Safety and Immunogenicity of an rVSV Lassa Fever Vaccine Candidate.
Malkin E, Zaric M, Kieh M, Baden LR, Fitz-Patrick D, Marini A, Yun H, Hayes P, Bromell R, Ayorinde M, Fernandez N, Varma R, Sigei F, Ward M, Pindolia H, Sewell S, Amini F, Blie J, Wilson B, Faley P, McCullough J, Tokpah F, Wisseh C, Towalid E, Hadawale S, Sayeed E, Hunt D, Keshavarzi N, Barin B, Maljkovic Berry I, Parks CL, Truter SG, Walker K, Vekemans J, Lehrman J, Engelbrecht M, Malherbe M, Laufer D, Philiponis V, Higgs E, Mutua G, Fast PE, Gupta SB, rVSVΔG-LASV-GPC Study Group
- DOI
- 10.1056/NEJMoa2501073
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-20
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/a8a34f73-cb3d-4396-a2b0-7b28ee8a0156 is authoritative.
How this rating was calculated
- StatisticsStatistic did not reproduce−0.5★
- IntegrityIntegrity concern−0.5★
- ReportingEthical approvals partially met−0.25★
- ReportingData & code availability partially met−0.25★
- No data or code availability links were detected to verify.
- 01Printed percentage does not match its own count
20% does not match the reported count 2/20
“20.0% (2/20)”
Vaccine Safety and ReactogenicityFind in source
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
This Phase 1 trial is methodologically sound with clear randomization, blinding, and appropriate statistical reporting for an early-phase study. The main weaknesses are missing explicit ethics committee details, informed consent description, and a data availability statement, along with minor reporting gaps such as unspecified statistical software and randomization method.
Both reviewers agreed on study type (interventional) and on most dimensions; they diverged on ethical approvals (pass vs. warn), where the more conservative warn was adopted due to missing explicit IRB name and informed consent. The statistics verification component checked only 1 test (inconsistent), so statistical correctness beyond that is unverified.
Numerical inconsistencies
2 findings · worst highValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
- Internal contradictions in the reported numbersAssessed
1 reported summary statistic mathematically impossible for the stated N (PERCENT).
- PERCENT20% does not match the reported count 2/20
“20.0% (2/20)”
Vaccine Safety and ReactogenicityFind in source
- lowinternal contradictionThe abstract states 114 healthy adults were randomized, but the results section reports 53 US and 61 Liberian participants enrolled, totaling 114. However, one Liberian participant was found ineligible post-randomization and did not receive vaccine, so the number who received vaccine is 113. The abstract may refer to randomized participants, while the results refer to enrolled participants.
114 healthy adults (18-50 years of age) were randomized... Of 175 Liberian volunteers screened, 61 (32 female, 29 male) were enrolled... One participant, found ineligible post-randomization, did not receive study vaccine; 60 completed the study.
Abstractreviewer’s wording
Overstated conclusions
None foundConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
Checked — nothing surfaced.
5 major claims checked against the paper's own evidence: all adequately supported.
- supportedReviewers 1, 2The rVSVΔG-LASV-GPC vaccine demonstrated an acceptable safety profile.The paper reports no serious vaccine-related adverse events and no hearing loss, supporting the claim.Evidence: No serious vaccine-related adverse events were reported; no hearing loss was detected.
“No serious vaccine-related adverse events were reported.”
AbstractFind in source - supportedReviewers 1, 2The vaccine was immunogenic over a wide dose range.All doses induced robust antibody and T-cell responses, supporting the claim.Evidence: All doses induced robust long-lasting cellular and humoral responses.
“All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages.”
AbstractFind in source - supportedReviewers 1, 2No infectious vaccine virus particles were found in plasma, urine or saliva.The paper states that no infectious vaccine virus was recovered by plaque assay from RNA-positive samples.Evidence: No infectious vaccine virus was recovered by plaque assay from any RNA-positive samples.
“No infectious vaccine virus was recovered by plaque assay from any RNA-positive samples.”
ResultsFind in source - supportedReviewers 1, 2The vaccine caused dose-dependent, mild-to-severe early-onset systemic reactogenicity that was transient.The paper reports dose-dependent systemic reactogenicity, with Grade 3 events in higher dose groups, resolving within days.Evidence: Eleven (25.6%) US participants, all in Groups 4A and B, reported Grade 3 events... resolving within 1-5 days.
“Eleven (25.6%) US participants, all in Groups 4A and B, reported Grade 3 events.”
