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Preparation and immunogenicity of an inactivated hepatitis A vaccine
V Pellegrini1, N Fineschi, G Matteucci
1IRIS, Siena, Italy.
Abstract:
A hepatitis A vaccine was prepared by formaldehyde inactivation of purified hepatitis A virus (HAV) LSH/S strain grown on human diploid MRC-5 cells. The vaccine was devoid of residual infectivity in vitro and failed to induce in marmoset monkeys any pathological features or variations of haematological and clinical chemistry values. Infectious HAV particles were not detected in faeces and sera of the vaccinated primates by ELISA or after passages in MRC-5 cells. The immunogenicity of the vaccine was evaluated by injecting guinea-pigs with 0.8, 0.2 or 0.05 micrograms of HAV antigen adsorbed onto 0.5 and 1 mg of Al (OH)3 or 0.3 mg of AlPO4. The antibody response, measured by a competitive radioimmunoassay, was dose- and adjuvant-dependent. One injection of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced seroconversion in 100% of animals and high levels of specific and neutralizing serum antibodies. A further increase of antibody titres was observed after the second and third inoculations. These results show that this vaccine formulation is safe and immunogenic in animal models, and suggest that it should be evaluated further by human clinical studies.
Insights
This study developed a safe and effective hepatitis A vaccine (HAV) using inactivated virus. Animal studies demonstrated strong immunogenicity, paving the way for human clinical trials of this novel vaccine.
Area of Science:
- Virology
- Vaccinology
- Immunology
Background:
- Hepatitis A virus (HAV) infection poses a significant global health burden.
- Development of safe and immunogenic vaccines is crucial for disease prevention.
Purpose of the Study:
- To develop and evaluate the safety and immunogenicity of a novel inactivated hepatitis A vaccine (HAV).
- To assess the vaccine's efficacy in preclinical animal models before human trials.
Main Methods:
- Hepatitis A virus (HAV) was purified and inactivated using formaldehyde.
- Vaccine safety was assessed in marmoset monkeys, monitoring for pathological and hematological changes.
- Immunogenicity was evaluated in guinea pigs using varying antigen doses and adjuvants (Al(OH)3, AlPO4).
- Antibody responses were measured via competitive radioimmunoassay, and infectivity was confirmed absent through ELISA and cell culture passages.
Main Results:
- The inactivated HAV vaccine showed no residual infectivity in vitro or adverse effects in vaccinated marmosets.
- Guinea pigs vaccinated with AlPO4-adsorbed antigen demonstrated dose-dependent antibody responses.
- A single dose of 0.2 micrograms of AlPO4-adsorbed HAV antigen induced 100% seroconversion and high antibody titers.
- Subsequent inoculations further boosted antibody levels, indicating sustained immunogenicity.
Conclusions:
- The developed inactivated hepatitis A vaccine is safe and highly immunogenic in preclinical animal models.
- The vaccine formulation, particularly with AlPO4 adjuvant, shows promise for effective hepatitis A prevention.
- Further evaluation in human clinical studies is warranted to confirm its efficacy and safety in humans.