Chimeric hepatitis B core antigen particles containing B- and Th-epitopes of human papillomavirus type 16 E7 protein induce specific antibody and T-helper responses in immunised mice.
The use of hepatitis B core antigen (HBcAg) as an immunogenic delivery vehicle for foreign epitopes has been reported. Here we report the insertion of DNA sequences encoding immunodominant linear B-epitopes and a "universal" T-helper epitope of human papillomavirus (HPV) type 16 E7 transforming protein into the full-length HBcAg gene cloned into an inducible bacterial expression plasmid (pPN1.0). The resulting chimeric proteins assembled into particles which were highly immunogenic. Mice immunised with particles containing one or two of the three E7 B-epitopes under consideration produced strong epitope-specific antibody responses with both IgG and IgG2a components which recognised eukaryotic E7. T-proliferative responses were elicited to the E7 T-epitope as well as HBcAg T-epitope(s). Lymph node cells from immunised mice produced IL-2 and IL-4 when specifically recalled in vitro, indicating stimulation of both Th1 and Th2 helper cell compartments. Since HBcAg particles can be administered in adjuvant acceptable for human application and can elicit mucosal responses after nasal or oral immunisation, these results have implications for vaccine design in HPV 16-associated anogenital cancer.
Tindle
R W
RW
Papillomavirus Research Unit, Lions Human Immunology Laboratory, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Herd
K
K
Londoño
P
P
Fernando
G J
GJ
Chatfield
S N
SN
Malcolm
K
K
Dougan
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000918:Antibody Specificity; D003429:Cross Reactions; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000517:prevention & control; D011993:Recombinant Fusion Proteins / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014412:Tumor Virus Infections / Q000517:prevention & control
D000914:Antibodies, Viral; D016207:Cytokines; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C059731:oncogene protein E7, Human papillomavirus type 16