ResultsFind in source - supportedReviewer 1Second vaccination provided no appreciable benefit to humoral or cellular responses.The paper states that neutralizing antibodies were not boosted post-second immunization, and T-cell responses appeared similar.Evidence: Like LASV GPC-specific IgG responses, neutralizing antibodies were not boosted post-second immunization (Group 4B).
Like LASV GPC-specific IgG responses, neutralizing antibodies were not boosted post-second immunization (Group 4B).
Resultsreviewer’s wording
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
2 findings · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
- Ethics/consent reporting incompleteAssessed
The introduction cites prior work on Lassa fever outbreaks, the absence of approved vaccines, and the development of rVSVΔG-LASV-GPC, including its 100% efficacy in non-human primates. The rationale for the study is logically linked to the need for a vaccine and the promising preclinical data. The paper does not explicitly discuss limitations of prior research, but the premise is well-established.
“No vaccines are approved for Lassa fever to alleviate health and economic burdens or to prepare for pandemics.”
“This first-in-human study of rVSVΔG-LASV-GPC was designed to assess safety and immunogenicity in healthy US and Liberian adults.”
“No vaccines are approved for Lassa fever to alleviate health and economic burdens or to prepare for pandemics.”
“This first-in-human study of rVSVΔG-LASV-GPC was designed to assess safety and immunogenicity in healthy US and Liberian adults.”
The trial is randomized, double-blind, and placebo-controlled with a 4:1 randomization ratio. Randomization and blinding are described, and the unit of randomization is the participant. Inclusion/exclusion criteria are mentioned but not fully detailed in the main text. The study was not powered for formal hypothesis testing, which is appropriate for a Phase 1 trial. Outlier handling is not explicitly described, but the analysis population is defined.
“This randomized, double-blind, placebo-controlled, dose-escalation, phase 1 study evaluated the safety, tolerability, and immunogenicity of rVSVΔG-LASV-GPC.”
“Healthy participants, aged 18-50 years, from 3 US and 1 Liberian sites were enrolled in eight groups and randomized (4:1) to intramuscular rVSV∆G-LASV-GPC or placebo (matched diluent).”
“This study was not powered for formal hypothesis testing and analyses were not adjusted for multiplicity.”
“This randomized, double-blind, placebo-controlled, dose-escalation, phase 1 study evaluated the safety, tolerability, and immunogenicity of rVSVΔG-LASV-GPC.”
“randomized (4:1) to intramuscular rVSV∆G-LASV-GPC or placebo (matched diluent).”
The paper reports sex (31 female, 22 male in US; 32 female, 29 male in Liberia) and age (median 26 and 24 years). Health status is implied by inclusion criteria (healthy adults). Demographics are summarized in tables. Species/strain and housing conditions are not applicable as this is a human trial.
The paper states 'US FDA and the Liberia Medicine and Health Regulatory Authority Investigational New Drug authorizations, Institutional Review' but does not name a specific IRB or ethics committee. Informed consent is not explicitly described in the main text, though it is implied by the conduct of the trial. Regulatory compliance is mentioned via FDA and Liberian authority authorizations.
“Trial reg: NCT04794218 (https://clinicaltrials.gov/ct2/show/NCT04794218)”
The vaccine candidate rVSVΔG-LASV-GPC is named, and its manufacture is referenced. The ELISA kit (ReLASV® Pan-Lassa NP IgG/IgM ELISA Kit, Zalgen Labs) is identified. Assays for neutralizing antibodies and T-cell responses are described. Software tools are not explicitly identified, but statistical methods are described.
“rVSVΔG-LASV-GPC”
The paper reports geometric means with 95% CIs for antibody responses, which is appropriate. It does not report p-values for primary endpoints, but this is consistent with a descriptive Phase 1 study. The statistical software is not identified. Data presentation includes figures with individual data points and error bars defined as 95% CIs. Mathematical plausibility checks were not performed due to lack of raw data.
“Binding and neutralizing antibody levels were summarized by geometric mean (GM) and 95% confidence interval (CI).”
“This study was not powered for formal hypothesis testing and analyses were not adjusted for multiplicity.”
“This study was not powered for formal hypothesis testing and analyses were not adjusted for multiplicity.”
“Binding and neutralizing antibody levels were summarized by geometric mean (GM) and 95% confidence interval (CI).”
There is no explicit data availability statement in the paper. The trial is registered, but individual patient data are not deposited in a public repository. The paper mentions that the protocol is available at NEJM.org, but this does not constitute a data availability statement. No code sharing is mentioned.
The methods are detailed enough for replication, including dosing, assays, and statistical analysis. The trial is registered (NCT04794218). Limitations are discussed in the Discussion section. Conclusions are proportional to the evidence. Funding sources and conflict of interest are disclosed.
