) likely to require data generated from a vaccine trial (n=9), (iii) requiring economic impact or modelling work (n=4), and (iv) uptake and acceptance (n=4).

2. Adapting the CHNRI methodology to define context and criteria

We developed the draft research context and pre-selected eight potential scoring criteria to prioritise the research questions, as required by the CHNRI method 8. The proposed context and criteria were discussed with the PRWG, which chose five criteria. The agreed-upon context and selected scoring criteria are shown in Table 1.

Context	Description
Who (population of interest)	All stakeholders who may hold policy and decision-making responsibilities related to Lassa fever vaccine introduction and implementation.a
Where (geographical scope of research)	Global, West African region and national country levels.b
When (Time scale)	Present day to 2030c
What outcome (Proposed impact of interest)	Evidence-based policy and decision-making on the use of Lassa fever vaccines
Criteria, alphabetically	Description
Answerability	Do you believe it is possible to answer this question through research?
Effect on equity	Do you believe that the research question and its outputs will contribute to reducing inequities in health?
Potential for translation	Do you believe that the research question and its outputs will likely be translated into evidence-based policy and decision-making on Lassa fever in West Africa?
Relevance to context	Will the research question and its outputs contribute to addressing relevant evidence gaps related to policy and decision-making on Lassa fever in West Africa?
Feasibility within context	Do you believe designing and conducting the proposed research in the communities most affected by Lassa fever is feasible?

Table 1
Adapted CHNRI context and criteria used to guide research prioritisation for Lassa fever vaccine policy and decision-making.

Notes:
a: While the research agenda will not focus on implementation, we have included stakeholders involved in implementation since their views remain important to policy- and decision-makers.

b: Given the early stage of vaccine development, it is essential to capture potential policy implications at the global, regional, and national levels.

c: The Lassa fever vaccine is anticipated to become available to countries by 2030 or earlier.

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Phase 2

In this phase, we used the CHNRI methodology to prioritise the research questions. We developed an online survey tool using Qualtrics™ to score the 29 research questions within the defined context and the scoring criteria (Table 1). The survey included three demographic questions on geographical location, organisational affiliation, and familiarity with the Lassa fever. We used the demographic details to conduct stratified analyses. We randomised the order of the research questions across participants to minimise response-order effects and reduce fatigue-related bias.

We asked respondents to score each research question against the five scoring criteria (Table 1) either as “Yes”, “No”, or “Maybe”, which we assigned scores of 1, 0, and 0·5, respectively. Respondents could select “don’t know” for questions outside their area of expertise; these responses were excluded from the analyses.

We shared an anonymous link to complete the survey with 112 individuals identified for their expertise or work relevant to the Lassa fever area. We also provided access to the list of research questions for scoring via a Microsoft Excel file, facilitating the offline completion of the survey. We asked PRWG members to circulate the survey or Excel file to any stakeholders who may be interested in providing their feedback. The survey remained open for approximately 1 month. We downloaded and included the data from both completed and partially completed surveys (response provided to at least one research question) into Microsoft Excel from Qualtrics™. We calculated the research priority scores (RPS) with 95% confidence intervals, and average expert agreement (AEA) for each research question following the CHNRI methodology. (Supplemental file 2)

Finally, we conducted six stratified analyses considering various levels of Lassa fever knowledge, geographical location (Nigeria or other), and government employment.

RESULTS

Respondent characteristics

A total of 235 respondents participated in scoring the research questions; of these 155 (66%) fully completed the survey, and 80 (34%) provided partial responses (Table 2).

Organisation type	Number	Percentage
Government agency or department	126	54%
Academic institution or research institution	45	19%
Civil society or non-governmental organisation	35	15%
UN agency	9	4%
Othera	20	9%
Total	235	100%
Lassa fever familiarity	Number	Percentage
A great deal	65	28%
A lot	83	35%
A moderate amount	59	25%
A little	25	11%
No response	1	0%
None	2	1%
Total	235	100%
Country	Number	Percentage
Nigeria	143	61%
Gambia	16	7%
Guinea	14	6%
Benin	12	5%
Burkina Faso	8	3%
Côte d'Ivoire	6	3%
Mali	5	2%
Senegal	5	2%
Liberia	4	2%
Ghana	3	1%
Switzerland	3	1%
Togo	2	1%
United States of America	2	1%
Otherb	12	5%
Total	235	100%

Table 2
Demographic characteristics and Lassa fever familiarity of survey respondents (n = 235). Values are presented as number (N) and percentage (%).

