RESUMO
The development of the formalin-inactivated hepatitis A vaccine, VAQTA, culminates nearly two decades of the basic science studies of VAQTA in hepatitis A virology at the MRL. The master seed virus for production of VAQTA is derived from the F'(P18) variant of the strain CR326F which has been studied in human clinical trials and shown to the highly attenuated. The antigen is highly purified to make possible the consistency and thoroughness of its inactivation by formalin. Phase I clinical studies of VAQTA were initiated in 1989 and have progressed since that time to the recent Phase III clinical trials which demonstrated efficacy of a single dose of the vaccine in preventing clinical hepatitis A disease in pediatric populations in Monroe, NY.
Assuntos
Hepatovirus/imunologia , Vacinas contra Hepatite Viral/biossíntese , Animais , Formaldeído , Vacinas contra Hepatite A , Humanos , Vacinas de Produtos Inativados/biossínteseRESUMO
Hepatitis A virus (HAV) strain CR326, adapted to grow in LLC-MK2 cells, was highly purified, inactivated with formalin, adsorbed to alum, and tested for capacity to induce antibody to HAV in both mice and marmosets. The minimum dose of HAV antigen necessary to produce antibody in 50% of mice was 10 ng. As little as three doses of 1 ng each produced antibody in 50% of marmosets. Further, all marmosets with any detectable antibody to HAV, as a result of vaccination, were protected against virulent infection on challenge with HAV. Thus a highly efficacious, inactivated hepatitis A vaccine can be produced from virus grown in cell culture. Although LLC-MK2 cells are unacceptable for use in human vaccine preparation, HAV can also be prepared in a similar manner in MRC-5 cells, which are acceptable for human vaccine manufacture.
Assuntos
Hepatite A/prevenção & controle , Anticorpos Anti-Hepatite/biossíntese , Hepatovirus/imunologia , Vacinas contra Hepatite Viral/imunologia , Animais , Antígenos Virais/análise , Linhagem Celular , Feminino , Hepatite A/imunologia , Anticorpos Anti-Hepatite A , Antígenos da Hepatite A , Hepatovirus/crescimento & desenvolvimento , Humanos , Camundongos , Camundongos Endogâmicos ICR , Saguinus , Vacinação , Vacinas Atenuadas/imunologiaRESUMO
Human hepatitis A virus was attenuated in virulence for chimpanzees by passage in FRhK6 and human diploid lung fibroblast cell cultures. A number of variants were developed by passage in cell cultures which showed different levels of virulence/attenuation for chimpanzees. These results were compared to those obtained with marmosets and reported previously. In general, most variants behaved similarly in the two animal types. Two chimpanzees which gave vaccine-like responses following inoculation with HAV cell culture variants were challenged with virulent HAV. Both animals were immune to HAV infection. These findings provide further evidence for the feasibility of developing live, attenuated vaccines against human hepatitis A.
