ABSTRACT
Studies of the primary cultures of granulocytes, mononuclear, and monocyte-macrophage cells derived from human blood were performed using variola virus (VARV) in the doses of 0.001-0.021 PFU/cell (plaques-forming units per cell). Positive dynamics of the virus accumulation was observed only in the monocyte-macrophages with maximum values of virus concentration (5.0-5.5 Ig PFU/ml) mainly within six days after the infection. The fact of VARV replication in the monocyte-macrophages was confirmed by the data of electron microscopy. At the same time, virus vaccines when tested in doses 3.3 and 4.2 Ig PFU/ml did not show the ability to reproduce in these human cells. The people sensitivity to VARV as assessed from the data obtained on human monocyte-macrophages corresponded to -1 PFU (taking into account the smooth interaction of the virus in the body to the cells of this type), which is consistent to previously found theoretical data on the virus sensitivity. The human susceptibility to VARV assessed experimentally can be used to predict the adequacy of developed smallpox models (in vivo) based on susceptible animals. This is necessary for reliable assessment of the efficiency of development of drugs for treatment and prophylaxis of the smallpox.
Subject(s)
Macrophages/virology , Smallpox/prevention & control , Variola virus/physiology , Virion/growth & development , Adult , Animals , Antibodies, Viral/blood , Granulocytes/immunology , Humans , Macrophages/ultrastructure , Male , Microscopy, Electron , Organ Specificity , Primary Cell Culture , Smallpox/blood , Smallpox/immunology , Smallpox/virology , Smallpox Vaccine/pharmacology , Variola virus/ultrastructure , Virion/ultrastructure , Virus ReplicationABSTRACT
A genetic construct of the human interleukin-2 (IL-2) gene within vaccinia virus (L-IVP strain) has been designed. The authors show the capacity of CV-1 cells infected with the recombinant vaccinia virus VV-SIL2 to secrete human IL-2 into the culture medium. Human IL-2 has been detected by immunoblotting. The sera from the animals immunized with the recombinant virus VV-SIL2 exhibited both human IL-2 and its antibodies throughout the observation period. This recombinant virus immunization induced both humoral and cell-mediated immune responses to human IL-2; the observed changes in the concentrations of cytokines are likely to suggest that the response predominantly followed a Th1 pathway. The study construct was nontoxic at the used concentrations and administration routes. The findings point that it is promising to investigate the adjuvant properties of the recombinant VV-SIL2 vaccine-based preparation for immunization in combination with various vaccines and to study this construct in therapy for cancer diseases.
Subject(s)
Antibodies, Viral/blood , Immunization , Interleukin-2/genetics , Interleukin-2/immunology , Poxviridae Infections/blood , Poxviridae Infections/immunology , Smallpox Vaccine/immunology , Vaccinia virus/genetics , Vaccinia virus/immunology , Animals , Cell Line , Cytokines/blood , Humans , Immunoenzyme Techniques , Injections, Subcutaneous , Interleukin-2/blood , Lymphocyte Activation , Male , Mice , Mice, Inbred BALB C , Smallpox Vaccine/administration & dosage , Smallpox Vaccine/genetics , Spleen/immunology , Th1 Cells/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunologyABSTRACT
The protective properties of artificial mycobacterial particles versus BCG vaccine were studied in laboratory animals with experimental tuberculosis. The findings of the decreased rate of a tuberculous process and on the increased mean life span in animals inoculated with M. bovis suggest that immunization of guinea-pigs with mycobacterial particles promotes the enhanced development of antituberculous immunity in the animals. The paper proposes a promising method for designing artificial immunogens, the high-polymer antigenic structures that imitates mycobacterial particles.
