ABSTRACT
Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immuno adjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system.
Subject(s)
Adjuvants, Immunologic/chemistry , Organophosphorus Compounds/immunology , Vaccination/methods , Adjuvants, Immunologic/administration & dosage , Animals , Aziridines/chemistry , Aziridines/immunology , Injections, Intradermal , Molecular Structure , Organophosphorus Compounds/chemistry , Polymers/chemistry , Sus scrofaABSTRACT
Ross River virus is a mosquito-borne alphavirus which causes several thousand cases of arthritis (epidemic polyarthritis) each year. In this study, binary ethylenimine (BEI) was used to destroy the infectivity of this virus without abolishing the antigenicity or immunogenicity of the virion. Mice immunized intramuscularly with BEI-inactivated virus, with or without Alhydrogel adjuvant, produced antibody which neutralized Ross River virus in vitro, and the mice also failed to develop viraemia when challenged intravenously with live virus. Serum neutralization and in vivo protection were greatest when BEI-inactivated virus was administered without adjuvant.
Subject(s)
Alphavirus Infections/virology , Arthritis, Infectious/virology , Ross River virus/immunology , Viral Vaccines , Adjuvants, Immunologic , Alphavirus Infections/prevention & control , Animals , Antibodies, Viral/biosynthesis , Arthritis, Infectious/prevention & control , Aziridines/immunology , Aziridines/pharmacology , Chlorocebus aethiops , Enzyme-Linked Immunosorbent Assay , Humans , Immune Sera/immunology , Immunization, Secondary , Injections, Intramuscular , Mice , Mice, Inbred BALB C , Muscle, Skeletal/pathology , Neutralization Tests , Ross River virus/drug effects , Ross River virus/genetics , Vaccination , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/immunology , Vero Cells , Viral Vaccines/administration & dosage , Viral Vaccines/immunologyABSTRACT
Se estudiaron cuatros operarios sobre un total de diez afectados, que trabajaban en una empresa de productos farmacéuticos para veterinaria que manipulaban etilenimina para la elaboración de vacuna antiaftosa. El objeto del presente trabajo fue determinar si la E. es el agente causal en diez operarios afectados por dermitis por contacto alérgica en una industria que la emplea y, en caso de confirmar esta participación, indicar las medidas de profilaxis respectiva
Subject(s)
Dermatitis, Contact/chemically induced , Aziridines/adverse effects , Dermatitis, Contact/immunology , Dermatitis, Contact/etiology , Aziridines/immunology , Aziridines/metabolism , Dermatitis, Occupational/prevention & control , Skin Tests , Aphthovirus/drug effects , Viral VaccinesABSTRACT
Se estudiaron cuatros operarios sobre un total de diez afectados, que trabajaban en una empresa de productos farmacéuticos para veterinaria que manipulaban etilenimina para la elaboración de vacuna antiaftosa. El objeto del presente trabajo fue determinar si la E. es el agente causal en diez operarios afectados por dermitis por contacto alérgica en una industria que la emplea y, en caso de confirmar esta participación, indicar las medidas de profilaxis respectiva
Subject(s)
Aziridines/adverse effects , Dermatitis, Contact/chemically induced , Aphthovirus/drug effects , Aziridines/immunology , Aziridines/metabolism , Dermatitis, Contact/etiology , Dermatitis, Contact/immunology , Dermatitis, Occupational/prevention & control , Skin Tests , Viral VaccinesABSTRACT
The effects of BM 12 531, a 2-cyanaziridinyl derivative, on in vitro generation of Con A induced suppressor cells as well as generation of spontaneous suppressor cells in peripheral blood lymphocytes of 9 chronic myeloid leukemia (CML) patients in remission, 9 patients with active Hodgkin's disease (HD) and 12 normal healthy donors were studied. The suppressor cells generated spontaneously and with Con A, in the presence and absence of the drug, were tested for their modulating effect on mitogenic (PHA) response of autologous lymphocytes. The results indicate that the addition of the drug at the time of generation of suppressor cells decreased the spontaneous suppressor cell activity in 2/4 healthy donors, 3/7 CML patients and 4/6 HD patients. Con A induced suppressor cell activity generated in presence of the drug was significantly reduced in 7/12 healthy donors, 6/9 CML patients and 3/9 HD patients.
