. "Appendix H: Prospects for Immunizing Against Hepatitis B Virus." New Vaccine Development: Establishing Priorities: Volume I, Diseases of Importance in the United States. Washington, DC: The National Academies Press, 1985.
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New Vaccine Development Establishing Priorities, Volume I: Diseases of Importance in the United States
hundred HBV infections in newborns is symptomatic (Schweitzer et al., 1973; Stevens et al., 1975).
Approximately 10 percent of healthy adults infected with HBV develop a chronic carrier state that may be either asymptomatic or result in chronic active hepatitis. Chronic infection can follow HBV infection and is most common in immunosuppressed adults (e.g., dialysis patients) and newborn infants (Prince et al., 1978; Schweitzer et al., 1973; Stevens et al., 1975). Chronic infection may result (usually after a period of many years) in cirrhosis or primary hepatocellular carcinoma, either of which can lead to death.
HBV is a small (42 nanometer) virus particle consisting of an outer coat and a central core with an unusual circular, partially double-stranded DNA (Dane et al., 1970; Gerin and Wai-Kuo Shih, 1978; Robinson, 1978). The central core contains two antigenic components, the core antigen (HBcAg) and a soluble component of the core antigen, the so-called e antigen (HBeAg). The coat protein is designated the surface antigen (HBsAg) of the virus. In addition to the whole virus particle, the blood of infected individuals contains smaller (20 to 22 nanometer) spherical and tubular forms that consist entirely of HBsAg. HBsAg has several major antigenic determinants. The a antigen is shared by virtually all strains of HBV. In addition, there are two sets of mutually exclusive antigenic determinants (d/y and w/r) that, in combination, produce the four major viral subtypes, adw, adr, ayw and ayr. Additional subtype classifications and variants of each of the above major determinants have been described, but their importance for HBV infection or for immunity to infection is unclear (Gerin et al., 1982).
Host Immune Responses
The immune response to HBV infection involves antibody production to all the HBV antigens: anti-HBc, anti-HBe, and anti-HBs. Anti-HBs usually appears only after resolution of HBsAg infection and is the only antibody that is considered protective (Francis and Maynard, 1979). nata/perinatal and anti-HBe may be present during acute or chronic HBV infection, as well as following resolution, and thus appear to play no part in protection against HBV. Individuals who recover from HBV infection usually develop substantial anti-HBs levels, which probably persist for life. The major humoral immune response following infection is to the common a antigenic component (anti-HBs/a) (McAuliffe et al., 1982). Thus, most individuals who have recovered from infection with one subtype of HBV will have subtype cross-protection. Rarely, anti-HBs/a fails to develop; when this occurs, the patient may remain susceptible to the other subtypes.