The ability of Hepatitis B surface antigen DNA vaccine to elicit cell-mediated immune responses, but not antibody responses, was affected by the deglysosylation of S antigen

Department of Infectious Diseases, Nanjing Medical University, and China-US Vaccine Research Center, Jiangsu Province Hospital, Nanjing 210029, China.
Vaccine (Impact Factor: 3.62). 05/2008; 26(40):5145-52. DOI: 10.1016/j.vaccine.2008.03.072
Source: PubMed

ABSTRACT Hepatitis B Virus (HBV) infection remains a major worldwide infectious disease with serious long-term morbidity and mortality. The limited selections of drug treatment are not able to control the progress of disease in people with active and persistent HBV infection. Immunotherapy to control the degree of viral infection is one possible alternative solution to this challenge. HBV DNA vaccines, with their strong ability to induce cell-mediated immune responses, offer an attractive option. HBV surface protein is important in viral immunity. Re-establishing anti-S immunity in chronic HBV infected patients will bring significant benefit to the patients. Previous studies have shown that HBV S DNA vaccines are immunogenic in a number of animal studies. In the current study, we further investigated the effect of glycosylation to the expression and immunogenicity of S DNA vaccines. Our results demonstrate that deglycosylation at the two potential N-linked glycosylation sites in S protein resulted in a significant decrease of S-specific cell-mediated immune responses, but did not affect anti-S antibody responses. This finding provides important direction to the development of S DNA vaccines to elicit the optimal and balanced antibody and cell-mediated immune responses to treat people with HBV chronic infections.

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    • "Gamma interferon (IFN-γ) and interleukin 4 (IL-4) ELISPOT assays were performed to detect the HBs peptide-specific T cell responses in mouse splenocytes, as previously described [27], [35]. Mouse IFN-γ kit (U-CyTech Biosciences, Netherlands) and IL-4 ELISPOT kit (U-CyTech Biosciences, Netherlands) were used to detect HBs-specific IFN-γ and IL-4 T cell responses, according to manufacturers' directions. "
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    PLoS ONE 07/2012; 7(7):e41573. DOI:10.1371/journal.pone.0041573 · 3.23 Impact Factor
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    • "Additional studies were conducted to ask if glycosylation of HA has been affected with the use of a different leader sequence which may influence the immune responses. Our previous study with a hepatitis B surface antigen suggested that post-translational modifications including glycosylation may affect the immunogenicity of DNA vaccine delivered antigens [23]. The Asn (N)-linked glycosylation of influenza HA proteins are essential for virus infectivity and vaccine immunogenicity [24], [25]. "
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    PLoS ONE 12/2011; 6(12):e28757. DOI:10.1371/journal.pone.0028757 · 3.23 Impact Factor
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    • "Many studies on the expression of rabies virus glycoprotein (G) in different expression systems and the evaluation of immunogenicity of this protein in animal models show that glycosylation may be essential for the function of rabies virus G protein (Wunner et al., 1983; Yelverton et al., 1983; Kieny et al., 1984; Wiktor et al., 1984; Prehaud et al., 1989). Glycosylation of hepatitis B surface (HBS) antigen is also necessary (Xing et al., 2008). In the later study, authors investigated the effect of deglycosylation on the immunogenicity of HBS antigen and showed that deglycosylation of S protein resulted in a significant decrease in S-specific cellmediated immune responses in mice. "
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