Vaccine for Lassa Fever

Overseen By Sarah Litts, MS, BSN, RN

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Wilbur Chen, MD, MS

Must not be taking: Immunosuppressants, Allergy injections

Disqualifiers: Anaphylaxis, Pregnancy, Rabies vaccine, others

Stay on Your Current Meds

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study proposes the evaluation of a novel, first-in-human Lassa fever vaccine based on the complete Lassa glycoprotein complex (GPC) antigen. The antigen will be presented on a genetically modified and attenuated rabies vector expressing both the rabies glycoprotein (GP) antigen and the Lassa GPC. The inactivated chimeric virus is delivered with a toll-like receptor (TLR-4)-activating oil-in-water emulsion adjuvant. Studies using this vaccine administered as a prime-boost series in mice and non-human primates, and then challenged with Lassa virus demonstrated significant protection against Lassa fever. Given that the vaccine backbone is an attenuated and inactivated rabies virus expressing rabies GP, this vaccine will also be evaluated for immunogenicity against rabies virus.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using medications that may impair immune response.

Is the Lassa fever vaccine safe for humans?

The ML29 reassortant vaccine for Lassa fever has shown a good safety profile in non-human primates, with low levels of virus replication and specific immune responses. The LASSARAB vaccine has been tested in animals and shown to be effective, but human safety data is not detailed in the provided research. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for healthy adults aged 18 to 50 who can understand and agree to the study procedures. They must be in good general health without significant medical or psychiatric conditions, and able to attend all study visits.

Inclusion Criteria

I have signed the consent form for this trial.

I understand and agree to follow the study's procedures and attend all visits.

I am between 18 and 50 years old.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the LASSARAB vaccine with aPHAD-SE adjuvant in a dose-escalation study

8 weeks

2 visits (in-person) for vaccinations

Follow-up

Participants are monitored for safety and effectiveness after treatment

56 weeks

Regular follow-up visits

Treatment Details

Interventions

• LASSARAB+ aPHAD-SEat 1400rU (Virus Therapy)

Trial Overview The trial is testing a new Lassa fever vaccine using an altered rabies virus that carries the Lassa glycoprotein complex. It's given with an adjuvant that boosts immune response. The vaccine's effectiveness against both Lassa fever and rabies will be assessed.

Participant Groups

Group I: Cohort 4 - LASSARAB+ aPHAD-SE Vaccine at 1400rU (single) or AC/Placebo Experimental Treatment 3 Interventions

11:3 randomization to investigational vaccine (2 doses) at 14rU or active comparator and normal saline placebo

Group II: Cohort 3 - LASSARAB+ aPHAD-SE Vaccine at 1400rU Single or Double or AC or AC/Placebo Experimental Treatment 3 Interventions

11:2:4:1 randomization to investigational vaccine single dose at 1400rU or investigational vaccine (2 doses) at 14rU or active comparator or active comparator and normal saline placebo

Group III: Cohort 2 - LASSARAB+ aPHAD-SE Vaccine at 700rU or 1400rU or AC Experimental Treatment 3 Interventions

11:4:3 randomization to investigational vaccine dose 700rU or 1400rU or active comparator (n=18)

Group IV: Cohort 1 - LASSARAB+ aPHAD-SE Vaccine at 700rU or Active Comparator (AC) Experimental Treatment 2 Interventions

4:1 randomization to investigational vaccine or active comparator (n=5)

Who Is Running the Clinical Trial?

Wilbur Chen, MD, MS

Lead Sponsor

Trials

1

Recruited

60+

Findings from Research

A single injection of the ML29 reassortant vaccine for Lassa fever was found to induce low levels of virus in the blood and tissues of common marmosets, but it effectively triggered strong immune responses that completely protected them from severe disease.

Gene expression analysis in human immune cells exposed to ML29 confirmed its safety profile, suggesting that ML29 is a promising candidate for further development as a vaccine against Lassa fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates. Lukashevich, IS., Carrion, R., Salvato, MS., et al.[2021]

The LASSARAB vaccine candidate, which combines inactivated Lassa virus and rabies components, successfully generates a strong and lasting immune response in both mice and guinea pigs, providing protection against Lassa fever.

A key mechanism of protection identified is the role of non-neutralizing antibodies targeting the Lassa virus glycoprotein, which enhance immune response through antibody-dependent cellular functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever. Abreu-Mota, T., Hagen, KR., Cooper, K., et al.[2020]

Lassa virus (LASV) causes significant health issues in West Africa, with hundreds of thousands of infections and thousands of deaths each year, highlighting the urgent need for an effective vaccine.

Current vaccine development for Lassa fever is challenged by high costs of animal models and strict biocontainment requirements, necessitating innovative approaches to evaluate vaccine candidates and induce strong immunity against various LASV lineages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The search for animal models for Lassa fever vaccine development. Lukashevich, IS.[2021]

The MV-LASV vaccine candidate demonstrated an acceptable safety profile in a phase 1 trial with 60 healthy adults, showing similar rates of adverse events between the vaccine and placebo groups, with no serious adverse events reported.

The vaccine induced strong immune responses, with significant levels of LASV-specific IgG antibodies observed, indicating its potential effectiveness in providing immunity against Lassa fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial. Tschismarov, R., Van Damme, P., Germain, C., et al.[2023]

Four Lassa fever vaccine candidates have reached clinical trials, with five phase 1 trials and one phase 2 trial registered, indicating progress in vaccine development.

Current trials primarily focus on healthy adults, with one trial including a broader age range, suggesting a cautious approach to assessing safety and efficacy in diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lassa fever vaccine candidates: A scoping review of vaccine clinical trials. Sulis, G., Peebles, A., Basta, NE.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever. [2020]

3. England pubmed.ncbi.nlm.nih.gov

The search for animal models for Lassa fever vaccine development. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Immunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Lassa fever vaccine candidates: A scoping review of vaccine clinical trials. [2023]