An affordable multideterminant plasma-derived hepatitis B virus vaccine.

A new vaccine is reported which contains hepatitis B virus (HBV) e antigen (HBeAg) and pre-S determinants, in addition to highly purified HBV surface antigen (HBsAg). The rationale for this approach depends on the following data indicating that anti-HBe and antibody to the core antigen (anti-HBc), and antibody to pre-S determinants may play an active role in preventing HBV infection: (1) active immunization of chimpanzees with HBeAg(s) devoid of detectable HBsAg protected against subsequent challenge with HBV; (2) passive immunization of chimpanzees with an anti-HBe/anti-HBc intravenous immunoglobulin devoid of anti-HBs significantly delayed and appeared to attenuate HBV infection following subsequent challenge with HBV; (3) antibody to pre-S determinants appears to be able to neutralize infective HBV. The purification procedure used for the production of the New York Blood Center vaccine was designed to accomplish a high degree of purification with minimal use of complex equipment. This may facilitate eventual utilization of the vaccine on a mass scale for prevention of the HBV carrier state in high-prevalence regions of the world. The procedure uses polyethylene glycol (PEG) precipitations and hydroxylapatite adsorption steps, followed by only a single isopycnic separation in a zonal rotor, to achieve a vaccine which is substantially free of serum proteins and detectable HBV DNA yet contains HBsAg, HBeAg and pre-S determinants. The original vaccine was inactivated by Tween 80 and formalin. Four lots passed chimpanzee safety tests; two of these have been tested in clinical trials. Recently an improved vaccine has been developed in which two heat inactivation steps are used instead of formalin inactivation. This has resulted in further improvement in yields of antigenicity and immunogenicity, and provides an additional margin of safety.