Segments of puumala hantavirus nucleocapsid protein inserted into chimeric polyomavirus-derived virus-like particles induce a strong immune response in mice.
Insertion of a short-sized epitope at four different sites of yeast-expressed hamster polyomavirus major capsid protein VP1 has been found to result in the formation of chimeric virus-like particles. Here, we demonstrate that the insertion of 45 or 120 amino acid-long segments from the N-terminus of Puumala hantavirus nucleocapsid protein into sites 1 (amino acids 80-89) and 4 (amino acids 288-295) of VP1 allowed the highly efficient formation of virus-like particles. In contrast, expression level and assembly capacity of fusions to sites 2 (amino acids 222-225) and 3 (amino acids 243-247) were drastically reduced. Immunization of BALB/c mice with chimeric virus-like particles induced a high-titered antibody response against the hantavirus nucleocapsid protein, even in the absence of any adjuvant. The strongest response was observed in mice immunized with virus-like particles harboring 120 amino acids of hantavirus nucleocapsid protein. According to the immunoglobulin subclass distribution of nucleocapsid protein-specific antibodies a mixed Th1/Th2 response was detected. The VP1 carrier itself also induced a mixed Th1/Th2 response, which was found to be reduced in mice immunized with virus-like particles harboring 120 amino acid-long inserts. In conclusion, hamster polyomavirus VP1 represents a promising carrier moiety for future vaccine development.
Gedvilaite
Alma
A
Institute of Biotechnology, Vilnius, Lithuania.
Zvirbliene
Aurelija
A
Staniulis
Juozas
J
Sasnauskas
Kestutis
K
Krüger
Detlev H
DH
Ulrich
Rainer
R
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006224:Cricetinae; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology*; D019590:Nucleocapsid Proteins; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D029262:Puumala virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion / Q000276:immunology* / Q000378:metabolism
D000914:Antibodies, Viral; D036022:Capsid Proteins; D019590:Nucleocapsid Proteins; D011993:Recombinant Fusion Proteins; C062481:VP1 protein, polyomavirus; D014765:Viral Vaccines; C100886:nucleocapsid protein, Puumala virus