Low Immunogenicity of Recombinant Hepatitis B Vaccine Derived from Hansenula polymorpha in Adults Aged Over 40 Years

Abstract

Abstract. The Brazilian recombinant hepatitis B vaccine (VrHB-IB) is based on the expression of the recombinant antigen in Hansenula polymorpha yeast cells. Currently, data on the immunogenicity of this vaccine in older adults are nonexistent. This study aimed to evaluate the immunogenicity of VrHB-IB in adults over 40 years of age. From May to October 2011, 235 rural settlers between 2 and 93 years of age from the State of Goias in Brazil were eligible for vaccination. Of these, 180 accepted the first dose of the vaccine and 106 (58.9%) completed the vaccination schedule. Multivariate analysis revealed that individuals ≥ 40 years of age responded significantly less well to vaccination than younger adults. Also, a greater proportion of male nonresponders was observed (versus women; P = 0.02). These results point to the need for better evaluation of the immunogenicity of VrHB-IB in older adults.Vaccination against hepatitis B is the safest and most effective method of reducing the incidence and prevalence of infection with hepatitis B virus (HBV).1 Indeed, HBV vaccination confers protection in over 90% of subjects who receive it.2 The first-generation HBV vaccine, which was produced from human HBV surface antigen (HBsAg) plasma from chronically infected patients, became commercially available in the early 1980s and is still used in some countries. 3The second-generation vaccine, also marketed in the 1980s, is produced using recombinant DNA technology. This vaccine is safe and effective, and allows for unlimited production and widespread distribution throughout the world. Currently, many countries produce the HBV vaccine using this technology, and various expression systems have been used to obtain recombinant HBsAg.1,4 Engerix-B, the gold-standard vaccine, uses Saccharomyces cerevisiae as the expression system for recombinant HBsAg. In Brazil, the Brazilian recombinant hepatitis B vaccine (VrHB-IB) is obtained by culturing genetically engineered Hansenula polymorpha yeast cells with the HBsAg gene. Initially, this vaccine was produced as a recombinant antigen (concentration 20 μg/mL). However, research has shown that in adults 30-40 years of age, the immunogenicity of the Brazilian vaccine is not equivalent to the gold-standard vaccine (Engerix B), 5 and the concentration of HBsAg was therefore increased to 25 μg/mL. A clinical trial comparing the immunogenicity of VrHB-B with Engerix-B in patients in this age group found that the vaccine produced in Brazil at the current concentration is equivalent to the gold standard. The aim of our study was to evaluate the immunogenicity of VrHB-IB vaccination in rural settlers in central Brazil. Rural settlers who were susceptible to HBV comprised the vaccination group, and most of them were > 40 years of age. At present, published studies on the immunogenicity of the Brazilian HBV vaccine in adults in this age group are rare.From May to October 2011, 467 rural settlers from the southwest region of the State of Goias, central Brazil, were recruited. All agreed to participat...

Prevalence, Risk Factors and Vaccine Response against Hepatitis B in People Aged 50 Years or Older

“…The lower efficacy of hepatitis B vaccines in older individuals has been described in the literature and is a worrying phenomenon. Studies conducted worldwide in the age group of 50 years or older have shown higher rates of non-response or lower vaccine responsiveness after a complete primary immunization schedule [ 15 , 16 ]. In addition, aging of the immune system negatively interferes with the vaccine response against hepatitis B, causing several changes in the individual’s immune response [ 16 , 45 ].…”

“…For the clinical trial, it was considered that 60% [ 15 ] of individuals aged 50 years or older would respond to the conventional vaccine and 80% to the reinforced dose, with a statistical power of 80% (β = 20%) and a significance level of 95% (α < 0.05), and 30% were added to the calculation to replace losses. Therefore, 240 people would be needed: 120 for the intervention group and 120 for the comparison group.…”

“…Studies conducted with middle-aged and elderly adults showed lower vaccine response against hepatitis B using the conventional scheme [ 15 , 16 ]. On the other hand, the reinforced regimen is reported in the literature as a successful strategy to induce the production of anti-HBs protective titers in individuals with a lower vaccine response [ 17 , 18 ].…”