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Infection and Immunity, February 1999, p. 826-833, Vol. 67, No. 2
Department of Microbiology and Immunology,
Tulane University Medical Center, New Orleans, Louisiana 70112
Received 13 August 1998/Returned for modification 11 September
1998/Accepted 13 November 1998
The incidence of fungal infections caused by the opportunistic
yeast Candida albicans has increased significantly in
recent years. The ability to vaccinate selected patients against the organism would be advantageous. In this paper we describe a potential anti-C. albicans vaccine consisting of heat-killed C. albicans (HK-CA) in combination with the novel mucosal adjuvant
LT(R192G), a genetically detoxified form of the heat-labile toxin of
enterotoxigenic Escherichia coli. Groups of male CBA/J mice
were immunized intranasally on three occasions at weekly intervals with
2 × 107 HK-CA per dose, alone or in conjunction with
10 µg of LT(R192G) per dose. Two weeks following the last application
of antigen, some animals were challenged intravenously (i.v.) with
104, 105, or 106 viable C. albicans to assess protection as measured by survival and/or
culture. Some groups of animals were footpad tested with C. albicans mannan to assess delayed-type hypersensitivity
(DTH), and all the animals were bled for antibody assays. In two
independent studies, all the animals immunized with HK-CA plus
LT(R192G) were able to eradicate 104 C. albicans completely, as determined by kidney culture 4 weeks after challenge. Animals immunized with HK-CA only had reduced levels
of C. albicans compared to the adjuvant or
saline-only control. Greatly enhanced survival was observed when mice
immunized with HK-CA plus LT(R192G) were challenged with
105 live C. albicans as well. Animals immunized
with HK-CA plus LT(R192G) developed a significant DH response,
while those given HK-CA alone developed only marginal DH responses.
High immunoglobulin G (IgG) levels to cytoplasmic antigens developed in
mice immunized with HK-CA plus LT(R192G), but they were found only
after i.v. challenge. Addition of adjuvant shifted the antibody
isotype production in i.v.-challenged animals to a response
dominated by IgG2a. Clearly, intranasal immunization with killed
C. albicans in conjunction with LT(R192G) afforded
significant levels of protection. This novel approach offers new
possibilities for the development of an effective vaccine against
candidiasis for use in humans.
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Effectiveness of a Vaccine Composed of Heat-Killed
Candida albicans and a Novel Mucosal Adjuvant, LT(R192G),
against Systemic Candidiasis
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, Tulane University Medical Center, 1430 Tulane Ave., New Orleans, LA 70112. Phone: (504) 587-2171. Fax: (504) 588-5144. E-mail: lfreyta{at}mailhost.tcs.tulane.edu.
Infection and Immunity, February 1999, p. 826-833, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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