Identification of Three Highly Attenuated Salmonella typhimurium Mutants That Are More Immunogenic and Protective in Mice than a Prototypical aroA Mutant

ABSTRACT A panel of Salmonella typhimurium 14028s mutants, which were previously shown to be highly attenuated in the BALB/c mouse model of infection, were analyzed for their potential as liveSalmonella oral-vaccine candidates. A prototypicalaroA mutant was chosen as a basis of comparison. From the panel of mutants initially chosen for this study, three mutants with comparable levels of attenuation elicited higherSalmonella-specific serum immunoglobulin G (IgG) and/or mucosal secretory-IgA antibody titers than the aroA vaccine strain. The three mutants, CL288, CL401, and CL554, also elicited a better protective immune response than the aroA control strain, after a single oral dose of 1 × 109 to 2 × 109 bacteria.

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Mimicking Native Display of CD0873 on Liposomes Augments Its Potency as an Oral Vaccine against Clostridioides difficile

Vaccines ◽

10.3390/vaccines9121453 ◽

2021 ◽

Vol 9 (12) ◽

pp. 1453

Author(s):

Cansu Karyal ◽

Panayiota Palazi ◽

Jaime Hughes ◽

Rhys C. Griffiths ◽

Ruby R. Persaud ◽

...

Keyword(s):

Oral Vaccine ◽

Secretory Iga ◽

Great Promise ◽

Vaccine Platform ◽

Neutralising Antibodies ◽

Partial Protection ◽

Mucosal Vaccination ◽

Clostridioides Difficile ◽

Specific Serum ◽

Clostridioides Difficile Infection

Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally to hamsters induces neutralising antibodies locally as well as systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was to determine whether displaying CD0873 on liposomes, mimicking native presentation, would drive a stronger antibody response. The recombinant form we previously tested resembles the naturally cleaved lipoprotein commencing with a cysteine but lacking lipid modification. A synthetic lipid (DHPPA-Mal) was designed for conjugation of this protein via its N-terminal cysteine to the maleimide headgroup. DHPPA-Mal was first formulated with liposomes to produce MalLipo; then, CD0873 was conjugated to headgroups protruding from the outer envelope to generate CD0873-MalLipo. The immunogenicity of CD0873-MalLipo was compared to CD0873 in hamsters. Intestinal sIgA and CD0873-specific serum IgG were induced in all vaccinated animals; however, neutralising activity was greatest for the CD0873-MalLipo group. Our data hold great promise for development of a novel oral vaccine platform driving intestinal and systemic immune responses.

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A Study of Secretory IgA Antibody Titers for Chlamydia trachomatis Prostatic Secretion of Chronic Prostatitis

Kansenshogaku zasshi ◽

10.11150/kansenshogakuzasshi1970.65.262 ◽

1991 ◽

Vol 65 (3) ◽

pp. 262-266 ◽

Cited By ~ 1

Author(s):

Takuji TSUNEKAWA ◽

Yoshiaki KUMAMOTO ◽

Kenji HAYASHI ◽

Takashi SATOH

Keyword(s):

Chlamydia Trachomatis ◽

Chronic Prostatitis ◽

Secretory Iga ◽

Antibody Titers ◽

Iga Antibody

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Escherichia coli Nissle 1917 Enhances Efficacy of Oral Attenuated Human Rotavirus Vaccine in a Gnotobiotic Piglet Model

Vaccines ◽

10.3390/vaccines10010083 ◽

2022 ◽

Vol 10 (1) ◽

pp. 83

Author(s):

Husheem Michael ◽

Ayako Miyazaki ◽

Stephanie N. Langel ◽

Joshua O. Amimo ◽

Maryssa K. Kick ◽

...

Keyword(s):

Escherichia Coli ◽

Cell Function ◽

Protective Efficacy ◽

Oral Vaccine ◽

Cell Immune Response ◽

Viral Gastroenteritis ◽

Human Rotavirus ◽

Antibody Titers ◽

Iga Antibody ◽

Escherichia Coli Nissle

Human rotavirus (HRV) infection is a major cause of viral gastroenteritis in young children worldwide. Current oral vaccines perform poorly in developing countries where efficacious vaccines are needed the most. Therefore, an alternative affordable strategy to enhance efficacy of the current RV vaccines is necessary. This study evaluated the effects of colonization of neonatal gnotobiotic (Gn) pigs with Escherichia coli Nissle (EcN) 1917 and Lacticaseibacillus rhamnosus GG (LGG) probiotics on immunogenicity and protective efficacy of oral attenuated (Att) HRV vaccine. EcN-colonized pigs had reduced virulent HRV (VirHRV) shedding and decreased diarrhea severity compared with the LGG-colonized group. They also had enhanced HRV-specific IgA antibody titers in serum and antibody secreting cell numbers in tissues pre/post VirHRV challenge, HRV-specific IgA antibody titers in intestinal contents, and B-cell subpopulations in tissues post VirHRV challenge. EcN colonization also enhanced T-cell immune response, promoted dendritic cells and NK cell function, reduced production of proinflammatory cytokines/Toll like receptor (TLR), and increased production of immunoregulatory cytokines/TLR expression in various tissues pre/post VirHRV challenge. Thus, EcN probiotic adjuvant with AttHRV vaccine enhances the immunogenicity and protective efficacy of AttHRV to a greater extent than LGG and it can be used as a safe and economical oral vaccine adjuvant.

