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.
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 Thl 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.
Mrsny
R J
RJ
Department of Pharmaceutical Research and Development, Genetech Inc., South San Francisco, CA 94080-4990, USA. mrsny@gene.com
Daugherty
A L
AL
Fryling
C M
CM
FitzGerald
D J
DJ
D036002:ADP Ribose Transferases; D016915:AIDS Vaccines / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D001427:Bacterial Toxins; D005098:Exotoxins / Q000235:genetics* / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis*; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D012463:Saliva / Q000276:immunology*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D005098:Exotoxins; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C059762:HIV envelope protein gp120 (305-321)