Subject(s)
Aziridines/pharmacology , Azirines/pharmacology , Concanavalin A/immunology , Hodgkin Disease/immunology , Leukemia, Myeloid/immunology , T-Lymphocytes, Regulatory/drug effects , Aziridines/immunology , Cells, Cultured , Humans , Lymphocyte Activation , T-Lymphocytes, Regulatory/immunologySubject(s)
Adjuvants, Immunologic/immunology , Immunization , T-Lymphocytes/immunology , Animals , Aziridines/immunology , Ditiocarb/immunology , Humans , Inosine Pranobex/immunology , Levamisole/immunology , Mice , Mycobacterium bovis/immunology , Peptides/immunology , Polysaccharides/immunology , Propionibacteriaceae/immunology , Rabbits , Toxoids/immunology , Vaccines/immunologyABSTRACT
Formalin, glycidaldehyde, and the binary ethyleneimine were tested under laboratory conditions as inactivators of the foot-and-mouth disease virus along with the possibility of using them in the process of vaccine production. Data is presented on the comparative testing for innocuity and immunogenicity for sheep of F. M. D. vaccines produced with such inactivators. Results showed the advantages of the binary ethyleneimine as against formalin and glycidaldehyde as an inactivator of the F. M. D. virus.
Subject(s)
Antiviral Agents/immunology , Aphthovirus/immunology , Viral Vaccines/immunology , Aldehydes/immunology , Animals , Antibodies, Viral/analysis , Aziridines/immunology , Clinical Trials as Topic/veterinary , Epoxy Compounds/immunology , Formaldehyde/immunology , Quality Control , Sheep , Time Factors , Vaccines, Attenuated/immunologySubject(s)
Aziridines/pharmacology , Azirines/pharmacology , Rosette Formation , T-Lymphocytes/immunology , Aziridines/immunology , Hodgkin Disease/immunology , Humans , In Vitro Techniques , Leukocyte Migration-Inhibitory Factors/biosynthesis , Multiple Myeloma/immunology , T-Lymphocytes/drug effectsABSTRACT
The effect of BM 12.531 (BM) treatment on normal or tumored mice was studied under both in vitro and in vivo experimental conditions. It was found that BM treatment of mice that received 500 R of whole body irradiation caused a highly significant (P < 0.001) increase in the prolongation of the mean survival time. BM was found to significantly increase (P < 0.01) the delayed-type hypersensitivity reaction of normal mice. BM treatment was found to moderately increase both in vivo and in vitro activated macrophages. However, BM was found to be extremely effective in significantly increasing the mean survival times of lung carcinoma-bearing or leukemic mice.
Subject(s)
Aziridines/pharmacology , Azirines/pharmacology , Immunity, Cellular/drug effects , Neoplasms, Experimental/drug therapy , Animals , Ascitic Fluid/cytology , Aziridines/immunology , Cells, Cultured , Hypersensitivity, Delayed/chemically induced , Leukemia L1210/drug therapy , Leukemia, Experimental/drug therapy , Lung Neoplasms/drug therapy , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred BALB C , X-RaysABSTRACT
BM 12.531, 2-[2-cyranaziridinyl-(1)]-2-[2-carbamoylaziridinyl-(1)]-propane, a new immunostimulant compound, increased the resistance of mice to infection with Candida albicans. Because BM 12.531 had no fungistatic activity in vitro, it is proposed that the therapeutic effect of BM 12.531 is caused by the stimulation of cell-mediated immunity. Administration of cyclophosphamide alone increased the mortality among mice infected with C. albicans and Pseudomonas aeruginosa, but when BM 12.531 was then administered to these animals, the mortality was reduced. Among mice with acute Escherichia coli infection, a synergistic effect of chloramphenicol and BM 12.531 was demonstrated.
Subject(s)
Aziridines/immunology , Azirines/immunology , Immunity, Cellular/drug effects , Animals , Candidiasis/immunology , Chloramphenicol/therapeutic use , Cyclophosphamide/therapeutic use , Drug Evaluation, Preclinical , Drug Synergism , Drug Therapy, Combination , Escherichia coli Infections/immunology , Female , In Vitro Techniques , Mice , Mice, Inbred Strains , Microbial Sensitivity Tests , Pseudomonas Infections/immunology , Stimulation, ChemicalSubject(s)
Adjuvants, Immunologic/pharmacology , Antineoplastic Agents/administration & dosage , Pseudomonas aeruginosa/immunology , Animals , Anti-Bacterial Agents/immunology , Antineoplastic Agents/adverse effects , Aziridines/immunology , BCG Vaccine/therapeutic use , Bacterial Vaccines/therapeutic use , Drug Therapy, Combination , Leucine/analogs & derivatives , Leucine/immunology , Mice , Thymosin/immunologyABSTRACT
Tests conducted on mice of the CBA line immunized with sheep erythrocytes have brought evidence that, when introduced to the animals 24 and 48 hours after immunization, phosphemide appreciably reduces the number of cells producing the IgM- and IgG-anibodies. The maximum immunodepressive effect of phopurine was observed when this was introduced simultaneously with the antigen, and also 24 and 48 hours following immunization. Both compounds produced a change in the mass of the immuno-competent organs and reduced the number of nuclei-containing cells in the spleen throughout the entire period of investigation.