E. coli Heat-labile Enterotoxin B Subunit as a Platform for the Delivery of HIV Gag p24 Antigen.

Karmarcha Martin,Toufic O Nashar

doi:10.4172/2155-9899.1000140

Abstract

Multiple vaccination strategies have been devised against HIV-1 including delivery of HIV moieties in attenuated or replication defective recombinant microbial agents alone or in combination with priming agents in form of soluble proteins or naked DNA. For the priming agents to be effective, adjuvants might be essential in directing the immune response to a desired outcome. E. coli enterotoxin B subunit (LTB) is an effective adjuvant and carrier for other proteins and epitopes. Here we show that conjugation of HIV gag p24 to LTB enhances the T cell response to gag p24 by increasing rate of T cell division compared to other treatments. Because HIV vaccines are likely to be multivalent, we further investigated whether gag p24 inhibits antigen presentation of an unrelated antigen, OVA. Addition of gag p24 to OVA-responsive DO.11.10 cell culture did not have adverse effects on antigen presentation. Interestingly, the presence of LTB in these cultures significantly increased proliferation of DO.11.10 cells. In all, the results suggest the use of LTB to boost immune responses against HIV gag p24 in systemic priming regimens with oral recombinant HIV vaccines.

Highlights

A number of different strategies are sought in the fight against the Human Immunodeficiency Virus- 1 (HIV-1)
We previously demonstrated that the B subunits of Escherichia coli enterotoxin (LTB) increase expression of stimulatory and accessory proteins on antigen presenting cells (APC), including, MHC class II, B7-2, CD25, and ICAM-1, and result in increased CD4+ T-cell activation [18,19,20,21]
We show that conjugation of HIV gag p24 to LTB enhances the T cell response by increasing rate of cell division compared to other treatments

Summary

Introduction

A number of different strategies are sought in the fight against the Human Immunodeficiency Virus- 1 (HIV-1). Most of these are directed to deliver and stimulate immune responses to HIV moieties expressed by recombinant viruses or bacteria [1,2,3,4,5]. We have recently shown that recombinant coxsakievirus expressing a 73 aa sequence of HIV gag p24, induced high level of T cell responses [6]. Among the systemic priming agents are DNA expressing HIV proteins, HIV gag p24 targeted by antibody to antigen presenting cells (APC), and HIV gag p24-Fc fusion protein [1,7,8].

Methods

Results

Conclusion