Subject(s)
Hepatitis B Surface Antigens/immunology , Hepatitis B Vaccines/history , Hepatitis B virus/immunology , Vaccines, Inactivated/history , Animals , Callithrix , Guinea Pigs , Hepatitis B/history , Hepatitis B/prevention & control , Hepatitis B Vaccines/immunology , History, 20th Century , Pan troglodytes , Vaccines, Inactivated/immunologyABSTRACT
A soluble complex of poly I:C and poly-L-lysine (poly I:C/poly-L-lysine) has been prepared that induces high titers of circulating interferon in monkeys. By limiting the molar ratio of lysine to nucleotide to 0.5, a complex was formed that was soluble up to 2.0 mg poly I:C/ml of phosphate-buffered saline. Complexes of poly I:C with poly-L-lysine of various molecular weights, and in a constant ratio (0.5) of lysine to nucleotide, were evaluated for capacity to induce serum interferon in grivet monkeys. Substantial enhancement (10- to 100-fold) of the capacity of poly I:C to induce interferon in grivet monkeys was observed using poly I:C complexed with poly-L-lysines of molecular weight 10(4) daltons or greater. The poly I:C/poly-L-lysine as an effective inducer of interferon in grivet monkeys, rhesus monkeys, chimpanzees and marmosets. A high interferon titer (greater than 100 units/ml blood) was maintained in grivet monkeys by repeated daily administration of the complex. No long-term hyporesponsiveness was noted following repeat inductions over a period of months. The serum interferon produced in monkeys in response to poly I:C/poly-L-lysine resembled human leukocyte interferon in its biological characteristics.
Subject(s)
Interferon Inducers/administration & dosage , Peptides/administration & dosage , Poly I-C/administration & dosage , Polylysine/administration & dosage , Animals , Chlorocebus aethiops , Drug Combinations , Molecular Weight , SolubilityABSTRACT
A highly purified and inactivated vaccine was made of hepatitis B virus surface antigen. The vaccine was tested exhaustively for safety by ordinary procedures and additionally in chimpanzees and marmosets. It was highly potent and induced antibody in guinea pigs, grivet monkeys, and chimpanzees after three doses of vaccine were given subcutaneously. Chimpanzees given three doses of vaccine were protected against challenge with 1,000 chimpanzee-infectious doses of live human hepatitis B virus given intravenously in controlled studies. Tests of the vaccine for control of hepatitis B in man are to be carried out.
Subject(s)
Hepatitis B virus/immunology , Hepatitis B/prevention & control , Viral Vaccines , Animals , Antibodies, Viral/analysis , Callitrichinae/immunology , Evaluation Studies as Topic , Guinea Pigs , Haplorhini , Humans , Injections, Subcutaneous , Pan troglodytes/immunology , Viral Vaccines/administration & dosageABSTRACT
Highly purified hepatitis B virus surface antigen (Australia antigen) purified by physical and chemical procedures from infected human plasma was used to prepare hepatitis B vaccine. The purified antigen was treated with formalin and the vaccine was tested exhaustively for safety by ordinary procedures and additionally in marmosets (for live hepatitis B virus). The vaccine was highly potent, inducing antibody in guinea pigs, grivet monkeys, and chimpanzees given three doses of vaccine containing up to 20 mug of hepatitis B antigen per dose. A protective efficacy trial was carried out in chimpanzees that were given three doses of vaccine subcutaneously and then challenged intravenously with 1000 chimpanzee infectious doses of human hepatitis B virus. All of five unvaccinated control animals developed hepatitis B virus antigenemia following challenge and all of six vaccinated animals were protected, including one animal that had failed to develop detectable antibody following vaccination.
Subject(s)
Hepatitis B Antigens , Hepatitis B/prevention & control , Vaccines , Animals , Antibodies, Viral/biosynthesis , Guinea Pigs , Haplorhini , Hepatitis B/immunology , Hepatitis B Antibodies/biosynthesis , Hepatitis B virus/immunology , Pan troglodytesABSTRACT
Developments leading to the preparation and testing for safety and potency of a highly purified inactivated preparation of hepatitis B surface antigen are descirbed. Protective efficacy studies in chimps of a lot of the inactivated hepatitis B vaccine are currently and suitable for clinical trials in man.