“Trial reg: NCT04794218 (https://clinicaltrials.gov/ct2/show/NCT04794218)”
“Study limitations warrant comment. This was a Phase 1 study and hypothesis testing was not performed.”
“Trial reg: NCT04794218 (https://clinicaltrials.gov/ct2/show/NCT04794218)”
“Study limitations warrant comment. This was a Phase 1 study and hypothesis testing was not performed.”
Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None found · partly checkedReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 38 references by DOI: 37 verified — 1 no DOI (shown, not verified).
- NO DOIEbola vaccination starts in Sierra Leone to prevent new outbreakNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
Copyediting
4 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 4 minor suggestions below.
4 copyedit issues flagged: mostly consistency, clarity, typo.
- MINORconsistencyAbstract“rVSVΔG-LASV-GPC”→ Ensure consistent use of the vaccine name throughout the manuscript.The vaccine name appears with and without the delta symbol in different sections.
- MINORclarityMethods, Trial design and oversight“The assignment into Group 4A occurred for participants declining second dose or to balance the overall group sizes between Group 4A and 4B.”→ Rephrase for clarity: 'Participants who declined a second dose were assigned to Group 4A, or to balance group sizes.'The sentence is awkwardly phrased.
- MINORtypoResults, Vaccine Safety and Reactogenicity“Two (4.2%) Liberian vaccinees reported Grade 3 systemic events, abdominal pain/diarrhea and fever, for 1-2 days.”→ Consider adding a comma after 'events' for clarity.Minor punctuation.
- MINORconsistencyAbstract“rVSVΔG-LASV-GPC”→ Ensure consistent use of the delta symbol (Δ vs ∆) throughout.The delta symbol appears as both Δ and ∆ in the text.
The published work is generally robust, but readers should weigh the missing explicit ethics committee details and informed consent description, and the lack of a data availability statement. The internal contradiction regarding participant counts (114 randomized vs. 113 vaccinated) is minor but should be clarified. No erratum is urgently required, but a data availability statement and ethics details would strengthen transparency.
- 1.HIGHethicsIn the Methods section, explicitly name the institutional review board(s) that approved the study and provide approval numbers.The current text only mentions 'Institutional Review' without specifics, which is a reporting gap for a clinical trial.
- 2.HIGHethicsAdd a statement describing the informed consent process (e.g., written informed consent obtained from all participants) in the Methods.Informed consent is a fundamental ethical requirement and its absence from the main text is a notable omission.
- 3.HIGHdata codeAdd a data availability statement specifying how de-identified data can be accessed (e.g., via a data-sharing agreement or repository like Vivli).The paper currently lacks any data availability statement, which is expected for a data-driven clinical trial.
- 4.MEDIUMreportingIn the Statistical analysis section, identify the statistical software used (e.g., SAS, R) with version numbers.Software identification aids reproducibility and is a standard reporting expectation.
- 5.MEDIUMreportingIn the Methods, describe the randomization method (e.g., computer-generated random sequence) and allocation concealment.The current text states randomization but not the method, which is a common reviewer request.
- 6.MEDIUMreportingDetail the inclusion/exclusion criteria in the main text rather than only referring to the supplement.Full eligibility criteria are important for readers to assess generalizability.
- 7.MEDIUMreportingReference the CONSORT reporting guideline in the Methods or provide a completed CONSORT checklist as supplementary material.Adherence to reporting guidelines improves transparency and completeness.
- 8.MEDIUMstatisticsClarify the discrepancy between the abstract stating 114 participants randomized and the results reporting 113 who received vaccine (one ineligible post-randomization).The internal contradiction could confuse readers and should be explicitly reconciled.
- 9.MEDIUMreportingState how outliers were handled in the statistical analysis, if any, or explicitly state that no outliers were excluded.Outlier handling is a methodological detail that should be transparent.
- 10.LOWcopyeditEnsure consistent use of the vaccine name 'rVSVΔG-LASV-GPC' throughout the manuscript, including the delta symbol (Δ vs ∆).Inconsistent terminology can confuse readers and appears unprofessional.
- 11.LOWcopyeditRephrase the sentence in Methods, Trial design and oversight: 'The assignment into Group 4A occurred for participants declining second dose or to balance the overall group sizes between Group 4A and 4B.' for clarity.The current phrasing is awkward and could be misinterpreted.
- 12.LOWcopyeditAdd a comma after 'events' in the sentence 'Two (4.2%) Liberian vaccinees reported Grade 3 systemic events, abdominal pain/diarrhea and fever, for 1-2 days.'Minor punctuation improves readability.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.