Adjuvant Activity of a Nontoxic Mutant of<i>Escherichia coli</i>Heat-Labile Enterotoxin on Systemic and Mucosal Immune Responses Elicited against a Heterologous Antigen Carried by a Live<i>Salmonella enterica</i>Serovar Typhimurium Vaccine Strain

Guillobel, Heloísa Carneiro da Rocha; Carinhanha, Joana Iabrudi; Cárdenas, L; Clements, John D.; Almeida, Darcy Fontoura de; Ferreira, Luís Carlos de Souza

doi:10.1128/iai.68.7.4349-4353.2000

Cited by 33 publications

(18 citation statements)

References 32 publications

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“…Derivatives of CT and LT have been explored as adjuvants in the development of Helicobacter pylori vaccines (24). Previous studies have also shown that immune responses to a bivalent Salmonella vaccine expressing the ETEC colonization factor CFA/I were enhanced by the coadministration of a mutant LT that was used as a mucosal adjuvant (16).…”

Section: Discussionmentioning

confidence: 99%

Concomitant EnterotoxigenicEscherichia coliInfection Induces Increased Immune Responses toVibrio choleraeO1 Antigens in Patients with Cholera in Bangladesh

et al. 2010

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Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC) are major bacterial pathogens that cause dehydrating disease requiring hospitalization of children and adults. The cholera toxin (CT) produced by V. cholerae O1 and the heat-labile toxin (LT) and/or heat-stable toxin (ST) of ETEC are responsible for secretory diarrhea. We have observed that about 13% of hospitalized diarrheal patients are concomitantly infected with V. cholerae O1 and ETEC. In order to understand the outcome of such dual infections on the clinical and immunological responses in cholera patients, we studied patients infected with V. cholerae O1 (group VC; n ‫؍‬ 25), those infected with both V. cholerae O1 and ETEC (group VCET; n ‫؍‬ 25), and those infected with ETEC only (group ET; n ‫؍‬ 25). The VCET group showed more severe dehydration and had a higher intake of intravenous fluid and more vomiting than the ETEC group (P ‫؍‬ 0.01 to 0.003). The VCET patients showed higher vibriocidal responses and increased antibody titers to cholera toxin and lipopolysaccharide (LPS) in plasma than did the V. cholerae O1 patients (P ‫؍‬ 0.02 to <0.001). All responses in the V. cholerae O1 and in the VCET groups were more robust than those seen in the group infected with ETEC only (P ‫؍‬ 0.01 to <0.001). We thus show that concomitant colonization with ETEC induces immune responses to V. cholerae antigens that are more robust than those seen with V. cholerae O1 infection alone. It is possible that LT or other factors expressed by ETEC may play a role as a mucosal adjuvant in enhancing the immune responses to V. cholerae O1.Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC) are two major bacterial pathogens responsible for community-based infections and hospitalizations of both adults and children. Cholera and ETEC diarrhea together may account for nearly 50% of the million or so cases of diarrhea occurring annually in Bangladesh (11,37). The pathogenesis of disease caused by V. cholerae O1 and that of disease caused by ETEC are similar. The cholera toxin (CT) produced by V. cholerae O1 and the heat-labile enterotoxin (LT) of ETEC share 80% identity at the nucleotide level (39). LT produced by ETEC is structurally, functionally, and immunologically very similar to CT produced by Vibrio cholerae. Each toxin consists of a toxin A subunit that shares 75% homology with each other (CTA and LTA, respectively), which is noncovalently associated with five identical B subunits (CTB and LTB, respectively) (43). LTB and CTB also show a high degree of homology to each other, with an 85% conservation of amino acids in the mature proteins. There is evidence from crystallographic studies that LTB and CTB pentamers are also structurally similar (25,41,42). There has been a high degree of immunological cross-reactivity between these proteins reported by many investigators, with both shared and unique epitopes (45); the majority of antibodies are directed against epitopes on the assembled pentamers. Both V. cholerae and ETEC share similar type II secretion s...

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Section: Discussionmentioning

confidence: 99%

Concomitant EnterotoxigenicEscherichia coliInfection Induces Increased Immune Responses toVibrio choleraeO1 Antigens in Patients with Cholera in Bangladesh

et al. 2010

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“…LT and cholera toxin are the most potent and deeply studied mucosal adjuvants described thus far (44). LT enhances secreted and systemic antibody responses to coadministered soluble or particulate antigens, such as live Salmonella cells, delivered via the oral route (19). In an attempt to enhance flagellin immunogenicity relative to its ability to induce secreted and systemic antibody responses, we orally or nasally immunized BALB/c mice with three doses of live ICB5 strain coadministered with LT R192G , a nontoxic LT derivative with preserved immunomodulatory properties (11).…”

