A Phase 1 clinical trial has demonstrated the safety and immunogenicity of DNA vaccines targeting Hantaan (HTNV) and Puumala (PUUV) viruses, two major causes of hemorrhagic fever with renal syndrome (HFRS). The study, published in Nature, utilized a needle-free injection system (PharmaJet Stratis) to deliver the vaccines, offering a potentially more accessible and patient-friendly administration route. The research was conducted by scientists at the Walter Reed Army Institute of Research.
The trial enrolled 27 healthy adult volunteers who were randomized into three groups: one receiving the HTNV DNA vaccine, another receiving the PUUV DNA vaccine, and a third receiving a combination of both. Participants received up to four vaccinations on days 0, 28, 56, and optionally on day 168. The primary outcome was the assessment of safety and tolerability, while secondary outcomes included the evaluation of immunogenicity through the measurement of neutralizing antibody responses.
Safety and Tolerability
The DNA vaccines were found to be safe and well-tolerated. Solicited adverse events (AEs) were mostly mild (Grade 1), including injection site reactions such as redness, swelling, and pain, as well as systemic symptoms like myalgias, fatigue, and headache. No serious adverse events (SAEs) related to the vaccine were reported. Laboratory assessments, including hematology and serum chemistry tests, did not reveal any clinically significant abnormalities.
Immunogenicity
Immunogenicity was assessed using pseudovirion neutralization assays (PsVNA) and plaque reduction neutralization tests (PRNT). The results showed that the vaccines induced neutralizing antibody responses against both HTNV and PUUV in some participants. Peak geometric mean titers were determined for specified timepoints, and seropositivity rates were analyzed. The proportion of seropositive subjects (PsVNA50 and/or PRNT50 ≥ 20) was a primary analysis variable. While the antibody responses were not universally observed across all participants, the study demonstrated the potential of the DNA vaccine approach to elicit immunity against hantaviruses.
Vaccine Design and Administration
The HTNV DNA vaccine plasmid, pWRG/HTN-M (co), and the PUUV DNA vaccine plasmid, pWRG/PUU-M(s2), were produced under current good manufacturing practices (cGMP) by Althea Technologies, Inc. The vaccines were administered using the PharmaJet Stratis device, which delivers a 0.5 mL jet of liquid at high pressure, penetrating the skin into the muscle. This needle-free system has been previously used for the delivery of other DNA vaccines, including an Andes virus DNA vaccine.
Implications and Future Directions
HFRS is a significant public health concern in many parts of the world, particularly in Asia and Europe. These diseases are caused by hantaviruses, which are transmitted to humans through contact with infected rodents. Currently, there are limited treatment options available, and prevention relies primarily on rodent control measures. The development of effective vaccines is therefore a high priority.
This Phase 1 trial provides encouraging evidence for the safety and immunogenicity of DNA vaccines against HTNV and PUUV. The needle-free delivery system offers advantages in terms of ease of administration and patient acceptability. Further studies are needed to optimize the vaccine design, improve immunogenicity, and evaluate the efficacy of these vaccines in preventing HFRS in at-risk populations.
