Successful Memory Response following a Booster Dose with a Virosome-Formulated Hepatitis A Vaccine Delayed Up to 11 Years

Abstract

Boosting adult travelers with the virosome-formulated, aluminum-free hepatitis A vaccine Epaxal up to 128 months after a single primary dose confers full protection against hepatitis A, even in travelers aged 50 years and above. Delaying the booster dose did not influence the immune memory response to Epaxal.Adults traveling from regions where the prevalence of hepatitis A is low to regions where it is high are at risk of acquiring symptomatic hepatitis A virus (HAV) infection (1). Long-lasting protection against HAV is, by recommendation, achieved with administration of 2 vaccine doses 6 to 18 months apart (12). In practice, many travelers do not return to see their doctors within the recommended time for the second (booster) dose, and therefore, defining the maximum interval between the two doses still conveying long-term seroprotection is of importance. Several studies using an aluminum-absorbed HAV vaccine (Havrix) and comparing various lengths of delay of the second dose (Ն24 months [9] or up to 8 years [8] after a single primary dose) have shown comparable memory responses irrespective of the interval between the two doses. A single dose of Epaxal, the only aluminum-free virosomal HAV vaccine currently available, is highly immunogenic (3). Two doses of Epaxal administered 12 months apart give adults a real-time protection of at least 9 to 11 years, which is predicted to last for at least 30 years in Ն95% of individuals (4).A study in 1999 showed that Epaxal is highly immunogenic when a booster is given 18 to 54 months after the primary dose, indicating that a delay in the administration of the booster of up to 54 months does not lead to loss of immunogenicity (2). A subsequent study in 2006 investigated the immunogenicity of an Epaxal booster administered Ն5 years after the primary immunization. This report presents the results from that 2006 study but as a combined analysis of both the 1999 and 2006 studies and evaluates the level of memory response to Epaxal when given as a booster dose 9 to 128 months (0.8 to 10.7 years) after the primary dose. Previously unpublished results from the 1999 study evaluating the postbooster immune response in a subgroup 9 to 17 months after the primary immunization are also included.Both studies were noncomparative, open-label, and singlecenter studies and were performed at the Swiss Tropical and Public Health Institute (STPH) in Basel, Switzerland; they were approved by the Ethics Committee of Basel EKBB (Basel, Switzerland) and conducted in compliance with the Declaration of Helsinki. All subjects provided informed consent before study entry.The study population included subjects who had received Epaxal primary immunization at the STPH travel clinic but had not received a booster dose for Ն9 months (in the case of the 1999 study) or Ն5 years (in the case of the 2006 study). The exclusion criteria were as previously described (2). All participants received a booster dose of 0.5 ml Epaxal (containing Ն24 IU of HAV antigen; Crucell Switzerland AG) supplied in ready-to-use s...

Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines – A systematic review

“…Information on long-term persistence after administration of a single dose of vaccine in children is limited, but has been documented in adults 76-78 . This information would suggest that protective anti-HAV antibody levels after a single dose of inactivated hepatitis A vaccine can persist for up to 11 y.…”

A single dose of inactivated hepatitis A vaccine promotes HAV-specific memory cellular response similar to that induced by a natural infection

“…A single dose schedule would remove barriers to the use of these vaccines for public health purposes by reducing the cost associated with immunization. The efficacy and safety of both one-and two-dose inactivated HAV vaccines have already been established [11][12][13][14][15]. At present, two Latin American countries have adopted single dose hepatitis A childhood immunization programs.…”

“…Two of the longest follow-up studies in adults reported the persistence of anti-HAV antibodies up to at least 17 years after receiving a monovalent inactivated HAV vaccine (Havrix TM , GlaxoSmithKline Vaccines, Belgium) according to a two-dose schedule. Hens and colleagues [44] projected duration of protection of at least 25 years in ≥95% of the vaccines [10,14,15]. However, only humoral responses have been considered when verifying protection; cellular responses have not been assessed.…”

Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

“…16 One study showed a memory response up to 11 y with a booster dose of virosome-formulated inactivated hepatitis A vaccine. 17 A memory response was also seen in children who had waning immunity following H 2 vaccination and had become seronegative. These children showed a robust antibody response when vaccinated 6 y following their initial H 2 vaccine immunization.…”