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Antibody in Middle Ear Fluid of Children Originates Predominantly from Sera and Nasopharyngeal Secretions

Clinical and Vaccine Immunology ◽

10.1128/cvi.05443-11 ◽

2012 ◽

Vol 19 (10) ◽

pp. 1593-1596 ◽

Cited By ~ 15

Author(s):

Ravinder Kaur ◽

Thomas Kim ◽

Janet R. Casey ◽

Michael E. Pichichero

Keyword(s):

Middle Ear ◽

Acute Otitis Media ◽

Secretory Iga ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Samples ◽

Two Dimensional Gel Electrophoresis ◽

Middle Ear Fluid ◽

Iga Antibodies ◽

Iga Antibody ◽

Entire Array

ABSTRACTThe human middle ear is devoid of any immunocompetent cells in normal mucosa. We sought to determine the source of antibody present in the middle ear of children. Total IgG, IgA, and secretory IgA antibodies were determined by enzyme-linked immunosorbent assay from the nasopharyngeal, middle ear, and serum samples of children with acute otitis media. The two-dimensional gel electrophoresis pattern of the entire array of IgA antibodies in the nasal wash (NW) and middle ear fluid (MEF) was compared from the MEF and NW samples using isoelectric focusing and Western blotting. The total IgG and IgA antibodies in the MEF and NW samples of 137 children were compared. The ratio of IgG to IgA in the MEF was significantly different (P< 0.008) compared to NW because IgA levels were higher and IgG levels lower in NW. The IgG/IgA ratio of MEF resembled serum consistent with transudation to the MEF. Small amounts of secretory IgA were detected in MEF but the electrophoresis patterns of the entire array of IgA antibodies in the MEF and NW were virtually identical in each child evaluated; thus, IgA in MEF derived predominantly from serum and the nasopharynx by reflux via the Eustachian tube. The IgG/IgA antibody levels in the MEF and the same composition of IgA antibody in the MEF and NW identifies the predominant source of antibody in the MEF as a transudate of serum combined with nasal secretions refluxed from the nasopharynx in children.

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Secretory IgA antibody response against Escherichia coli antigens in infants in relation to exposure

The Journal of Pediatrics ◽

10.1016/s0022-3476(85)80528-x ◽

1985 ◽

Vol 107 (3) ◽

pp. 430-433 ◽

Cited By ~ 71

Author(s):

L. Mellander ◽

B. Carlsson ◽

Fehmida Jalil ◽

T. Söderström ◽

L.Å. Hanson

Keyword(s):

Escherichia Coli ◽

Antibody Response ◽

Secretory Iga ◽

Iga Antibody

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Association between serum anti-glycopeptidolipid-core IgA antibody titers and clinical characteristics of Mycobacterium avium complex pulmonary disease

International Journal of Infectious Diseases ◽

10.1016/j.ijid.2021.06.042 ◽

2021 ◽

Author(s):

Norio Kodaka ◽

Chihiro Nakano ◽

Takeshi Oshio ◽

Kayo Watanabe ◽

Kumiko Niitsuma ◽

...

Keyword(s):

Pulmonary Disease ◽

Mycobacterium Avium ◽

Clinical Characteristics ◽

Mycobacterium Avium Complex ◽

Antibody Titers ◽

Iga Antibody

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Study of Antibody Levels in Children with Purulent Otitis Media

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894800890s331 ◽

1980 ◽

Vol 89 (3_suppl) ◽

pp. 117-120 ◽

Cited By ~ 2

Author(s):

P. Branefors ◽

T. Dahlberg ◽

O. Nylén

Keyword(s):

Otitis Media ◽

Serum Antibody ◽

Acute Otitis Media ◽

High Serum ◽

Haemophilus Influenzae Type ◽

Enzyme Linked Immunosorbent Assay ◽

Polysaccharide Antigens ◽

Antibody Titers ◽

Iga Antibody ◽

Antibody Levels

A series of episodes of acute otitis media were studied with reference to the bacterial findings in the nasopharynx and the specific antibody response in a group of children nine months to ten years of age, with previous frequent episodes of acute otitis media, Serum IgG, IgM and IgA antibody levels against five polysaccharide antigens, namely Haemophilus influenzae type b and Streptococcus pneumoniae types 3, 6, 19 and 23, were studied by means of an enzyme-linked immunosorbent assay. The selection of polysaccharide antigens was based on isolation frequency. The sera to be tested were tenfold serially diluted. An extinction of 0.2 over the base was taken as the end-point titer and expressed as in-log10. The results showed that most children including those under three years of age showed increasing homologous antibody titers at an infection, or had already initially very high antibody titers, especially of the IgG class. The titers reached levels of 104 to 105. In some cases, however, it could be shown that high serum antibody titers did not give protection against a new infection with the same serological type of bacteria. It was also demonstrated that most children, regardless of age, had IgG and IgM titers against the heterologous antigens. In some cases the levels were quite high (103 to 104). However, the IgA antibody levels were lower and in a considerable number of samples antibodies were not even detectable.

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Cytokines, Antibodies, and Histopathological Profiles duringGiardiaInfection and Variant-Specific Surface Protein-Based Vaccination

Infection and Immunity ◽

10.1128/iai.00773-17 ◽

2018 ◽

Vol 86 (6) ◽

pp. e00773-17 ◽

Cited By ~ 11

Author(s):

Marianela C. Serradell ◽

Pablo R. Gargantini ◽

Alicia Saura ◽

Sergio R. Oms ◽

Lucía L. Rupil ◽

...

Keyword(s):

Specific Surface ◽

Oral Vaccine ◽

Surface Protein ◽

Meriones Unguiculatus ◽

Surface Proteins ◽

Secretory Iga ◽

Mesenteric Lymph Nodes ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses

ABSTRACTGiardiasis is one of the most common human intestinal diseases worldwide. Several experimental animal models have been used to evaluateGiardiainfections, with gerbils (Meriones unguiculatus) being the most valuable model due to their high susceptibility toGiardiainfection, abundant shedding of cysts, and pathophysiological alterations and signs of disease similar to those observed in humans. Here, we report cytokine and antibody profiles both during the course ofGiardiainfection in gerbils and after immunization with a novel oral vaccine comprising a mixture of purified variant-specific surface proteins (VSPs). Transcript levels of representative cytokines of different immune profiles as well as macro- and microtissue alterations were assessed in Peyer's patches, mesenteric lymph nodes, and spleens. During infection, cytokine responses showed a biphasic profile: an early induction of Th1 (gamma interferon [IFN-γ], interleukin-1β [IL-1β], IL-6, and tumor necrosis factor [TNF]), Th17 (IL-17), and Th2 (IL-4) cytokines, together with intestinal alterations typical of inflammation, followed by a shift toward a predominant Th2 (IL-5) response, likely associated with a counterregulatory mechanism. Conversely, immunization with an oral vaccine comprising the entire repertoire of VSPs specifically showed high levels of IL-17, IL-6, IL-4, and IL-5, without obvious signs of inflammation. Both immunized and infected animals developed local (intestinal secretory IgA [S-IgA]) and systemic (serum IgG) humoral immune responses against VSPs; however, only infected animals showed evident signs of giardiasis. This is the first comprehensive report of cytokine expression and anti-Giardiaantibody production during infection and VSP vaccination in gerbils, a reliable model of the human disease.

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Effects of Euglena gracilis EOD-1 Ingestion on Salivary IgA Reactivity and Health-Related Quality of Life in Humans

Nutrients ◽

10.3390/nu11051144 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1144 ◽

Cited By ~ 5

Author(s):

Ken-ichi Ishibashi ◽

Machiko Nishioka ◽

Nobuteru Onaka ◽

Madoka Takahashi ◽

Daisuke Yamanaka ◽

...

Keyword(s):

Quality Of Life ◽

Euglena Gracilis ◽

Health Related Quality ◽

Salivary Iga ◽

Health Related Qol ◽

Related Quality ◽

Health Related ◽

Antibody Titers ◽

Iga Antibody

Euglena gracilis EOD-1, a microalgal strain known for high yields of the β-1, 3-glucan paramylon, is suggested to function as a dietary fiber and enhance immunity. Here, we aimed to investigate the effects of E. gracilis EOD-1 biomass (EOD1BM) ingestion on immunoglobulin A (IgA) antibody titers in saliva, its reactivity, and the health-related quality of life (QOL) in humans. Reacting human immunoglobulin preparations and saliva with paramylon granules revealed the presence of anti-paramylon antibodies in the blood and saliva. We conducted a placebo-controlled, double-blind, crossover study involving 13 healthy subjects who ingested the placebo or EOD1BM for 4 weeks. Saliva was collected from each subject before and after ingestion, and IgA titers and E. gracilis EOD-1 paramylon (EOD1PM) reactivity were compared. In the EOD1BM Ingestion group, the anti-EOD1PM IgA content and titer increased after EOD1BM ingestion. No such change was observed in the Placebo group. Furthermore, the health-related QOL, especially mental health, increased in the EOD1BM Ingestion group. Thus, EOD1BM ingestion led to the production of paramylon (PM)-specific IgA antibody and increased salivary IgA antibody titers. We demonstrate that EOD1BM ingestion enhanced the immunity in the mucosal surface, evoked an antigen-specific response, and increased the health-related QOL, thereby contributing to health improvement.

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