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Infection and Immunity, March 2001, p. 1605-1612, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1605-1612.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Intranasal Immunization with SAG1 and Nontoxic Mutant Heat-Labile Enterotoxins Protects Mice against Toxoplasma gondii

C. Bonenfant,1 I. Dimier-Poisson,1 F. Velge-Roussel,1 D. Buzoni-Gatel,1 G. Del Giudice,2 R. Rappuoli,2 and D. Bout1,*

Faculté des Sciences Pharmaceutiques, UMR Université---INRA d'Immunologie Parasitaire, 37200 Tours, France,1 and IRIS Research Center, Chiron Spa, 53100 Siena, Italy2

Received 25 September 2000/Returned for modification 14 November 2000/Accepted 20 December 2000

Effective protection against intestinal pathogens requires both mucosal and systemic immune responses. Intranasal administration of antigens induces these responses but generally fails to trigger a strong protective immunity. Mucosal adjuvants can significantly enhance the immunogenicities of intranasally administered antigens. Cholera toxin (CT) and heat-labile enterotoxin (LT) are strong mucosal adjuvants with a variety of antigens. Moreover, the toxicities of CT and LT do not permit their use in humans. Two nontoxic mutant LTs, LTR72 and LTK63, were tested with Toxoplasma gondii SAG1 protein in intranasal vaccination of CBA/J mice. Vaccination with SAG1 plus LTR72 or LTK63 induced strong systemic (immunoglobulin G [IgG]) and mucosal (IgA) humoral responses. Splenocytes and mesenteric lymph node cells from mice immunized with LTR72 plus SAG1, but not those from mice immunized with LTK63 plus SAG1, responded to restimulation with a T. gondii lysate antigen in vitro. Gamma interferon and interleukin 2 (IL-2) production by splenocytes and IL-2 production by mesenteric lymph node cells were observed in vitro after antigen restimulation, underlying a Th1-like response. High-level protection as assessed by the decreased load of cerebral cysts after a challenge with the 76K strain of T. gondii was obtained in the group immunized with LTR72 plus SAG1 and LTK63 plus SAG1. They were as well protected as the mice immunized with the antigen plus native toxins. This is the first report showing protection against a parasite by using combinations of nontoxic mutant LTs and SAG1 antigen. These nontoxic mutant LTs are now attractive candidates for the development of mucosally delivered vaccines.

* Corresponding author. Mailing address: UMR Université-INRA d'immunologie parasitaire, Faculté des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France. Phone: 33 247 36 71 85. Fax: 33 247 36 72 52. E-mail: bout{at}univ-tours.fr.

Infection and Immunity, March 2001, p. 1605-1612, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1605-1612.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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