ABSTRACT
Chimeric HBcAg proteins carrying epitopes from surface hepatitis B virus (HBV) protein (regions 137-147 a.o. HBsAg, 27-37 a.a. region preS1 and 131-145 a.a. region preS2) have been early constructed. This paper presents the data of an investigation of a humoral immune response in mice immunized with obtained by chimeric HBcAg proteins. The findings suggest that the chimeric HBcAg proteins carrying the epitopes of surface HBV protein are able to induce an immune response to both inserted epitopes and carrying protein (HBcAg). Immunization with a mixture of chimeric proteins taken in equivalent quantities induces the synthesis of antibodies to hybrid proteins. The use of aluminum hydroxide considerably enhances a humoral immune response during immunization with chimeric bovine proteins.
Subject(s)
Epitopes/immunology , Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/immunology , Hepatitis B/immunology , Immunization , Adjuvants, Immunologic/administration & dosage , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/immunology , Animals , Epitopes/administration & dosage , Epitopes/genetics , Hepatitis B/blood , Hepatitis B Core Antigens/administration & dosage , Hepatitis B Core Antigens/genetics , Hepatitis B Surface Antigens/administration & dosage , Hepatitis B Surface Antigens/genetics , Immunization Schedule , Injections, Intramuscular , Mice , Mice, Inbred BALB C , Recombinant Proteins/administration & dosage , Recombinant Proteins/immunology , Vaccines, Synthetic/immunologyABSTRACT
The hepatitis B core antigen (HBcAg) was used to present the HIV epitopes and mimics selected by phage display. The HIV epitopes were inserted into the el loop of HBcAg. The influence of insertions on the ability of chimeric HBcAg to assemble itself was studied. Special soft was made use of to detect the regularities between certain physical-and-chemical properties of amine-acid residua (belonging to an inserted alien peptide) and the presence or loss of the ability of HBcAg to assemble itself. Recommendations are provided of how to overcome difficulties related with the presentation of alien epitopes.
Subject(s)
Epitopes/immunology , HIV-1/immunology , HIV-2/immunology , Hepatitis B Core Antigens/chemistry , Hepatitis B Core Antigens/immunology , Recombinant Fusion Proteins/biosynthesis , Amino Acid Sequence , Antibodies, Viral/biosynthesis , Drug Delivery Systems , HIV Infections/immunology , HIV Infections/prevention & control , HIV Infections/virology , Hepatitis B Core Antigens/metabolism , Humans , Protein Folding , Protein Structure, Secondary , Protein Structure, Tertiary , Recombinant Fusion Proteins/chemistry , Recombinant Fusion Proteins/metabolism , Sequence Analysis, Protein , Vaccines, Synthetic , Viral VaccinesABSTRACT
A recombinant strain producing TBI protein (artificial protein containing HIV-1 B and T cell epitopes) was constructed on the base of attenuated Salmonella typhimurium SL7207 strain and BALB/c mice were immunized with this strain in a dose of 10(9) live cells orally or rectally. A single immunization with the recombinant salmonella strain induced humoral and cellular immune response to HIV-1; hence, this strain is a promising candidate for vaccine against HIV.
Subject(s)
AIDS Vaccines/immunology , Genes, Synthetic , HIV-1/immunology , Proteins/immunology , Salmonella typhimurium/immunology , AIDS Vaccines/administration & dosage , AIDS Vaccines/biosynthesis , Administration, Oral , Administration, Rectal , Animals , Antibodies, Viral/analysis , Antibody Formation , HIV Infections/immunology , HIV Infections/prevention & control , Immunity, Cellular , Immunoenzyme Techniques , Mice , Mice, Inbred BALB C , Protein Biosynthesis , Proteins/genetics , Recombinant Proteins/biosynthesis , Recombination, Genetic , Salmonella typhimurium/genetics , Spleen/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/biosynthesis , Vaccines, Synthetic/immunologyABSTRACT
In this work the results of obtaining HBcAg-producing attenuated Salmonella strains, serovars S. enteritidis and S. typhimurium, and their comparative study is presented. As revealed in this study, attenuated S. enteritidis strain E-23 and S. typhimurium strain T-10, producing HBcAg, induce cell-mediated and humoral immune response to HBcAg after injected into anovals. After injection S. typhimurium strain T-10 induces a much higher titer of specific antibodies than S. enteritidis strain E-23. The level of specific antibodies induced by recombinant HBcAg seems to correlate with the capacity of salmonellae for survival inside macroorganisms.
Subject(s)
Antigen Presentation , Hepatitis B Core Antigens/immunology , Salmonella enteritidis/immunology , Salmonella typhimurium/immunology , Animals , Genetic Vectors/immunology , Hepatitis B/immunology , Hepatitis B/prevention & control , Hepatitis B Core Antigens/genetics , Hepatitis B Vaccines/genetics , Hepatitis B Vaccines/immunology , Immunity, Mucosal , Mice , Mice, Inbred BALB C , Plasmids/genetics , Recombination, Genetic , Salmonella enteritidis/genetics , Salmonella typhimurium/genetics , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunologyABSTRACT
Hepatitis B core antigen is one of the most promising protein carriers of foreign epitopes of various human and animal pathogens. Chimeric HBcAg particles can be used as effective artificial immunogenes. Unfortunately, not all chimeric proteins are able to be particulated. The dependence of correct or incorrect folding of chimeric proteins on physical and chemical properties of inserts was studied with the help of ProAnalyst, SALIX and QSARPro computer programs. We have found that insertion of amino acids with high hydrophobicity, large volume, and high beta-strand index prevent self-assembling chimeric proteins. These factors are most important for the C-termini of inserts. Recommendations for obtaining correct folding of chimeric HBcAg particles have been given.