Notes:
a: Other includes regional health institutions

b: Includes one respondent each from Canada, Ethiopia, Gabon, Germany, Guinea-Bissau, Haiti, Japan, Rwanda, Sierra Leone, South Africa, Uganda, and Zimbabwe.

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Most respondents were based in Africa, with 143 respondents from Nigeria (93 complete and 50 partial) (Table 2). Six respondents were based outside of the African continent in North America, Europe, and Asia. Over half of the respondents reported affiliation with a government agency or department, while more than 60% reported being quite familiar with Lassa fever.

Overall results

For the aggregated survey response, the RPS range was relatively narrow, with scores ranging from a low of 80% to a high of 92% for the 29 research questions (Table 3).

Research question	Category	RPS	95% CI (LB)	95% CI (UB)	AEA
What are the appropriate factors to identify target groups for vaccination?	Epidemiological	92%	89%	94%	85%
Are there specific co-morbidities that increase the risk of severe disease, sequelae, and death?	Epidemiological	91%	89%	93%	85%
What is the economic impact of Lassa fever and its control strategies in the high burden countries?	Economic impact	91%	89%	93%	84%
What are most effective communication strategies to improve vaccine acceptance and demand?	Uptake & acceptability	91%	88%	93%	84%
Does the community recognize Lassa fever and its sequelae?	Uptake & acceptability	90%	88%	93%	82%
What is the efficacy of the vaccine in immunocompromised or malnourished individuals?	Vaccine clinical trial	90%	87%	92%	82%
What is the impact and cost effectiveness of reactive and preventive vaccination strategies?	Economic impact	90%	87%	92%	82%
What is the age-specific acceptability of vaccination to prevent Lassa fever?	Uptake & acceptability	90%	87%	92%	82%
Can the vaccine be co-administered with other vaccines used in routine childhood immunization or as part of multi-antigen preventive campaigns?	Vaccine clinical trial	90%	87%	92%	82%
What is the health and economic benefit of implementing Lassa fever vaccines in comparison to other preventive and therapeutic interventions?	Economic impact	89%	87%	92%	81%
What is the age-specific efficacy of the vaccine?	Vaccine clinical trial	89%	87%	92%	81%
What is the balance of risks and benefits of vaccination in different target populations?	Economic impact	89%	86%	92%	81%
What, if any, are the risk factors for re-infection of Lassa fever?	Epidemiological	89%	86%	91%	80%
In areas where there is predominantly human-to-human transmission does the vaccine provide herd immunity?	Vaccine clinical trial	89%	86%	91%	80%
What is the acceptability of vaccination to prevent Lassa fever during child bearing years and during pregnancy?	Uptake & acceptability	88%	85%	91%	79%
What are the appropriate diagnostics to estimate vaccine effectiveness and impact?	Vaccine clinical trial	88%	86%	91%	79%
What proportion of cases are a result of mother-to-child transmission?	Epidemiological	88%	85%	91%	79%
Does the efficacy of the vaccine differ between naïve populations (including travelers to endemic areas) and those with pre-existing antibodies and/or previous infection?	Vaccine clinical trial	88%	85%	90%	78%
What proportion of cases are a result of human-to-human transmission?	Epidemiological	88%	85%	90%	80%
Does the seasonality of the disease influence vaccination strategy?	Epidemiological	88%	84%	90%	80%
Can the vaccination of women during child bearing years and pregnant women provide protection during infancy?	Vaccine clinical trial	88%	85%	90%	77%
Does vaccine efficacy or effectiveness vary between different virus genotypes?	Vaccine clinical trial	87%	84%	90%	78%
What is the duration of protection following natural infection?	Epidemiological	87%	84%	89%	77%
What is the duration of Lassa fever viral persistence in body fluids (e.g., semen, breast milk, ocular fluids, saliva, tears)?	Epidemiological	86%	83%	89%	78%
Is the severity of disease lower following re-infection?	Epidemiological	85%	82%	88%	75%
For human-to-human transmission, what is the reproductive number (R0)?	Epidemiological	84%	81%	88%	74%
What are the differences in the severity of disease caused by different lineages?	Epidemiological	84%	81%	87%	73%
What is the age-specific exposure rate to the Lassa fever virus in children?	Epidemiological	84%	80%	87%	74%
What is the probability of Lassa virus reactivation from sanctuary sites within the body after initial recovery?	Epidemiological	80%	76%	83%	67%

Table 3
Ranking of 29 Research Questions across all Respondents' Research Priority Score (RPS) and Average Expert Agreement (AEA) n=235.

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The narrow range suggests respondents considered most research questions as highly important. The AEA ranged from 67% to 85%, indicating moderate to high agreement, with higher agreement scores for research questions with higher RPS. This suggests that when a research question was recognised as a high priority (high RPS), respondents tended to agree on its prioritisation (high AEA).

Stratified analyses

To explore skew and possible biases, we conducted six stratified analyses based on knowledge, geography, and employment (i) extremely knowledgeable (n=65); (ii) with very high level of knowledge (n=148); (iii) with moderate or greater level of knowledge (n=207); (iv) from Nigeria (n=143); (v) from countries other than Nigeria (n=92); and (vi) employees of national governments (n=126). The stratified analysis shows strong agreement in RPS for all respondents, as well as those with moderate to extremely high knowledge of Lassa fever, indicating that their priorities were similar (Table 4)

Research question	Category	All responses	Gov't only	Moderate, Very, & Extremely knowledgeable	Very & Extremely knowledgeable	Extremely knowledgeable only	All countries but Nigeria	Nigeria only
		N=235	N=126	N=207	N=148	N=65	N=92	N=143
What are the appropriate factors to identify target groups for vaccination?	Epidemiological	92%	91%	92%	93%	95%	92%	92%
Are there specific co-morbidities that increase the risk of severe disease, sequelae, and death?	Epidemiological	91%	91%	93%	94%	94%	90%	92%
What, if any, are the risk factors for re-infection of Lassa fever?	Epidemiological	89%	90%	88%	89%	87%	88%	89%
What proportion of cases are a result of mother-to-child transmission?	Epidemiological	88%	87%	89%	89%	89%	88%	88%
What proportion of cases are a result of human-to-human transmission?	Epidemiological	88%	89%	89%	89%	90%	86%	89%
Does the seasonality of the disease influence vaccination strategy?	Epidemiological	88%	89%	88%	88%	91%	85%	89%
What is the duration of protection following natural infection?	Epidemiological	87%	88%	87%	89%	88%	84%	89%
What is the duration of Lassa fever viral persistence in body fluids (e.g., semen, breast milk, ocular fluids, saliva, tears)?	Epidemiological	86%	88%	86%	87%	88%	82%	89%
Is the severity of disease lower following reinfection?	Epidemiological	85%	86%	87%	87%	85%	84%	86%
For human-to-human transmission, what is the reproductive number (R0)?	Epidemiological	84%	85%	84%	85%	85%	80%	87%
What are the differences in the severity of disease caused by different lineages?	Epidemiological	84%	85%	84%	85%	89%	85%	84%
What is the age-specific exposure rate to the Lassa fever virus in children?	Epidemiological	84%	84%	84%	85%	84%	84%	84%
What is the probability of Lassa virus reactivation from sanctuary sites within the body after initial recovery?	Epidemiological	80%	84%	79%	80%	79%	74%	84%
What is the efficacy of the vaccine in immunocompromised or malnourished individuals?	Vaccine clinical trial	90%	90%	91%	93%	93%	87%	92%
Can the vaccine be co-administered with other vaccines used in routine childhood immunisation or as part of multi-antigen preventive campaigns?	Vaccine clinical trial	90%	90%	90%	90%	88%	90%	89%
What is the age-specific efficacy of the vaccine?	Vaccine clinical trial	89%	90%	90%	90%	92%	90%	89%
In areas where there is predominantly human-to-human transmission, does the vaccine provide herd immunity?	Vaccine clinical trial	89%	89%	89%	89%	89%	89%	88%
What are the appropriate diagnostics to estimate vaccine effectiveness and impact?	Vaccine clinical trial	88%	89%	89%	89%	90%	89%	87%
Does the efficacy of the vaccine differ between naïve populations (including travellers to endemic areas) and those with pre-existing antibodies and/or previous infection?	Vaccine clinical trial	88%	88%	89%	90%	91%	86%	89%
Can the vaccination of women during childbearing years and pregnant women provide protection during infancy?	Vaccine clinical trial	88%	88%	88%	89%	88%	88%	87%
Does vaccine efficacy or effectiveness vary between different virus genotypes?	Vaccine clinical trial	87%	89%	88%	87%	86%	88%	87%
What is the economic impact of Lassa fever and its control strategies in the high-burden countries?	Economic impact	91%	89%	92%	93%	95%	91%	91%
What is the impact and cost-effectiveness of reactive and preventive vaccination strategies?	Economic impact	90%	89%	90%	91%	91%	88%	91%
What is the health and economic benefit of implementing Lassa fever vaccines in comparison to other preventive and therapeutic interventions?	Economic impact	89%	89%	91%	93%	93%	87%	91%
What is the balance of risks and benefits of vaccination in different target populations?	Economic impact	89%	90%	90%	91%	92%	86%	92%
What are most effective communication strategies to improve vaccine acceptance and demand?	Uptake & acceptability	91%	91%	91%	92%	93%	90%	91%
Does the community recognise Lassa fever and its sequelae?	Uptake & acceptability	90%	89%	91%	92%	92%	90%	91%
What is the age-specific acceptability of vaccination to prevent Lassa fever?	Uptake & acceptability	90%	91%	90%	90%	89%	89%	90%
What is the acceptability of vaccination to prevent Lassa fever during childbearing years and during pregnancy?	Uptake & acceptability	88%	88%	89%	90%	90%	87%	89%

