LAUSR

Current status regarding hepatitis B vaccine In general, current immunization strategies against hepatitis B virus (HBV) are safe and efficient (>95% protection) [1]. The available US FDA approved HBV vaccines require threeor four-dose series over a 6to 12-month period to obtain the most effective protection [2]. These formulations are based on recombinant hepatitis B surface antigen (HBsAg), which self-assembles into immunogenic virus-like particles (VLPs) [3]. VLPs consist of the virus capsid or envelope proteins that mimic the organization of the native viruses but lack the viral genome [4]. In contrast to live-attenuated virus vaccines, VLPs are unable to replicate which attributes to their high safety profile. So far, there are only few VLP-based vaccines on the market. These include the above-mentioned prophylactic vaccines against HBV (e.g., Engerix) along with Cervarix and Gardasil against the human papillomavirus (HPV) [5]. Unfortunately, recombinant proteins display a limited immunogenicity and require additional adjuvants to increase the level of protection [6]. Likely the oldest and most widely used vaccine adjuvant is aluminium hydroxide or -phosphate, referred to as alum [7]. The mechanism of action behind the use of alum as an adjuvant has been poorly understood until a few years ago [8,9]. It has been shown that alum activates the NLR family, pyrin domain containing 3 (NLRP3) inflammasone subsequently leading to the release of immune mediators and the activation of antigen-presenting cells (APCs) [9]. Immunization with alum-based hepatitis B vaccines induce a humoral T H 2-directed immune response, which results in the generation of neutralizing antibodies against HBsAg and viral clearance during the acute phase of infection [10]. In contrast, the eradication of chronic HBV infections relies on the induction of robust CD4 and CD8 T-cell responses [11,12]. Thus, alum-based vaccines are mainly suitable for prophylactic vaccination in industrialized countries, which have the access to a regulated healthcare with a universal immunization program. Individuals in endemic countries often do not have access to three consecutive immunizations [13]. Consequently, single-dose HBV vaccines that induce T H 1-type responses inherit the potential to significantly promote adherence to immunization and protection against HBV infection [14].