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Construction and nonclinical testing of a Puumala virus synthetic M gene-based DNA vaccine
R L Brocato1, M J Josleyn, V Wahl-Jensen
1Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
Abstract:
Puumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-length M segment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model.
Insights
A novel DNA vaccine targeting Puumala virus (PUUV) successfully generated neutralizing antibodies and protected hamsters from PUUV infection. Unexpectedly, it also protected against a lethal Andes virus (ANDV) model without cross-neutralizing antibodies.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Puumala virus (PUUV) causes hemorrhagic fever with renal syndrome (HFRS), a disease with significant socioeconomic impact but no licensed vaccine or specific treatment.
- Current HFRS treatments are supportive, highlighting the need for effective preventive strategies against PUUV and related hantaviruses.
Purpose of the Study:
- To synthesize and characterize a DNA vaccine targeting the M segment of PUUV.
- To evaluate the immunogenicity and protective efficacy of the developed DNA vaccine in animal models.
Main Methods:
- A codon-optimized, full-length M segment open reading frame of PUUV was synthesized and cloned into a DNA vaccine vector (pWRG/PUU-M(s2)).
- The plasmid was delivered via gene gun to hamsters and nonhuman primates to assess antibody production.
- Vaccinated hamsters were challenged with PUUV and related hantaviruses, including Andes virus (ANDV), to evaluate protection.
Main Results:
- The DNA vaccine plasmid pWRG/PUU-M(s2) successfully induced high-titer neutralizing antibodies in both hamsters and nonhuman primates.
- Vaccination conferred protection against PUUV infection in hamsters.
- Remarkably, vaccination also protected hamsters against a lethal ANDV challenge, despite the absence of detectable ANDV cross-neutralizing antibodies.
Conclusions:
- The experimental DNA vaccine is immunogenic and provides protection against homologous PUUV infection.
- The vaccine demonstrates cross-protection against a lethal hantavirus disease model (ANDV), suggesting a potential broader application for hantavirus prevention.
- This study presents the first evidence of a DNA vaccine for HFRS offering protection in a lethal hantavirus disease model.