Table 4
Stratified analysis of research question prioritisation by respondent characteristics, including organisation type, level of expertise, and geographic location. Values represent Research Priority Scores (RPS) as percentages.

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Prioritised questions

Based on PRWG feedback, we used two complementary approaches to prioritise research questions. First, we combined the top 10 priorities from all respondents with the top 10 identified by government representatives. This ensured that the full range of stakeholder views was captured while giving appropriate weight to government perspectives. Government perspectives were prioritised as they are central to policy uptake, are primary users of evidence, and are likely to prioritise research questions differently from other stakeholders. This approach yielded 13 prioritised questions. Second, we selected the top three questions within each thematic category. This method ensured balance across domains and increased the likelihood that priorities would align with the interests of diverse research funders, who often support specific thematic areas. This approach produced 12 prioritised questions. Together, these methods produced a set of 13 priorities that reflect stakeholder perspectives and are responsive to policy and funding contexts. (Table 5).

Research question	Category	RPS n=235	Ranking
What are the appropriate factors to identify target groups for vaccination?	Epidemiological	92%	1
Are there specific co-morbidities that increase the risk of severe disease, sequelae, and death?	Epidemiological	91%	2
What, if any, are the risk factors for re-infection of Lassa fever?	Epidemiological	89%	10
What is the efficacy of the vaccine in immunocompromised or malnourished individuals?	Vaccine clinical trial	90%	5
Can the vaccine be co-administered with other vaccines used in routine childhood immunisation or as part of multi-antigen preventive campaigns?	Vaccine clinical trial	90%	6
What is the age-specific efficacy of the vaccine?	Vaccine clinical trial	89%	11
What is the economic impact of Lassa fever and its control strategies in the high-burden countries?	Economic impact	91%	3
What is the impact and cost-effectiveness of reactive and preventive vaccination strategies?	Economic impact	90%	7
What is the health and economic benefit of implementing Lassa fever vaccines in comparison to other preventive and therapeutic interventions?	Economic impact	89%	12
What is the balance of risks and benefits of vaccination in different target populations?	Economic impact	89%	13
What are most effective communication strategies to improve vaccine acceptance and demand?	Uptake & acceptability	91%	4
Does the community recognise Lassa fever and its sequelae?	Uptake & acceptability	90%	8
What is the age-specific acceptability of vaccination to prevent Lassa fever?	Uptake & acceptability	90%	9

Table 5
Final prioritised research questions ranked by Research Priority Score (RPS) among survey respondents (n = 235).

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In summary, four questions focus on economic and impact modelling work, three questions aim to improve epidemiological understanding, three focus on vaccine-associated clinical parameters, and three address vaccine uptake and acceptance. Questions that were more scientifically complex or exploratory (e.g., questions about viral reactivation in sanctuary sites or lineage-specific disease severity) received lower RPS scores. In contrast, those with clear policy implications, such as economic impact, received higher RPS.

