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

We have used a mouse immunization model to evaluate the potential for a chi mera 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 I b region of ntPE. Following either vaginal, rectal, oral or subcutaneous ad ministration and boosting, anti-gp120-specific IgA and IgG levels in serum and saliva samples were assessed by ELISA. All dosing regimens stimulated s ignificant 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. Isotypi ng of serum antibodies at this time suggested that both a Th1 and a Th2 res ponse had been induced. Responses to ntPE-V3MN26 following subcutaneous inj ection in the presence or absence of Freund's adjuvant demonstrated that Fr eund's adjuvant resulted in a three-fold greater enhancement of immune resp onse compared to administration of chimera alone. These results demonstrate that mucosal presentation of a chimera composed of a nontoxic form of Pseu domonas exotoxin can result in a strong mucosal and systemic antigen-specif ic immune response to an integrated antigen. The profound memory responses induced by this chimera may be particularly useful for practical vaccine ap plications. (C) 1999 Elsevier Science Ltd. All rights reserved.