Further evaluation of the safety and protective efficacy of live attenuated hepatitis A vaccine (H2-strain) in humans.

A study on the possibility of transmission of live hepatitis A vaccine (H2-strain) from vaccinees to nonvaccinees was conducted. As a result, no seroconversion was found among 87 seronegative nonvaccinees, who had a close contact with their 141 subcutaneously vaccinated classmates nor was it found among 101 seronegative children administered the vaccine orally. The above fundings suggest that by losing the ability to be transmitted orally the vaccine virus may result in a decreasing possibility of dissemination among contacts. A 4-year study on the protective efficacy of the H2-strain vaccine was done at 11 primary schools starting at 1991 in Shaoxing County. Since then, there has been no hepatitis A reported among 18102 cumulative person-years in the vaccination group, while 495 cases occurred among 242168 cumulative person-years in the control groups. A large scale vaccination with a cumulative vaccination coverage of 89.45% was carried out in Jiaojiang City among children 1-15 years old. Hepatitis A in this age group in the city, which had 12-87 cases per annum with an average of 32 for 8 years before vaccination, decreased drastically to 0-1 cases after vaccination. The protective efficacy of H2-strain vaccine proved to be satisfactory.

[Hereditable characteristics of attenuated live hepatitis A virus H2 strain].

The toxicity of attenuated hepatitis A virus H2 strain was not increased in testing KMB 17 cells of 5 consecutive generations of monkeys at 36 degrees C. After injection of attenuated live hepatitis A virus H2 strain in humans, no abnormality was noted. Serum hepatitis A antigen was positive after 38 children aged 3-9 years were given oral 10(6.5) TCKD50, whereas it was 100% positive in the group of same age after percutaneous vaccination. Noninfection of oral administration is an important hereditable characteristic differentiation from wild strains.

Studies in monkeys of attenuated hepatitis A variants.

Three HAV variants, H2M20(35 degrees C), H2M20(35 degrees C) and H2M20K5(32 degrees C), were developed by passage in different tissue culture cells and at different temperatures. Virulence for monkeys was assessed by inoculating each of the variants into four monkeys. Weekly bleeding through 16 weeks post-inoculation was assayed for anti-HAV titers and SGPT as well as LDH5 activities. And in some monkeys liver biopsies were also studied. Seroconversion was induced in all of the inoculated monkeys. The anti-HAV titers tested at 16 weeks post-inoculation were: 40-640 with H2M20(35 degrees C), 40-160 with H2M20(32 degrees C) and 20-40 with H2M20K5(32 degrees C). These variants showed different levels of virulence/attenuation for monkeys. Variant H2M20(35 degrees C) showed no evidence of attenuation, variant H2M20(32 degrees C) retained slight virulence and variant H2M20K5(32 degrees C) showed no evidence of virulence for monkeys. Criteria are proposed for assay of HAV virulence tested in monkeys.

Inapparent infection of hepatitis A virus.

To detect inapparent infection with hepatitis A virus, serial sera were collected from patients with hepatitis A and their contacts in two waterborne epidemics in China. Epidemic 1 occurred in a rural village near Hangzhou during August 1978-January 1979, and epidemic 2 took place in a rural primary school in Pinghu County in Zhejiang in April-May 1985. These sera were tested for antibodies against hepatitis A virus (anti-HAV), serum glutamic pyruvic transaminase (SGPT) activity, and icteric index. Feces also were collected in epidemic 1 to test for hepatitis A virus antigen. Both anti-HAV immunoglobulin M (IgM) and total anti-HAV were assayed in sera from "healthy persons" (symptomless persons without icterus and with normal SGPT level) who were in close contact with hepatitis A patients. In epidemic 1, among 18 "healthy persons", 12 were anti-HAV IgM positive, two were immune, and four susceptibles escaped infection. In epidemic 2, among 32 "healthy children", three were anti-HAV IgM positive, five had been infected by hepatitis A virus in the past, and 24 were not infected. These results demonstrate that inapparent infections occur along with overt and subclinical infections during epidemics of hepatitis A. The proportions of inapparent, subclinical, and overt infections were, respectively, 34.3%, 45.7%, and 20% in epidemic 1, and 25%, 50%, and 25% in epidemic 2. In addition, hepatitis A virus particles were demonstrated in the feces of all infected subjects who were examined and who included all levels of clinical response. These particles were identified with immuno-electron microscopy and enzyme-linked immunoassay.

Patterns of shedding of hepatitis A virus antigen in feces and of antibody responses in patients with naturally acquired type A hepatitis.

Serial stools and sera from 13 patients with hepatitis A were collected during an epidemic in 1978 in a rural village near Hangzhou, China, and were studied to determine the patterns of shedding of hepatitis A antigen (HAAg) and of antibody response in some cases. Of 44 stool specimens, 31 were HAAg-positive by a radioimmunoprecipitation-polyethylene glycol assay. The highest percentage of HAAg positivity was in stools collected one week before and one week after the peak elevation of serum glutamic pyruvic transaminase (SGPT) levels, and peak HAAg shedding in each patient usually occurred in the early stools. Fecal shedding of HAAg was detected as early as day 19 before peak elevation in SGPT level and as late as day 11 afterward and continued for at least 25 days. The pattern of HAAg shedding in feces and of complement-fixation and immune adherence antibody response in relation to the change in SGPT activity and jaundice in four patients with hepatitis A was demonstrated.