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Serum from humans (n = 646) and monkeys (n = 1867) collected during the period 1999-2013 was tested by enzyme immunoassay. Anti-HEV IgG was detected significantly more frequently (P ≥ 0.001) in rhesus macaques (Macaca mulatta) - 45.1 ± 1.6% (n = 1001) than in cynomolgus macaques (M. fascicularis) 16.2 ± 1.8% (n = 426). Single seropositive individuals were found among M. nemestrina - 4.0±2.8% (n = 50). Anti-HEV was not detected in the sera of green monkeys (Chlorocebus aethiops) - n = 162, Papio hamadryas (n = 124), and Papio anubis - n = 104. The presence of the anti-HEV IgM indicating the cases of fresh infection in Macaca mulatta - 2.1 ± 0.5% (n = 717) and M. fascicularis - 3.5 ± 1.3% (n = 266) is of great significance. The overall frequency of detection of the anti-HEV IgG among the staff of the Adler Primate Center - 6.8 ± 2.3% (n = 118) was significantly lower (P ≤ 0.001) than among the population of the Greater Sochi - 15.9% ± 1.6 (n = 528). It is important that only in patients of medical institutions (clinic, hospital, cancer center), anti-HEV IgM were detected (2.7-11.8%) along with anti-HEV IgG (15-23.5%), thereby indicating the presence of acute cases of HEV infection among this population. HEV RNA was not detected in the serum of anti-HEV IgM-positive people and monkeys. Seroepidemiological data do not confirm the assumption on the ability of seropositive monkeys of Macaca genus to be a natural reservoir of HEV infection for humans.

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There is evidence for the rather high detection rate of antibodies against hepatic E virus (HEV) was rather high in the macaques from the Adler apery in 1999-2005. Anti-HEV was detected in 232 (57.3%) out of 405 examined rhesus macaques (Macaca mulata) and in 16 (16%) out of 100 Java ones (M. fascicularis). The detection rate of anti-HEV ranged from 12.5 to 89.5%% among the rhesus macaques and from 5.9 to 37.5% among the Java ones. Class M anti-HEV was found only in 3 (4.3%) out of 69 Java macaques and in none of the rhesus ones. Of importance are the data of detection of anti-HEV in 3 (7.5%) out of 40 examined employees of the Research Institute of Medical Primatology, all 3 (18.8%) out of 10 employees looking after the monkeys that belonged to the highest-risk group. The epidemiological and epizootological aspects of this infection require further studies.

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Time course of specific humoral immunity is studied in 186 Macaca mulatta spontaneously infected with hepatitis A virus (HAV). Immunity parameters are characterized quantitatively and qualitatively and their similarity to those in human hepatitis A (HA) is demonstrated. Repeated HA was reproduced in 12 seropositive Macaca mulatta infected with HAV-MR in high doses. The disease was characterized either by periodical virus release with feces for 1.5-2 months (10(4) ID50) or by that together with a notable increase of SGPT for 1.5-4 months (10(5) ID50) without morphologic changes in the liver, indicating a lesser severity of infection. Reinfection was associated with a rapid expressed increase of class G anti-HAV titers to 20,000-74,000 and no class M antibodies. Virus release with feces in the absence of the main specific diagnostic criterion, IgM antibodies, may be epidemiologically significant. Hyperimmune sera from monkeys with reinfection are intended to be used as the antibody component of immune diagnostic agent.

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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.

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Cultural strains of hepatitis A virus (HAV) have been isolated from spontaneously infected Macaca mulatta (HAV-MM), Papio hamadryas (HAV-PH), African green monkeys Cercopithecus aethiops (HAV-CA), and patients (HAV-H). The strains replicate in continuous cells lines AGMK, 4647, Vero, and FRhk-4. AGMK and 4647 cells are the most permissive at 32 degrees C. Virus propagation was not associated with the cytopathic effect and could be detected by enzyme immunoassay (EIA), immune electron microscopy (IEM), and molecular hybridization method (MHM). The morphological and antigenic properties of the above monkey and human strains did not differ in EIA and IEM with polyclonal antibodies and for one most conservative genome sites in the VP1 domain. Cultural strains retained their pathogenicity for monkeys. HAV strains are proposed to be used as HAV antigen in immunological tests and for hepatitis A induction in monkeys.

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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.

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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.

