We conduct basic and applied research to develop products for preventing and treating diseases caused by highly pathogenic hantaviruses, arenaviruses, and orthopoxviruses. Hantaviruses are carried by rodents and cause two disease syndromes in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). We developed a candidate DNA vaccine that protects rodents against the four hantaviruses that cause HFRS. Our hantavirus vaccines have been tested in Phase I and 2a clinical trials (ongoing). We also developed two candidate DNA vaccines against HPS hantaviruses. These vaccines elicit high-titer neutralizing antibodies in rabbits and nonhuman primates and we recently evaluated an Andes virus DNA vaccine in a Phase 1 clinical trial. Passive transfer experiments indicate that sera from these DNA vaccinated monkeys protect hamsters from a lethal HPS hantavirus challenge. The lethal HPS disease model that we discovered (Andes virus causes lethal HPS in Syrian hamsters) is the first lethal disease model for any hantavirus in an adult laboratory animal. This model needs to be more fully characterized and then used to test vaccines, drugs, and immunotherapeutics. In addition, this HPS model can be used to elucidate the mechanisms of hantavirus disease pathogenesis. Our arenavirus work involves developing proof-of-concept DNA vaccines against the South American arenaviruses.

Parallel research efforts focuses on developing a future-generation, gene-based orthopoxvirus vaccine. We have formulated a candidate DNA vaccine comprised of four vaccinia virus genes. This vaccine protects mice (intranasal vaccinia), rabbits (aerosolized rabbitpox), and nonhuman primates (intravenous monkeypox virus) against lethal poxvirus disease. Research opportunities exist to evaluate the immune responses generated by this candidate vaccine and to identify correlates of protective immunity. Our projects involve all aspects of preclinical product development including basic virology, molecular biology, assay development, and animal model development. We work in BSL-2, BSL-3, and BSL-4 (space suite) laboratories.

 

key words

Hantavirus; Hemorrhagic fever with renal syndrome; Hantavirus pulmonary syndrome; Vaccines; DNA vaccines; Immunotherapeutics; Virus; Vaccinia; Orthopoxvirus;

Citizenship:  Open to U.S. citizens, permanent residents and non-U.S. citizens

Level:  Open to Postdoctoral and Senior applicants