Hantaan/Andes virus DNA vaccine elicits a broadly cross-reactive neutralizing antibody response in nonhuman primates.
At least four hantavirus species cause disease with prominent renal involvement-hemorrhagic fever with renal syndrome (HFRS); and several hantavirus strains cause disease with significant pulmonary involvement-hantavirus pulmonary syndrome (HPS). The most prevalent and lethal hantaviruses associated with HFRS and HPS are Hantaan virus (HTNV) and Andes virus (ANDV), respectively. Here, we constructed a DNA vaccine plasmid (pWRG/HA-M) that contains both the HTNV and ANDV M gene segments. Rhesus macaques vaccinated with pWRG/HA-M produced antibodies that bound the M gene products (i.e., G1 and G2 glycoproteins), and neutralized both HTNV and ANDV. Neutralizing antibody titers elicited by the dual-immunogen pWRG/HA-M, or single-immunogen plasmids expressing only the HTNV or ANDV glycoproteins, increased rapidly to high levels after a booster vaccination administered 1-2 years after the initial vaccination series. Memory responses elicited by this long-range boost exhibited an increased breadth of cross-neutralizing activity relative to the primary response. This is the first time that hantavirus M gene-based DNA vaccines have been shown to elicit a potent memory response, and to elicit antibody responses that neutralize viruses that cause both HFRS and HPS.
Hooper
Jay W
JW
Department of Molecular Virology, Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA. Jay.Hooper@amedd.army.mil
Custer
David M
DM
Smith
Jeffrey
J
Wahl-Jensen
Victoria
V
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D006224:Cricetinae; D003429:Cross Reactions; D018063:Hantaan virus / Q000235:genetics* / Q000276:immunology*; D006476:Orthohantavirus / Q000235:genetics* / Q000276:immunology*; D007117:Immunization, Secondary; D008253:Macaca mulatta; D009500:Neutralization Tests; D013045:Species Specificity; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014763:Viral Matrix Proteins; D014765:Viral Vaccines