Mucosal administration of a chimera composed of Pseudomonas exotoxin and the gp120 V3 loop sequence of HIV-1 induces both salivary and serum antibodyresponses
Rj. Mrsny et al., Mucosal administration of a chimera composed of Pseudomonas exotoxin and the gp120 V3 loop sequence of HIV-1 induces both salivary and serum antibodyresponses, VACCINE, 17(11-12), 1999, pp. 1425-1433
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.