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Data on high susceptibility of Papio hamadryas to HAV are presented. For the first time, P. hamadryas were shown to be able to respond to both natural and experimental infection developing the features typical of hepatitis A: increased aminotransferase activity, virus shedding in feces, production of anti-HAV IgG and IgM, histological liver lesions. An infection lingering for 3-4 months was observed, as well as a case of chronic experimental hepatitis A with relapse in 7 months of the disease. Virological evidence of HAV infection was obtained in both lingering and chronic disease. HAV-PH strain was isolated for the first time and is described at length. It was isolated from a baboon with spontaneous infection which did not differ from that in man by antigenic and morphological features. The virus replicated in continuous African green monkey kidney cell line (AGMK) and was pathogenic for P. hamadryas. The HAV-PH isolate can be used for modelling hepatitis A in P. hamadryas.

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Characteristics of experimental hepatitis A in Macaca fascicularis and M. mulatta produced with HAV, strain MP, isolated from M. mulatta in an outbreak of spontaneous hepatitis are presented. The HAV-MP strain induced the disease in all the animals used in the experiment. The infection was manifest, with all virological, serological, biochemical and morphological features typical of hepatitis A. In M. mulatta, the process was protracted, with virus persistence in feces for at least 4 months. Modeling of hepatitis A in Macaca monkeys using HAV-MP strain may be used for the study of the pathogenesis and trials of immune preparations.

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The results of observations on the pattern of spread of hepatitis A virus and immune response to it in African green monkeys (Cercopithecus aethiops) kept in the animal house are presented. The infection in the monkeys was found to be characterized by all virological, serological, and biochemical parameters inherent in hepatitis A virus. The results indicated that hepatitis A in monkeys may run both asymptomatic and clinically manifest course, and the spread of infection in the animal house sequentially involves most seronegative animals into the epidemic process.

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Morphological, virological and serological data characteristic of spontaneous hepatitis A in macaques and green monkeys have been presented. The disease similar to human hepatitis A was induced in M. iris macaques, with the virus isolated from spontaneously infected rhesus monkeys. Experimental model of hepatitis A in macaques is likely to be used for the testing of vaccines and antiviral preparations.

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This is the first report of virologically verified spontaneous hepatitis A in M. rhesus monkeys with severe involvement of the liver leading to the death of the animals. In 21 out of 23 dead monkeys morphological lesions in the liver have been characterized as acute hepatitis. In 6 (26%) animals no other pathological processes were found. In 15 animals hepatitis was combined with other diseases (dysentery, parasitic infestations, coronavirus infection). Antigen of hepatitis A virus was detected by an enzyme immunoassay in the intestinal contents of 8 monkeys and in the livers of 3 of them. Immune electron microscopic studies detected in the intestines some virus particles morphologically and antigenically similar to human hepatitis A virus.

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The results of examinations of stump-tailed monkeys (M. arctoides) held in captivity are presented. The presence and levels of anti-HAV and anti-HAV class M in the blood sera of monkeys were determined by the enzyme-immunoassay (EIA), and alanine aminotransferase (AIAT) activity was measured. HAV in stool specimens collected from the monkeys was detected by immune electron microscopy and EIA. In the first examination, 2 out of 10 monkeys were found to have anti-HAV and one of them to have anti-HAV class M. In repeat examination of 4 monkeys 32 days later, two of them showed an increase in AIAT and 3 had HAV in stools. In the 3rd examination in 91 days, all the four animals had anti-HAV and anti-HAV class M. Besides, three seronegative monkeys out of the ten examined initially, showed only total anti-HAV in 91 days. At the time of the 3rd blood specimen collection, 16 more monkeys were examined and all of these had anti-HAV but not anti-HAV class M. It is assumed that natural infection of stumptailed monkeys in captivity with a virus antigenically identical to HAV is possible.

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The study of the immunostimulating potency of the staphylococcal antigenic complex obtained from different strains by aqueous extraction indicated that the preparations obtained from highly virulent strains showed the lowest potency after challenge with both homologous and heterologous strains. The preparations obtained from strains with low virulence stimulated resistance to highly virulent strains to a greater extent than the preparations from the same virulent strain which was used for challenge. The necessity of revising the requirements to strains used for the production of antibacterial staphylococcal preparations is substantiated.

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The data obtained of the acute and chronic toxicity of a number of staphylococcal immune preparations are presented. The paw edema test has been shown to yield more informative results for the evaluation of acute toxicity than the method of intraperitoneal injection and LD50 determination. The paw edema test has revealed that the toxicity of corpuscular vaccine is higher than that of the preparations of water-soluble antigenic staphylococcal complexes. The chronic toxicity test has demonstrated that corpuscular vaccine, antiphagin, adsorbed toxoid and the antigenic complex have low toxicity: their multiple administration in doses exceeding the equivalent doses 30-200 times have been found to exert no influence on the increase of the weight of the animals.

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