DISCUSSION

Evidence to guide policy- and decision-making for Lassa fever vaccines remains limited. This study addresses that gap by generating a structured, context-specific research agenda, co-created with national stakeholders and grounded in existing evidence.

Thirteen research questions emerged as high-priority for supporting future Lassa fever vaccine policy- and decision-making. We employed a hybrid prioritisation approach that balanced multiple stakeholder perspectives and considered thematic categories.

Delayed identification of research needs can postpone vaccine implementation. For example, the RTS,S malaria vaccine took nearly a decade from market authorisation to the first national introduction and required large-scale pilots to address feasibility and impact and assess safety signals 15–18. Timely identification of policy and decision-making needs is critical and can accelerate global, regional, or national decision-making (e.g., WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization or National Immunization Technical Advisory Groups).

Research priorities for Lassa fever have focused on virology, diagnostics, therapeutics, and vaccine development 6,7,19. Reports describing research priorities to support policy and decision-making for vaccine implementation at the country or regional level were limited. One WHO report on Lassa fever identified two areas for policy guidance on vaccination strategies for various target populations, geographic regions, and epidemiological scenarios, as well as for community sensitisation to vaccine acceptance and promotion within the community 7.

Other country-level studies, such as one in India, used the CHNRI method and identified 15 priority research options for 11 zoonotic diseases in India 20. Others used more qualitative methods (e.g., Delphi) and disease reference groups comprising ∼15 experts for zoonotic diseases 20–22. Depending on the disease, these research areas were broad, and none focused on research questions to support policy- and decision-making related to vaccine implementation, nor did they specify priority research questions for conducting specific research.

The relatively narrow RPS range is somewhat distinct from other CHNRI exercises. This difference could be related to the number of research questions assessed in an exercise or due to the number of respondents. We reviewed several CHNRI exercises conducted in the past 15 years on diverse topics, which did not show any influence from the number of questions or respondents (Panel 1). Therefore, it is reasonable to assume that our respondents collectively considered all research questions as important.

A key strength was the high-level engagement of PRWG members and WAHO, which likely contributed to robust participation in the prioritisation exercise (n=235). Additionally, 54% of the respondents identified themselves as government representatives, a group that is often underrepresented in similar exercises. This strong representation of government stakeholders supports the validity and relevance of the prioritised questions.

While CHNRI exercises do not mandate a specific sample size, evidence suggests that the collective opinion of a group of 45-55 experts stabilises and reliably identifies research priorities 23. Given our larger sample size, we are confident that the research priorities reflect the views of both government functionaries and technical experts.

Panel 1: Examples of CHNRI research priority exercises with a variable number of research questions (RQs) and respondents

• Brennan-Wilson A et al: 26 RQs were prioritised by 143 experts with an RPS range of 69% to 83% 24.

• George A et al: 55 RQs were prioritised by 29 experts with an RPS range of 56 to 86% 25.

• Sekar N et al: 103 research options were scored by five experts with an RPS of 34% to 95% 20.

• Rudan I et al: 158 RQs were scored by 45 experts with an RPS range of 29% to 79·7% 11.

• Yoshida S et al: 205 RQs were scored by 91 experts with an RPS of 47% to 90% 26.

• Ko M et al: 93 RQs scored by 138 experts with an RPS of 65·7% to 88·8%27.

• Wazny K et al: 466 RQs scored by 98 experts with an RPS range of 37% to 95% 28.

• Arora NK et al: A broad country-level exercise on maternal, newborn, child health and nutrition research priorities in which 373 RQs were scored by 893 experts with an overall RPS range of 48% to 93% 29.

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A limitation of this study is that we conducted a small number of expert interviews (n=8) during the question-generation phase. While this may have constrained the breadth of perspectives captured, the interviews were designed to complement a comprehensive literature review of over 200 published and unpublished sources. Furthermore, the identified evidence gaps and draft research questions were iteratively refined through consultation with the PRWG. This limitation was partly mitigated by the subsequent large-scale prioritisation exercise involving 235 respondents from diverse institutional and geographic backgrounds.

