Enhancement of humoral immune responses to HBsAg by heat shock protein gp96 and its N-terminal fragment in mice

Abstract

gp96 or its N-terminal fragment greatly improved humoral immune response induced by HBsAg, but failed to enhance the CTL response, which demonstrated the potential of using gp96 or its N-terminal fragment as a possible adjuvant to augment humoral immune response against HBV infection.

Glycoprotein 96-Mediated Presentation of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Human Leukocyte Antigen Class I-Restricted Peptide and Humoral Immune Responses to HIV-1 p24

“…Most studies so far on the immune effect of gp96 focused mainly on its enhancement of CTLs; recently, several studies clearly demonstrated the potential of using gp96 or its Nterminal fragment as an adjuvant to augment the humoral immunity to hepatitis B virus (18) and human papillomavirus type 16 infection (8). However, whether normal tissue-derived gp96 could influence humoral immune response to HIV-1 p24 has not been fully addressed.…”

“…Previous studies in virus and parasite model systems have focused on the use of codelivery of viral protein or DNA antigen with gp96 or its N-terminal fragment without covalent linkage (8,18). In this study, we established the N-terminal fragment of gp96 fusion protein (HIV-1 p24-N336).…”

“…In this study, we evaluated the humoral adjuvant effect of gp96 and its N-terminal fragment using Gag-p24 instead of the small 10-mer peptide. It is possible that gp96 acts as an adjuvant, which may stimulate the humoral immune response to an antigen mixed with gp96 (18). Mice were injected with 4 g of p24 mixed with 6 g of gp96 or N336, and the anti-HIV-1 p24 antibody titer was measured.…”

Comparison of adjuvant activity of N- and C-terminal domain of gp96 in a Her2-positive breast cancer model

“…Our previous experiments demonstrated that fusion, but not co-administration, of the gp96 C-terminal domain to Her2/neu led to improved inhibition of tumor growth (Pakravan et al 2010a). Previously, it was demonstrated that the gp96 N-terminal domain has potent adjuvant activity toward hepatitis B surface antigen (HBsAg; Li et al 2005b;Yan et al 2007). In this study, the adjuvant activity of gp96 N-and the Cterminal domain was compared in a Her2 breast cancer model.…”

Mini-chaperones

“…41 Most studies on the immune effect of gp96 were focused on knowing whether the recombinant N-terminal fragment of gp96 (NT-gp96, amino acid 22-355) expressed in E. coli can stimulate the immune system similar to native gp96 isolated from livers of normal BALB/c mice. 72 Thus, in an experiment, mice groups received one of the following regimens subcutaneously including native gp96; NT-gp96; HBsAg; HBsAg + gp96; HBsAg + NT-gp96; HBsAg + incomplete Freud's adjuvant and HBsAg + NT-gp96 (95°C heated for 30 min). The results demonstrated that native gp96 or NT-gp96 greatly improved humoral immune response induced by HBsAg, but failed to increase the CTL response.…”