Preparation of a Prototype Inactivated Hepatitis A Virus Vaccine from Infected Cell Cultures

Abstract

Studies were conducted on the preparation, inactivation, safety, and immunogenicity of a prototype hepatitis A virus vaccine prepared from infected cell cultures. BS-C-1 cells maintained in medium 199 without serum were infected with the HM175 strain of hepatitis A virus and harvested after 21-28 days. The harvested virus preparation contained 6.8-7.4 (log 10) cell culture infectious doses/ml. After exposure to 1:4,000 formalin at 35 C, the infectivity titer decreased 10(6)-fold in 30 hr at an exponential rate, although virus was detected in 5.0-ml vaccine samples for up to three days. Three separate vaccine lots elicited antibody in all the guinea pigs given three doses. Owl monkeys given three doses of vaccine did not have any evidence of HAV infection but developed antibodies identifiable by radioimmunoassay and serum neutralization tests. After either oral or intravenous challenge with at least 10(6) monkey infectious doses of a virulent field strain of hepatitis A virus, none of the vaccinated monkeys shed virus in their feces or had elevated serum levels of alanine aminotransferase. The findings suggest that an effective inactivated whole virus hepatitis A vaccine can be prepared from cell culture.

Hepatitis transmission among the Sioux Indians of South Dakota.

“…Several prototype vaccines have been developed, and are undergoing immunogenicity trials, with efficacy trials planned in the near future. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Until such a vaccine is available, conventional measures such as the promotion of handwashing, use of IG for household contacts of acute cases, and the improvement ofgeneral sanitation will remain important priorities.…”

Guinea Pig (Cavia Porcellus) Can Be or Not Used as an Experimental Model to Study Hepatitis a Virus Infection?

“…Non-human primates are considered the principal models for HAV which more closely mimics many of the aspects of the human disease (Purcell & Emerson 2001, Deinhardt et al 1962, Dotzauer et al 1994). Due to high economical and moral concerns, the feasibility of guinea pigs (Cavia porcellus) in the experimental infection by HAV is considered among the replacement options (Binn et al 1986, Elbert et al 1992, Hornei et al 2001). …”

“…It was reported that guinea pigs (Cavia porcellus) could be used in several tests of immunogenicity, effectiveness and safety of vaccines (Binn et al 1986, Flehmig et al 1987, Elbert et al 1992, Mitchell & Galun 2003, Mitchell et al 2006) and in events related to the proper vaccine of hepatitis A (Hornei et al 2001, Burnett et al 2003.…”

Role of U.S. military research programs in the development of U.S.-licensed vaccines for naturally occurring infectious diseases

“…Dubois, and K.H. Eckels [98,99]. Analysis of strains from international sources showed antigenic similarity and indicated that a vaccine need contain only a single serotype to provide global protection against HAV.…”