Another potential limitation is the over-representation of respondents from Nigeria (61%), which could introduce geographic bias. Although this reflects Nigeria’s disproportionately high share of the Lassa fever burden, potential biases could result, stemming from the different epidemiology of Lassa fever in Nigeria relative to other West African countries. However, the stratified analyses did not indicate a geographical bias due to the higher proportion of respondents from Nigeria. We found no evidence of under-prioritisation of research questions relevant to countries neighbouring Nigeria, where Lassa fever is not endemic, but may nevertheless be at risk. This indicates that the results are generalisable to other Lassa-affected settings.

The CHNRI methodology has inherent limitations as the process depends on a set of criteria without a qualitative explanation. This can result in oversimplifying complex perspectives 11,30. A hybrid approach with more qualitative activities (e.g., interviews, focus groups) could provide a stronger rationale for the selection of the prioritised research questions. However, the high AEA for the high-priority research questions suggests consistency. Finally, CHNRI produces a one-time priority list, which may need to be revisited if evidence, policy priorities, and product development significantly evolve.

CONCLUSIONS

As vaccine development advances, the prioritised research agenda provides a roadmap for aligning evidence generation with the needs of policy- and decision-makers at national, regional, and global levels. The next step is to translate these priorities into funded research projects, multi-country studies, and implementation pilots. Mechanisms will also be needed to monitor progress and ensure findings inform policy in real time.

WAHO played a central role in developing this research agenda and will continue to support its implementation by embedding these priorities within a comprehensive regional R&D plan, and by coordinating, tracking, and sharing the results of multisectoral research activities. National governments and key policy-making bodies should stay informed of emerging evidence to guide their timely decision-making. Finally, funding agencies and research institutions should align investments with this agenda, while ensuring complementarity with ongoing and planned research.

By fostering early collaboration across key stakeholders, this agenda can help ensure that essential evidence is available when needed, ultimately accelerating safe, equitable, and evidence-informed vaccine introduction.

Disclaimer

The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated.

Funding

This study was funded by the Coalition for Epidemic Preparedness Innovations (CEPI) to MMGH Consulting GmbH. CEPI provided input on interpretation of results and oversight of the project, but had no role in data collection or analysis.

Competing interests

MK, TC, and MR are employed at MMGH Consulting GmbH. SQ serves as an independent consultant to MMGH Consulting GmbH.

Ethics approval and consent to participate

This study involved expert interviews and survey-based prioritisation and did not include human subjects research requiring formal ethics approval. Participation was voluntary, and informed consent was obtained from all respondents. Data were anonymised before analysis to protect participant confidentiality.

Author contributions

• Conceptualisation: MK, SQ, TC
• Methodology and Study Design: MK, VL, SQ, TC, ABU, OO, CA, SS, YA, RA, DA, DB, CD-N, SD, IE, AL, KR, IS
• Data Collection: MK, MR
• Data Analysis: MK, MR
• Data Access and Maintenance: OO, CA, MK, TC, MR
• Interpretation of Results: MK, VL, SQ, TC, ABU, OO, CA, SS, YA, RA, DA, DB, CD-N, SD, IE, AL, KR, IS
• Writing – Original Draft: MK, SQ, TC
• Writing – Review & Editing: All authors
• Supervision: OO, IS

Data sharing statement

The data that support the findings of this study, including survey responses and full scoring datasets, are available from the corresponding author upon reasonable request, subject to agreements ensuring participant confidentiality.

Declaration of competing interest

Melissa Ko, Thomas Cherian, and Manuela Runge are employees of MMGH Consulting GmbH. Shamim Qazi is an independent consultant for MMGH Consulting GmbH. This study was funded by the Coalition for Epidemic Preparedness Innovations (CEPI). The funder had no role in data collection or analysis. All other authors declare no competing interests.

Acknowledgements

The authors would like to thank all the stakeholders who contributed their valuable time and insights during the consultations and the 235 experts who participated in the CHNRI exercise. Their perspectives were essential in shaping the findings and recommendations presented in this manuscript. We would also like to acknowledge Herolinda Musa for her support in setting up the Qualtrics survey. The authors acknowledge the use of ChatGPT (OpenAI, model GPT-5·1, accessed in November 2025) to assist with improving the readability of selected sections of this manuscript. The model was prompted with queries such as: “Can this text be improved for clarity and readability?” and “Please edit the manuscript to UK English.” AI use was limited exclusively to language refinement and did not involve data analysis, interpretation, or scientific conclusions. All AI-generated suggestions were reviewed, edited, and verified by the authors, who retained full oversight and responsibility for the final manuscript.

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