Mucosal administration of a chimera composed of Pseudomonas exotoxin and the gp120 V3 loop sequence of HIV-1 induces both salivary and serum antibody responses

Abstract

We have used a mouse immunization model to evaluate the potential for a chimera protein composed of a nontoxic form of Pseudomonas exotoxin (ntPE) to incite and sustain a mucosal immune response against an integrated antigen. The chimera, termed ntPE-V3MN26, contained 26 amino acids of the gp120 V3 loop region sequence of the MN strain of HIV-1 integrated in place of the Ib region of ntPE. Following either vaginal, rectal, oral or subcutaneous administration and boosting, anti-gp120-specific IgA and IgG levels in serum and saliva samples were assessed by ELISA. All dosing regimens stimulated significant and comparable salivary IgA and serum IgG responses at 1, 2 and 3 months after the initial inoculation. Following a boost at 16 months with ntPE-V3MN26, a strong memory response to the antigen was observed. Isotyping of serum antibodies at this time suggested that both a Th1 and a Th2 response had been induced. Responses to ntPE-V3MN26 following subcutaneous injection in the presence or absence of Freund's adjuvant demonstrated that Freund's adjuvant resulted in a three-fold greater enhancement of immune response compared to administration of chimera alone. These results demonstrate that mucosal presentation of a chimera composed of a nontoxic form of Pseudomonas exotoxin can result in a strong mucosal and systemic antigen-specific immune response to an integrated antigen. The profound memory responses induced by this chimera may be particularly useful for practical vaccine applications.