Subject(s)
Hepatitis B Surface Antigens , Viral Vaccines , Animals , Antibody Formation , Haplorhini , Hepatitis B Antibodies , Humans , Pan troglodytes , Vaccines, AttenuatedSubject(s)
Poly I-C , Animals , Antibodies/analysis , Antigens , Biological Assay , Chromatography, Gel , Cytosine Nucleotides/analysis , Injections, Intraperitoneal , Injections, Intravenous , Interferon Inducers , Mice , Molecular Weight , Poly I-C/administration & dosage , Poly I-C/analysis , Poly I-C/chemical synthesis , Poly I-C/toxicity , Polynucleotides/analysis , Rabbits , Ribonucleases/metabolismSubject(s)
Interferon Inducers/analysis , Newcastle disease virus/analysis , RNA, Viral/isolation & purification , Semliki forest virus/analysis , Sindbis Virus/analysis , Animals , Antiviral Agents/analysis , Cells, Cultured , Chick Embryo , Complement Fixation Tests , Immune Sera , Kidney , Nucleic Acid Denaturation , Poly I-C , Rabbits/immunology , RibonucleasesSubject(s)
Cells, Cultured/metabolism , Interferons/biosynthesis , Polynucleotides/pharmacology , Animals , Carbon Isotopes , Cell Fractionation , Cell-Free System , Cells, Cultured/drug effects , Centrifugation, Density Gradient , Cycloheximide/pharmacology , Cytosine Nucleotides/metabolism , Inosine Nucleotides/metabolism , Kidney , Nucleosides/metabolism , Poly I-C/pharmacology , Polynucleotides/metabolism , Puromycin/pharmacology , Rabbits , Temperature , Time Factors , Tritium , Trypsin , Vesicular stomatitis Indiana virusSubject(s)
Interferons/biosynthesis , Polynucleotides , Virus Diseases/prevention & control , Administration, Oral , Animals , Antibody Formation , Humans , Injections, Intravenous , Interferons/pharmacology , Interferons/therapeutic use , Mice , Neoplasms/drug therapy , Neoplasms, Experimental/drug therapy , Poly I-C/administration & dosage , Poly I-C/pharmacology , Rabbits , Rhinovirus/drug effects , Simplexvirus/drug effects , Time Factors , Vaccinia virus/drug effectsSubject(s)
Interferons/biosynthesis , Polynucleotides/pharmacology , Adolescent , Adult , Aged , Breast Neoplasms/drug therapy , Clinical Trials as Topic , Complement Fixation Tests , DNA , Female , Hodgkin Disease/drug therapy , Hot Temperature , Humans , Interferons/blood , Laryngeal Neoplasms/drug therapy , Leukemia/drug therapy , Leukemia, Monocytic, Acute/drug therapy , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Melanoma/drug therapy , Mesothelioma/drug therapy , Middle Aged , Nasopharyngeal Neoplasms/drug therapy , Nucleic Acid Denaturation , Poly I-C/pharmacology , Teratoma/drug therapy , Testicular Neoplasms/drug therapy , Urinary Bladder Neoplasms/drug therapy , Uterine Cervical Neoplasms/drug therapySubject(s)
Interferons/biosynthesis , Molecular Weight , Pneumonia, Viral/immunology , Polynucleotides , Vesicular stomatitis Indiana virus/immunology , Animals , Chemical Phenomena , Chemistry , Chromatography , Culture Techniques , Cytosine Nucleotides , Mice , Nucleosides , Optics and Photonics , Rabbits , Ribonucleases/pharmacology , Ultrasonics , ViscosityABSTRACT
A discussion of factors considered influential in making a polynucleotide an efficient inducer of interferon was presented. These factors were double-strandedness of the polynucleotides, the sugar moiety of the polynucleotides, thermal stability, resistance to enzymatic degradation, and molecular size of the polynucloetides. Recent developments concerning interferon induction during virus infection were also discussed.