Status: marketed in Europe and elsewhere, not U.S.

Organizations involved:

Sanofi Aventis S.A. – Manuf.; R&D; Tech.; Intl. mark.

Sanofi Pasteur MSD - Europe mark.

Cross ref.: See the Hepatitis A Vaccine Products entry and the entries for the two U.S. marketed hepatitis A vaccines: Havrix, from SmithKline Beecham Biologicals S.A. and Vaqta from Merck & Co., Inc. See also Viatim (Vivaxim), a combination vaccine of which Avaxim is a component.

Description: Hepatitis A Virus Vaccine, Inactivated or Avaxim is an aqueous formulation of inactivated whole hepatitis A virus (HAV) prepared from attenuated hepatitis A virus GBM strain cultured in MRC-5 human diploid fibroblasts inactivated with formalin/formaldehyde and adsorbed onto adjuvant.

Each 0.5 mL dose of Avaxim contains inactivated hepatitis A virus, 160 AV antigen units (in the absence of an international standardized reference, using an in-house reference). Other constituents include aluminum hydroxide, 0.3 mg; 2-phenoxyethanol, 2.5 µg; formaldehyde, 12.5 µg; Hank’s medium 199; water for injection; and neomycin, trace amounts. Hydrochloric acid or sodium hydroxide may be used to adjust the pH of the fluid content, i.e., Hanks medium 199 plus water for injection. Some sources, perhaps not as recent, report the vaccine contains traces of polysorbate 80 (Tween 80).

This vaccine is also a component of a bivalent vaccine. See the Viatim (Vivaxim) entry. This is also marketed primarily as a traveler’s vaccine and combines protection from hepatitis A with protection from Salmonella typhi infection.

Biological.: The HAV GBM strain was isolated in 1975 from a patient during an outbreak in Gomaringen, Germany, by B. Flehmig, Tübingen University. The virus was adapted and propagated by culture in primary human kidney cells, followed by adaptation in human diploid fibroblast cells and human diploid MRC-5 cells. The resulting culture-adapted virus showed some mutations, with these correlating with attenuation when inoculated into chimpanzees. GBM strain-derived vaccines have been shown immunogenic in guinea pigs, goats, mice and humans.

Nomenclature: Hepatitis A Virus Vaccine/Sanofi [BIO]; Hepatitis A Virus Vaccine, Inactivated [FDA, if it was approved in U.S.]; Avaxim [TR]

Companies.: Avaxim is manufactured by Sanofi Aventis S.A. (formerly Aventis Pasteur S.A.) The vaccine is marketed in France and other European countries by Sanofi Pasteur MSD Ltd. (formerly Aventis Pasteur MSD), a joint venture of Sanofi Aventis S.A. and Merck & Co., Inc. The vaccine is marketed in other countries by Sanofi Aventis S.A. affiliates.

Manufacture: The virus is cultured, harvested by physical methods, further purified, inactivated with formalin (formaldehyde), and adsorbed onto aluminum hydroxide adjuvant. Apparently, after culture in MRC-5 fibroblasts cells using Hank’s medium 199, inactivation with formalin/formaldehyde and purification, bulk vaccine is adjusted for antigen content according to prior results and the use of an in-house enzyme immunoassay in comparison with in-house reference materials. No international reference antigen preparation was available at that time of Avaxim development. Antigen is adsorbed to aluminium hydroxide, 2-phenoxyethanol is added as an antimicrobial preservative, and antigen concentration is adjusted using Hank’s medium 199 and sterile water for injection. Potency is reported in European hepatitis A units (EAU).

Status: Avaxim is marketed in many European and other countries worldwide. It has not received centralized European Union approval.

Medical: Avaxim is administered by intramuscular (IM) injection. The primary vaccination a involves a dose of vaccine, followed by a booster injection 6 to 12 months later for adults over 15 years of age; or 6 months later for children between 2 and 15 years of age. As with other inactivated hepatitis A vaccines, immunological priming is achieved in virtually all vaccines after a single primary immunization, and this may be reinforced by a booster vaccination administered 6–36 months after the primary vaccination.

Trials: Clinical trials began in 1991 and tested Avaxim containing doses ranging from 20-320 European hepatitis A units (EAU).

Market: Sanofi Pasteur’s hepatitis A virus vaccines, Avaxim and Viatim (Vivaxim), have captured ~10–15% of the global market for immunization against hepatitis A (despite not being marketed in the U.S.).

In April 2005, the U.K. National Health Service (NHS) cost was reported to be £20.63 (~$39.50).