Section: Resultsmentioning

confidence: 99%

“…The discovery of mucosal adjuvants, such as the cholera or heat-labile toxins, has led to a renewed interest in the development of effective oral vaccines based either on acellular formulations or whole live or inactivated microorganisms (11,19,44). In the present work, the incorporation of LT R192G , an LT derivative with reduced toxic effects but preserved adjuvant effects, did not enhance type d flagellin immunogenicity with regard to the production of systemic and secreted antibody responses in mice immunized via mucosal routes with flagellated S. enterica serovar Dublin strains.…”

Section: Discussionmentioning

confidence: 99%

Host and Bacterial Factors Affecting Induction of Immune Responses to Flagellin Expressed by AttenuatedSalmonellaVaccine Strains

Sbrogio-Almeida

Mosca

Massis³

et al. 2004

Infect Immun

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“…Various approaches or a combination of approaches can be examined to overcome the observed partial humoral response with the MASC-13 oral spore vaccine; these approaches include (i) generation of a strain expressing higher levels of PA through utilization of promoters that are much more potent than ␣-amylase (23), (ii) coadministration with mucosal adjuvants (5,25), (iii) engineering the spores with M cells targeting molecules that potentially improve the uptake of the spores by M cells (4,28), and (iv) development of strains which are able to persist longer in phagocytic cells (18).…”

Section: Discussionmentioning

confidence: 99%

Oral Spore Vaccine Based on Live Attenuated Nontoxinogenic Bacillus anthracis Expressing Recombinant Mutant Protective Antigen

Aloni-Grinstein¹,

Gat²,

Altboum

et al. 2005

Infect Immun

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An attenuated nontoxinogenic nonencapsulated Bacillus anthracis spore vaccine expressing high levels of recombinant mutant protective antigen (PA), which upon subcutaneous immunization provided protection against a lethal B. anthracis challenge, was found to have the potential to serve also as an oral vaccine. Guinea pigs immunized per os with the recombinant spore vaccine were primed to B. anthracis vegetative antigens as well as to PA, yet only a fraction of the animals (30% to 50%) mounted a humoral response to all of these antigens. Protective immunity provided by per os immunization correlated with a threshold level of PA neutralizing antibody titers and was long-lasting. Protection conferred by per os immunization was attained when the vaccine was administered in the sporogenic form, which, unlike the vegetative cells, Anthrax is an acute infectious disease caused by the sporeforming bacterium Bacillus anthracis. Three disease forms are recognized in humans, depending on the route by which spores enter the body; these three forms are the cutaneous form (via skin infection), the pulmonary form (via airborne inhalation), and the gastrointestinal form (via ingestion of contaminated food) (29). Fatal inhalational anthrax was a major concern during the recent deliberate B. anthracis spore dispersal events (38), which emphasized the need to focus on providing local immune protection at the mucosal sites of invasion in addition to systemic protection.The major B. anthracis virulence factors are encoded by two plasmids, pXO2, which carries the genes directing the synthesis of the poly-D-glutamic acid capsule, and pXO1, which encodes the two binary exotoxins, the lethal toxin (LT) and the edema toxin (51, 52). The two toxins have a common cell receptorbinding component, the protective antigen (PA), which interacts with the lethal factor (LF) and the edema factor (EF) to form LT and edema toxin, respectively. After binding to the cell receptor, PA mediates the translocation of LF and EF into the cytosol, where they have their detrimental activities. PA has an essential role in the induction of immunity and protection against the disease, and vaccination with PA alone can induce protective immunity (2, 21, 65). There is a direct relationship between the amount of PA administered to experimental animals and the extent of the humoral immune response elicited against PA (11,39,40,43,58,65). PA neutralizing antibody titers, measured by in vitro protection of macrophage cell lines from toxicity by LT, were shown to correlate with the in vivo protective immunity (58).Two PA-based acellular vaccine formulations have been licensed for human use, one in the United States and one in the United Kingdom. Both consist mainly of PA from cultures of nonencapsulated, toxin-producing B. anthracis strains, and they are adsorbed onto aluminum hydroxide gel and alum precipitated, respectively (32, 46). The United States vaccine is administered subcutaneously (s.c.) (13), and the United Kingdom vaccine is given intramuscularly (anthrax v...

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Adjuvant Activity of a Nontoxic Mutant ofEscherichia coliHeat-Labile Enterotoxin on Systemic and Mucosal Immune Responses Elicited against a Heterologous Antigen Carried by a LiveSalmonella entericaSerovar Typhimurium Vaccine Strain

Cited by 33 publications

References 32 publications

Concomitant EnterotoxigenicEscherichia coliInfection Induces Increased Immune Responses toVibrio choleraeO1 Antigens in Patients with Cholera in Bangladesh

Concomitant EnterotoxigenicEscherichia coliInfection Induces Increased Immune Responses toVibrio choleraeO1 Antigens in Patients with Cholera in Bangladesh

Host and Bacterial Factors Affecting Induction of Immune Responses to Flagellin Expressed by AttenuatedSalmonellaVaccine Strains

Oral Spore Vaccine Based on Live Attenuated Nontoxinogenic Bacillus anthracis Expressing Recombinant Mutant Protective Antigen

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