Comparison of virulence for guinea pigs and mice of different Coxiella burnetii phase I strains.

Virulence of four Coxiella burnettii phase I strains associated with acute (Nine Mile and Luga strains) and chronic (S and Priscilla strains) forms of Q fever, respectively, for outbred guinea pigs and inbred BALB/c mice was compared. In guinea pigs exposed to infectious aerosol, virulence of the strains Nine Mile, Luga and S was similar, because they all caused lethal infection and high febrile reaction (FR). By contrast, exposure to similar doses of the strain Priscilla resulted in the non-lethal infection manifested only by low, dispersed and protracted FR during a 20 day-period of observation. Lower virulence of the strain Priscilla than of the strains Nine Mile and S was observed also in guinea pigs infected intraperitoneally (ip). In mice, comparable degree of multiplication in the spleen on day 6 post ip infection was observed with the strains Nine Mile, Luga and S, but not with the strain Priscilla, namely when lower infectious doses were used. Whereas the highest doses (10(7) EID50) of the strains Nine Mile and S were lethal for mice during the second week post infection (p.i.), the strains Luga and Priscilla did not kill mice with 10-times lower (10(6) EID50) doses. At the same time agglutination antibody response detected 4 weeks p.i. was very similar in guinea pigs with all strains under study and in mice it did not differ markedly, reflecting the infectious dose used.

[The dynamics of the morphological changes in the tissues after the subcutaneous administration of vaccines against Q fever]. / Dinamika morfologicheskikh izmenenii v tkaniakh posle podkozhnogo vvedeniia vaktsin protiv Ku-likhoradki.

The comparative study of the dynamics of morphological changes in tissues of guinea pigs after the subcutaneous injection of chemical, live and combined vaccines against Q fever during the period from 12 hours to 90 days was made. All vaccines under study were shown to produce a pronounced local damaging effect. Two periods were tentatively discriminated in the dynamics of changes: the early phase (till 48 hours) and the late phase (days 2-90). At the early stage the most pronounced changes were registered after the injection of the combined vaccine. At the late phase the use of the chemical and combined vaccines was accompanied by the appearance of secondary hemorrhages into newly formed connective tissue. Starting from day 30, practically no deviation from the normal state of tissues were registered at the site of injection.

Multistep scheme for testing immunomodulatory substances.

The presented multistep program for testing immunomodulatory properties of biological response modifiers offers the possibility to evaluate multilaterally the modulatory potential of the tested preparations and to obtain basic data concerning their acute immunotoxicity. The scheme is divided into four stages: screening, optimalization, modelling, and analytical stage, each of which can be carried out separately on a relatively individual basis. This division considers the effect of the preparation on basic functions of the cells participating in the network of immunoregulation, the influence on the course of the immune response, modulation of the reactivity of the immune system affected by a 'non-immunological' phenomenon, as well as changes in protein repertoire produced by different systems of cells exposed to the tested preparation and/or the immunogenic signal. Detailed toxicological evaluation should be performed separately from immunopharmacological evaluation, keeping in mind differences in the application of the substances and the animal model involved. Incorporation of mathematical modelling and computer analysis of the results obtained by using the scheme may prove valuable in solving problems associated with potential modulation of the host immune system in clinically significant situations.

Onset and duration of immunity in guinea pigs and mice induced with different Q fever vaccines.

Protective effects of different types of Q fever vaccines, namely untreated Coxiella burnetii phase I cells (Cb I) or Cb I cells treated with chloroform-methanol (CM) mixture (Cb I-CM) and of a Q fever chemovaccine obtained by trichloroacetic acid extraction (TCAE) from intact Cb I cells, were compared in mice and guinea pigs at different intervals after intraperitoneal (i.p.) or subcutaneous (s.c.) immunizations. The highest degree of protection at all intervals studied was achieved with Cb I cells, irrespective of the route of immunization and i.p. or aerosol challenge. This vaccine exerted a protective effect in guinea pigs and mice as early as after one or two weeks post-immunization, the effect lasting for at least 40 weeks in mice (i.p. challenge) and 12 months in guinea pigs (aerosol challenge). Addition of small amount of Cb I cells to TCAE increased resistance of guinea pigs to aerosol challenge. Degree, onset and duration of protection to either type of virulent challenge afforded by Cb I-CM cells and TCAE was similar, but when compared with that of Cb I cells it was lower, started later (from the 2nd week in guinea pigs and the 3rd week in mice), and in mice it lasted for a shorter period (20 weeks only). The resistance to virulent challenge in guinea pigs did not depend on the levels of microagglutination (MA) antibodies and in mice it was reflected by delayed type hypersensitivity (DTH) reaction and adoptively transferred splenocytes, rather than by MA antibody titres and passive transfer of immune sera to recipient mice.(ABSTRACT TRUNCATED AT 250 WORDS)

[Resistance to the Venezuelan equine encephalomyelitis virus in immunization with live tularemia vaccine]. / Rezistentnost' k virusu venesueél'skogo éntsefalomielita loshadei pri immunizatsii zhivoi tuliaremiinoi vaktsinoi.

Guinea pigs immunized with live tularemia vaccine have been found to possess pronounced resistance to Venezuelan equine encephalomyelitis virus infection. Antiviral resistance induced by the vaccine has been found to persist for 1 month. One of the possible mechanisms, though not the only one, of this resistance is the stimulation of macrophages by tularemia vaccine, which results in the enhancement of their resistance to the cytotoxic action of the virus.