Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

Abstract

The immunogenicity and safety of a new recombinant hepatitis B vaccine from theButang® hepatitis B vaccine has been developed and is produced by Instituto Butantan (IB), with genetic engineering technology, using Hansenulla polymorpha yeast cells. The advantage of this yeast expression system as compared to other expression systems (such as Saccharomyces cerevisiae) is that expression is estimated to be 4 to 10 times higher, helping to decrease the production costs (Hieu et al. 2002). The vaccine contains (in 1 ml) 20 µg of HBsAg, aluminium hydroxide up to 1.25 mg (in Aluminium), and thimerosal 0.05 mg. In pre-licensure studies Butang showed low reactogenicity and good immunogenicity in adults (Costa et al. 1997, Ioshimoto et al. 1999, but additional studies were considered necessary. We report the results of a study conducted to assess the performance of the Butantan hepatitis B vaccine, compared to Engerix B®, which is produced using as expression system S. cerevisiae and widely used and acknowledged as safe and immunogenic both in Brazil and abroad. Development and production of hepatitis B vaccine by IB is part of a project to strengthen the Brazilian vaccine industry, a policy that has been pursued by the Brazilian NIP as a means to decrease vulnerability to market uncertainties. In the past, immunization activities have been jeopardized by insufficient availability of vaccines from international manufacturers. The capacity to both produce a vaccine and demonstrate its satisfactory performance with high scientific standards is strategic for developing countries. MATERIALS AND METHODSStudy design -This was a double-blind, prospective equivalence study in three centers in Brazil to assess and compare the immunogenicity of a Brazilian hepatitis B recombinant vaccine (Butang®, 20 µg/ml), to a commercially available vaccine as an active control (Engerix B®, 20 µg/ ml). Three centers in different regions of the country followed the same research protocol and addressed differ-

Eficácia e segurança da vacina brasileira contra hepatite B em recém-nascidos

“…The first trial, combined with the results reported by Martins et al, 6 led to an increase in concentration of antigen in the vaccine, and the results of the following trial confirmed the expected increase in immunogenicity of the reformulated product. Our present results in newborns, along with those of another trial conducted simultaneously, by the same team, in a sample of adults, allow us to conclude that the performance of VrHB-IB is identical to that of the reference vaccine, warranting its large-scale use in the control of an important endemic disease of in Brazil.…”

“…Subsequent trials have shown VrHB-IB to be equivalent in efficacy to the reference vaccine in children from one to 11 years of age, "less immunogenic, but acceptable for use in newborns, adolescents, and young adults," and significantly less immunogenic in adults aged 31 to 40 years. 6 In light of these results, the manufacturer has increased the concentration of antigen in the vaccine from 20 to 25μg/ml. This has generated the need for further efficacy trials for the vaccine, not only focusing on the group in which the difference in immunogenicity was greatest -adults -but also on newborns, the target group of National Immunization Program.…”

Presence of maternal anti-HBs antibodies does not influence hepatitis B vaccine response in Brazilian neonates

“…The advantage of this yeast expression system when compared to other expression systems (such as Saccharomyces cerevisiae) is that its expression is 4-10 times higher, reducing the production costs (Hieu et al 2002). This vaccine was introduced in the National Immunization Program in 2001 (MS 2003) and it is highly immunogenic in individuals less than 30 years of age (Baldy et al 2004, Martins et al 2004, Oliveira et al 2006.…”

Imunogenicidade da vacina brasileira contra hepatite B em adultos

“…However, the response among adults aged 31 to 40 years was unsatisfactory, with 79.9% of subjects becoming seroproteced, compared to 92.5% using Engerix B®. 9 It was therefore concluded that the IB vaccine should be improved before it could safely be used in adults. Instituto Butantan thus reformulated the vaccine as an attempt to increase its immunogenicity.…”