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.
Lassa fever is a zoonotic infection endemic in West Africa and is spread by the Lassa virus, an arenavirus causing hemorrhagic fever. Up to 300,000 Lassa fever infections occur annually and while disease is often mild, in a subset of individuals disease is characterized by severe anemia, bleeding, encephalopathy, respiratory failure, shock, and high mortality. In some regions of West Africa, up to 15% of hospital admissions are secondary to Lassa fever, and an estimated 5,000 deaths occur annually. During epidemics of disease, case-fatality rates may reach as high as 50% in hospitalized patients. Approximately one-third of infected individuals will develop hearing loss regardless of disease severity, and in a proportion of patients, permanent deafness occurs. Prevention of illness through vaccination is a critical goal in reducing the burden of disease from Lassa fever. There are currently no vaccines or therapeutics demonstrated to be efficacious in the prevention or treatment of Lassa fever. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
55
Rabies-Vectored Monovalent Lassa Fever Vaccine (LASSARAB) with 3D-(6- acyl) Phosphorylated Hexaacyl Disaccharides (PHAD)-Stable squalene oil-in-water nanoemulsion (aPHAD-SE) adjuvant administered by IM injection
Sterile, stable, freeze-dried suspension of rabies virus prepared from strain PM-1503-3M
Sterile 0.9% sodium chloride for injection, USP, or normal saline, is a sterile, nonpyrogenic, isotonic solution; each mL contains sodium chloride 9 mg
Rabies-Vectored Monovalent Lassa Fever Vaccine (LASSARAB) with 3D-(6- acyl) Phosphorylated Hexaacyl Disaccharides (PHAD)-Stable squalene oil-in-water nanoemulsion (aPHAD-SE) adjuvant administered by IM injection
University of Maryland, Baltimore, University of Maryland School of Medicine, Center for Vaccine Development and Global Health
Baltimore, Maryland, United States
Number of participants experiencing solicited local and systemic events
Number of participants experiencing solicited local and systemic reactogenicity Adverse Events (AEs)
Time frame: From Day 1 through Day 8 for the first vaccination and from Day 29 through Day 36 for the second vaccination, as applicable
Percentage of participants experiencing solicited local and systemic events
Percentage of participants experiencing solicited local and systemic reactogenicity Adverse Events (AEs)
Time frame: From Day 1 through Day 8 for the first vaccination and from Day 29 through Day 36 for the second vaccination, as applicable
Number of participants experiencing unsolicited events
Number of participants experiencing any unsolicited AEs
Time frame: Day 1 through Day 61
Percentage of participants experiencing unsolicited events
Percentage of participants experiencing any unsolicited AEs
Time frame: Day 1 through Day 61
Number of participants experiencing Serious Adverse Events (SAEs)
Number of participants experiencing SAEs
Time frame: Day 1 through Day 394
Percentage of participants experiencing Serious Adverse Events (SAEs)
Percentage of participants experiencing SAEs
Time frame: Day 1 through Day 394
Number of participants experiencing Medically-Attended Adverse Events (MAAEs)
Number of participants experiencing MAAEs
Time frame: Day 1 through Day 394
Percentage of participants experiencing Medically-Attended Adverse Events (MAAEs)
Percentage of participants experiencing MAAEs
Time frame: Day 1 through Day 394
Number of participants experiencing New-Onset Chronic Medical Conditions (NOCMCs)
Number of participants experiencing NOCMCs
Time frame: Day 1 through Day 394
Percentage of participants experiencing New-Onset Chronic Medical Conditions (NOCMCs)
Percentage of participants experiencing NOCMCs
Time frame: Day 1 through Day 394
Number of participants experiencing Potential Immune-Mediated Medical Conditions (PIMMCs)
Number of participants experiencing PIMMCs
Time frame: Day 1 through Day 394
Percentage of participants experiencing Potential Immune-Mediated Medical Conditions (PIMMCs)
Percentage of participants experiencing PIMMCs
Time frame: Day 1 through Day 394
Number of participants experiencing Adverse Event of Special Interest (AESI)
Number of participants experiencing Adverse Event of Special Interest (AESI) - new onset sensorineural hearing loss (SNHL)
Time frame: Day 1 through Day 394
Percentage of participants experiencing Adverse Event of Special Interest (AESI)
Percentage of participants experiencing Adverse Event of Special Interest (AESI) - new onset sensorineural hearing loss (SNHL)
Time frame: Day 1 through Day 394
Number of participants experiencing clinical laboratory AEs
Number of participants experiencing clinical laboratory AEs
Time frame: Day 1 through Day 61
Percentage of participants experiencing clinical laboratory AEs
Percentage of participants experiencing clinical laboratory AEs
Time frame: Day 1 through Day 61
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