T cell-independent type I antibody response against B cell epitopes expressed repetitively on recombinant virus particles.
Recombinant viral or virus-like particles offer new tools for vaccine development. This study investigated hepatitis B core antigen (HBcAg) capsids and RNA phage Qbeta coats as carriers of a foreign epitope to induce antibody responses in mice. HBcAg capsids were shown to induce T cell-independent (TI) antibodies. We found that these particles behave as antigen-specific TI type 1 (TI-1) Ag comparable to other rigidly structured viruses. When a 5-aa long epitope of the pre-S1 domain of hepatitis B surface antigen (HBsAg) was introduced into the optimal position of the HBc molecule, it also behaved as a TI-1 Ag. Best efficiency of the antibody response to the foreign epitope was achieved by a compensatory deletion after the epitope to retain the regular structure of the HBcAg capsid with a highly repetitive superficial exposition of the foreign epitope. For recombinant Qbeta phage coats, a much more efficient antibody response to the foreign epitope was achieved when the foreign epitope was expressed repetitively on a particulate derivate of Qbeta phage coats. Thus, recombinant virus particles are suitable vaccine carriers for the introduction of foreign B cell epitopes, if precise structural requirements are fulfilled.
Fehr
T
T
Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
Skrastina
D
D
Pumpens
P
P
Zinkernagel
R M
RM
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000737:chemistry / Q000276:immunology; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology; D011995:Recombination, Genetic; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D006514:Hepatitis B Surface Antigens; D016056:Immunodominant Epitopes; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen