Peripheral blood antibody-secreting cells in the evaluation of the immune response to an oral vaccine

Kantele, Anu

doi:10.1016/0168-1656(95)00134-4

Cited by 30 publications

(30 citation statements)

References 32 publications

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“…These kinetics are similar to those reported after oral immunization strategies for enteric pathogens, even when multiple doses are given, and are also similar to ASC kinetics after intranasal immunizations with live, attenuated influenza vaccines (15)(16)(17)(18)(19)26). Reports of ASC responses to sequential mucosal doses of nonliving antigens are infrequent, but multiple oral doses of killed Salmonella enterica serovar Typhi Ty21a also appear to yield only a single wave of ASCs (17).…”

Section: Discussionsupporting

confidence: 61%

“…In this view, serum antibodies may be surrogate markers for multiple protective mechanisms operating at intestinal mucosal sites (12,29,33,34). Measurement of specific antibody-secreting cells (ASCs), especially those producing immunoglobulin A (IgA) antibodies and transiting the peripheral blood to mucosal sites 6 to 10 days after infection or immunization, and/or measurement of antibodies in mucosal secretions has been proposed as a more predictive marker of mucosal vaccine-induced protection (15,19).…”

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confidence: 99%

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Safety and Immunogenicity of a Proteosome- Shigella flexneri 2a Lipopolysaccharide Vaccine Administered Intranasally to Healthy Adults

et al. 2001

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We studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S. flexneri 2a lipopolysaccharide (LPS) complexed to meningococcal outer membrane proteins-proteosomes-in normal, healthy adults. A two-dose series of immunizations was given by intranasal spray, and doses of 0.1, 0.4, 1.0, and 1.5 mg (based on protein) were studied in a dose-escalating design. The vaccine was generally well tolerated. The most common reactions included rhinorrhea and nasal stuffiness, which were clearly dose related (P < 0.05). These reactions were self-limited and generally mild. The vaccine elicited S. flexneri 2a LPS-specific immunoglobulin A (IgA), IgG, and IgM antibody-secreting cells (ASCs) in a dose-responsive manner. At doses of 1.0 or 1.5 mg, highly significant (P < 0.001) increases in ASCs of all antibody isotypes occurred and 95% of subjects had an ASC response in at least one antibody isotype. Dose-related serum antibody responses were observed, with geometric mean two-to fivefold rises in specific serum IgA and IgG titers and two-to threefold rises in IgM in the 1.0-and 1.5-mg-dose groups (P < 0.0001 for each isotype). Elevated serum antibody levels persisted through day 70. Increases in fecal IgG and IgA and also in urinary IgA specific for S. flexneri 2a LPS were demonstrated. These were most consistent and approached statistical significance (P ‫؍‬ 0.02 to 0.12 for various measures) on day 70 after the first dose. The magnitude of immune responses to intranasally administered proteosome-S. flexneri 2a LPS vaccine is similar to those reported for live vaccine candidates associated with protective efficacy in human challenge models, and further evaluation of this product is warranted.

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Section: Discussionsupporting

confidence: 61%

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confidence: 99%

Safety and Immunogenicity of a Proteosome- Shigella flexneri 2a Lipopolysaccharide Vaccine Administered Intranasally to Healthy Adults

et al. 2001

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“…Activated mucosal lymphocytes migrate from intestinal tissue and circulate within peripheral blood before rehoming to mucosal tissues (20,31). This migration peaks 1 to 2 weeks after intestinal infection and may be measured by using peripheral blood mononuclear cells (PBMC) in an antibody-secreting cell (ASC) assay (19,26) or in supernatants recovered from harvested PBMC (the "antibody in lymphocyte supernatant" [ALS] assay) (7,31). Although ALS and ASC responses have previously been measured after immunization with oral live attenuated typhoid vaccines, detailed analyses of ALS or ASC responses in individuals with wild-type typhoid fever are lacking (21,24).…”

mentioning

confidence: 99%

Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever

Sheikh

Bhuiyan

Khanam

et al. 2009

Clin Vaccine Immunol

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Many currently available diagnostic tests for typhoid fever lack sensitivity and/or specificity, especially in areas of the world where the disease is endemic. In order to identify a diagnostic test that better correlates with typhoid fever, we evaluated immune responses to Salmonella enterica serovar Typhi (serovar Typhi) in individuals with suspected typhoid fever in Dhaka, Bangladesh. We enrolled 112 individuals with suspected typhoid fever, cultured day 0 blood for serovar Typhi organisms, and performed Widal assays on days 0, 5, and 20. We harvested peripheral blood lymphocytes and analyzed antibody levels in supernatants collected on days 0, 5, and 20 (using an antibody-in-lymphocyte-supernatant [ALS] assay), as well as in plasma on these days. We measured ALS reactivity to a serovar Typhi membrane preparation (MP), a formalin-inactivated whole-cell preparation, and serovar Typhi lipopolysaccharide. We measured responses in healthy Bangladeshi, as well as in Bangladeshi febrile patients with confirmed dengue fever or leptospirosis. We categorized suspected typhoid fever individuals into different groups (groups I to V) based on blood culture results, Widal titer, and clinical features. Responses to MP antigen in the immunoglobulin A isotype were detectable at the time of presentation in the plasma of 81% of patients. The ALS assay, however, tested positive in all patients with documented or highly suspicious typhoid, suggesting that such a response could be the basis of improved diagnostic pointof-care-assay for serovar Typhi infection. It can be important for use in epidemiological studies, as well as in difficult cases involving fevers of unknown origin.Salmonella enterica serovar Typhi (serovar Typhi) is the cause of typhoid fever, an illness that affects over 20,000,000 individuals worldwide each year, killing over 200, 000 (5, 8, 16). The largest burden of typhoid fever is borne by impoverished individuals in resource-poor areas of the world. Serovar Typhi is a human-restricted invasive enteric pathogen which, after ingestion, crosses the intestinal mucosa, is taken up by gutassociated lymphoreticular tissues, and enters the systemic circulation. Both mucosal and systemic host immune responses are stimulated after infection. Serovar Typhi is an intracellular pathogen, and antibody and cell-mediated immune responses occur after infection or immunization with live oral attenuated typhoid vaccines (10,25,34).Diagnostic tests for typhoid fever often lack sensitivity and/or specificity, especially in areas of the world that are endemic for typhoid fever, where clinically distinguishing typhoid fever from other febrile illnesses is difficult (5, 17, 39). Microbiologic culturing of blood is approximately 30 to 70% sensitive, with the highest sensitivity being associated with an absence of prior use of antibiotics and the culturing of larger volumes of blood, features that complicate this mode of diagnosis in young children (5,6,8,36). Microbiologic culturing of bone marrow aspirates is more sensitive than bl...

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“…This difference in isotype distribution combined with the significantly lower responses observed in children accounts for the fact that the absolute numbers of IgM-ASC did not differ statistically between adults and children, even if a significant difference was found in the total response (IgA-plus IgG-plus IgM-ASC) (P Ͻ 0.003) as well as in IgA-and IgG-ASC responses (P Ͻ 0.003 and P Ͻ 0.002, respectively). In adults, the low IgM-ASC response appears to be a typical feature of the urinary tract (18), since the IgM-ASC response has been shown to be almost as prominent as the IgA-ASC response in adults when the antigen is administered via another mucosal surface, the gastrointestinal tract (13)(14)(15), even after booster immunization (16). Earlier studies have suggested that IgM might have only a minor role in the local immune system of the urinary tract (10), as IgM is rarely, if ever, present in the urine of healthy humans (8).…”

Section: Discussionmentioning

confidence: 99%

“…The difficulty of getting acute-phase samples at comparable stages of the disease (because the onset of symptoms varies and patients seek medical care after various times) was solved by taking two "acute-phase" samples. In order to catch the peak (or near the peak) of the ASC response, which according to our studies on oral vaccines (13,14) is expected 7 days after antigen exposure, the sampling was carried out as follows. The acute-phase I specimens were collected 1 to 3 days after admission to the hospital, acute-phase II specimens were collected 1 week later, and convalescentphase samples were collected 3 to 7 weeks after the onset of the disease.…”

Section: Methodsmentioning

confidence: 99%

Local Immune Response to Upper Urinary Tract Infections in Children

Palkola

Arvilommi²,

Honkinen

et al. 2008

Clin Vaccine Immunol

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Vaccines are needed against urinary tract infections (UTIs) in children, as episodes of pyelonephritis (PN) may cause renal scarring. Local immune mechanisms are regarded to confer protection, yet they have been poorly characterized for children. This study explores the local immune response in children by looking for newly activated pathogen-specific antibody-secreting cells (ASC), expected to appear transiently in the circulation as a response to UTI. Urinary tract-originating ASC specific to each patient's own pathogen or P fimbria were studied in 37 children with PN. The children were examined for recidivism and renal scarring in a 6-month follow-up study. Pathogen-specific ASC were found in 33/37 children, with the magnitude increasing with age. In contrast to the case for adults, with immunoglobulin A (IgA) dominance, in 18/33 cases IgM dominated the response, and this occurred more frequently in infants (63%) than in older children (30%). The most vigorous response was found to whole Escherichia coli bacteria (geometric mean, 63 ؎ 2,135 ASC/10 6 peripheral blood mononuclear cells [PBMC]), yet responses were found to P fimbriae (13 ؎ 33 ASC/10 6 PBMC), too. The response peaked at 1 to 2 weeks and was low/negligible 3 to 7 weeks after the beginning of symptoms. Recidivism was seen in seven patients, and renal scarring was seen in nine patients. In conclusion, a response of circulating ASC was found in children with UTIs, with the magnitude increasing with age. Since IgM is not present in urine, the IgM dominance of the response suggests that systemic immune mechanisms are more important in the immune defense in children than in adults. In 81% of patients, no recidivism was seen, suggesting a successful immune defense.Urinary tract infection (UTI) represents one of the most common infections encountered in the practice of pediatrics today; UTIs comprise a severe problem, since renal scarring occurs in up to 20% of children with acute pyelonephritis (PN) (4, 11) and can result in an impairment of renal function. A vaccine against UTI is needed. Thorough knowledge of the immune mechanisms involved in protection would be beneficial in the development of effective vaccines.UTIs are mostly of the ascending type, and therefore, the first defense line the pathogen encounters is the local immune system on the mucosa of the urinary tract, especially urinary antibodies. It has been shown that local antibodies can bind to the infecting bacteria and prevent their adherence to mucosal surfaces (29,31,33,34) and the following infection. Accordingly, in animal experiments, local immunization eliciting local antibodies has been shown to protect against disease (36, 37). Recently, in adults, a vaginally administered vaccine has proven to be protective against reinfections in phase II trials (9, 35). If a urinary pathogen is able to cross the mucosal barrier, it must be cleared by the systemic immune mechanisms. It appears that an optimal defense state would involve both local and systemic immunity. The fact that 75% of previ...

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Peripheral blood antibody-secreting cells in the evaluation of the immune response to an oral vaccine

Cited by 30 publications

References 32 publications

Safety and Immunogenicity of a Proteosome- Shigella flexneri 2a Lipopolysaccharide Vaccine Administered Intranasally to Healthy Adults

Safety and Immunogenicity of a Proteosome- Shigella flexneri 2a Lipopolysaccharide Vaccine Administered Intranasally to Healthy Adults

Salmonella enterica Serovar Typhi-Specific Immunoglobulin A Antibody Responses in Plasma and Antibody in Lymphocyte Supernatant Specimens in Bangladeshi Patients with Suspected Typhoid Fever

Local Immune Response to Upper Urinary Tract Infections in Children

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