[Characteristics of experimental models of hepatitis A in Papio hamadryas]. / Kharakteristika éksperimental'nykh modelei gepatita A na pavianakh gamadrilakh.

Hepatitis A (HA) was induced in 14 Papio hamadryas by strain VHA-PH isolated from this species of monkeys with spontaneous infection, strain VHA-MM isolated from Macaca mulatta, and a unique strain VHA-H3 isolated from a patient; this latter strain is pathogenic for Macaca mulatta in experiment. All infected seronegative animals developed a disease with virological, serological, biochemical, and morphological signs characteristic of human HA, but the duration of these signs manifestation varied. Virus in the feces and an increased level of SGPT were detected periodically starting from days 3-26 to 24-135, and in 4 monkeys even later (up to days 163-238). Morphologic changes in the liver, typical of acute hepatitis, were observed from days 10-46 to days 16-130. Strain VHA-H3 is less pathogenic for papios. HA models on Papio hamadryas infected with strains VHA-PH and VHA-MM can help solve many research and practical problems.

[An experimental study of immunity to hepatitis A in monkeys]. / Eksperimental'noe izuchenie immuniteta k gepatitu A na obez'ianakh.

In this work the experimental model of hepatitis A on monkeys, adequate to human hepatitis A, was used. Ten monkeys (6 Macaca mulatta and 4 Cercopithecus aethiops) were reinfected with different doses of hepatitis A virus (HAV) a year after recovery from spontaneous and experimental hepatitis A. The monkeys were completely resistant to the inoculation of the virus in moderate doses (10(3) ID50). The inoculation of HAV in large doses (10(4)-10(5) ID50) induced a mild form of this infection in the animals with a transient rise in the level of serum alanin aminotransferase and HAV shedding in feces, but in the absence of morphological changes in the liver. It should be specially pointed out that after the reinfection of monkeys virus shedding in feces was observed, which may be of great epidemiological importance. After reinfection the absence of IgM and a pronounced rise in the titers of IgC antibodies were observed.

[A trial of a hepatitis A cultured inactivated vaccine on rhesus macaques]. / Ispytanie kul'tural'noi inaktivirovannoi vaktsiny gepatita A na makakakh rezusakh.

In this work experimental model of hepatitis A virus (HAV) infection in macaques rhesus was used. In 6 seronegative monkeys immunized with the inactivated vaccine (3 injections of 0.3 micrograms of viral protein each at an interval of 1 month) pronounced antibody response was observed. The dynamics and titers of anti-HAV antibodies were similar to those in 5 rhesus macaques which received the active virus. But, in contrast to the latter, no IgM antibodies were detected in the immunized animals. Three months after the end of immunization the monkeys were resistant to challenge with a HAV strain pathogenic for humans (10(3) - 10(4) ID50). The monkeys had no morphological changes in the liver and no rise in the serum alanine-amino transferase activity, but exhibited transient excretion of the virus in feces, as well as stimulation of anti-HAV antibodies (in the absence of IgM antibodies). The vaccine under test proved to be safe, immunogenic and produced a protective effect.

[Experimental models of hepatitis A in macaques using viral strains isolated from man and monkeys]. / Eksperimental'nye modeli gepatita A na makakakh s ispol'zovaniem shtammov virusov, vydelennykh ot cheloveka i obez'ian.

Experimental hepatitis A (HA) models were obtained in macaca monkeys (15 M. fascicularis and 4 M. mulatta) by means of the strains of hepatitis A virus (HAV) isolated from the feces of a patient (HAV-H) and of spontaneously infected M. Mulatta (HAV-MM) and green monkeys Cercopithecus aethiops (HAV-CA). Irrespective of the strains used all seronegative macaca monkeys developed HA after intravenous-oral inoculation with the following patterns: elevation of the serum alanine aminotransferase level, HAV shedding in feces, seroconversion with the appearance of anti-HAV IgM and morphological changes in the liver characteristic of acute hepatitis. HAV in fecal samples and elevation of alanine aminotransferase were periodically detected. Periods of their discovery varied from 5-22 to 15-47 days and those of morphological changes in the liver from 9-24 to 40-83 days. The results of the experiments show that experimental HA models in Macaca monkeys are no less adequate than the previous ones developed in chimpanzees (Pan troglodytes), marmosets (Saguinus mystax) and owl monkeys (Aotus trivirgatus), but they are more readily available. Both strain HAV-H and strains from monkeys can be used for HA modelling. The models are expected to be used for studying yet unsolved problems of pathogenesis and immunogenesis, as well as for testing vaccines and antiviral drugs.

[Virus persistence in hepatitis A in monkeys]. / Persistentsiia virusa pri gepatite A obez'ian.

A long-term complex observation of 16 cynomolgus monkeys (Macaca fascicularis) and 8 African green monkeys (Cercopithecus aethiops) with spontaneous and experimental hepatitis A revealed two forms of the illness: acute and chronic. Some monkeys developed undulating chronic course of the disease consisting of 2-6 waves. Others developed relapses (1 to 3) which occurred within 2-4 or 6-11.5 months of the infection. The morphological changes in the liver persisted for 7-28 months. Alaninaminotransferase elevations in the blood and HAV shedding in feces were observed periodically for 7-20 months. HAV persistence was documented by radioimmunoassay, enzyme immunoassay, immune electron microscopy and molecular hybridization. Persisting HAV was shown to remain pathogenic for monkeys. Virological evidence of the etiological association of HAV with chronic infection and late relapses has been obtained for the first time.