Evaluation of HBs, HBc, and frCP virus-like particles for expression of human papillomavirus 16 E7 oncoprotein epitopes.
OBJECTIVE
In an attempt to develop virus-like particles (VLPs) as experimental vaccine against human papilloma virus (HPV)-induced tumours, the HPV16 E7 oncoprotein epitopes spanning amino acid (aa) residues 35-98 were expressed on three proteins capable of VLP formation: hepatitis B virus (HBV) surface (HBs) and core (HBc) antigens, and RNA phage fr coats (frCP).


METHODS
The profile of immunoglobulin isotypes induced in Balb/C mice after immunization with purified chimeric proteins was studied.


RESULTS
The HBs*-E7(35-54) protein expressing E7 residues 35-54 between residues 139 and 142 of the HBs carrier formed HBs-like particles in Saccharomyces cerevisiae. The HBc Delta-E7(35-98), but not the frCP-E7(35-98), ensured VLP formation in Escherichia coli. In Balb/C mice, the HBs*-E7(35-54) VLPs predominantly induced an anti-E7 antibody, but not anti-HBs carrier response, whereas the HBc Delta-E7(35-98) VLPs induced a lower anti-E7 compared to anti-HBc carrier response. The frCP-E7(35-98) protein elicited equally high antibody responses to both E7 and frCP carrier. Analysis of the immunoglobulin G isotype profile of the antibodies induced by the E7-carrying chimeras showed that the HBs and frCP derivatives were capable of eliciting the Th1 and Th2 subsets of T helper cells, whereas the HBc-derived chimeras elicited only the Th2 subset.


CONCLUSIONS
The HBs and HBc, but not frCP carriers support an efficient outcome for VLPs carrying the HPV16 E7 epitopes. All chimeric proteins may be regarded as potential vaccine candidates.
Pumpens
Paul
P
Biomedical Research and Study Centre, University of Latvia, Riga, Latvia, Lithuania. paul@biomed.lu.lv
Razanskas
Raimundas
R
Pushko
Peter
P
Renhof
Regina
R
Gusars
Indulis
I
Skrastina
Dace
D
Ose
Velta
V
Borisova
Galina
G
Sominskaya
Irina
I
Petrovskis
Ivars
I
Jansons
Juris
J
Sasnauskas
Kestutis
K
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002213:Capsid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D007132:Immunoglobulin Isotypes; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D050725:Papillomavirus E7 Proteins; D012317:RNA Phages / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism
D000914:Antibodies, Viral; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D007132:Immunoglobulin Isotypes; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16