Humoral Immune Responses in a Human Case of Glanders

ABSTRACTWithin 2 months of acquiring glanders, a patient developed 8-, 16-, and 4-fold increases, respectively, in specific IgA, IgG, and IgM serological titers againstBurkholderia mallei. Within 14 months of infection, the titers decreased to the baseline. Serum from this patient was also highly reactive againstBurkholderia pseudomalleiwhole cells.Burkholderia malleiwhole cells did not react with sera from patients with other diseases. Therefore, an assay using aB. malleicellular diagnostic antigen may be useful for the serodiagnosis of glanders.

Download Full-text

Correlates of Immune Protection following Cutaneous Immunization with an Attenuated Burkholderia pseudomallei Vaccine

Infection and Immunity ◽

10.1128/iai.00915-13 ◽

2013 ◽

Vol 81 (12) ◽

pp. 4626-4634 ◽

Cited By ~ 26

Author(s):

Ediane B. Silva ◽

Andrew Goodyear ◽

Marjorie D. Sutherland ◽

Nicole L. Podnecky ◽

Mercedes Gonzalez-Juarrero ◽

...

Keyword(s):

Immune Responses ◽

Vaccine Strain ◽

Protective Immunity ◽

Burkholderia Pseudomallei ◽

Partial Protection ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Immune Correlates ◽

Draining Lymph Nodes

ABSTRACTInfections with the Gram-negative bacteriumBurkholderia pseudomallei(melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. Infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections withB. pseudomallei. At present, our understanding of what constitutes effective protective immunity againstB. pseudomalleiinfection remains incomplete. Therefore, we conducted a study to elucidate immune correlates of vaccine-induced protective immunity against acuteB. pseudomalleiinfection. BALB/c and C57BL/6 mice were immunized subcutaneously with a highly attenuated, Select Agent-excludedpurMdeletion mutant ofB. pseudomallei(strain Bp82) and then subjected to intranasal challenge with virulentB. pseudomalleistrain 1026b. Immunization with Bp82 generated significant protection from challenge withB. pseudomallei, and protection was associated with a significant reduction in bacterial burden in lungs, liver, and spleen of immunized mice. Humoral immunity was critically important for vaccine-induced protection, as mice lacking B cells were not protected by immunization and serum from Bp82-vaccinated mice could transfer partial protection to nonvaccinated animals. In contrast, vaccine-induced protective immunity was found to be independent of both CD4 and CD8 T cells. Tracking studies demonstrated uptake of the Bp82 vaccine strain predominately by neutrophils in vaccine-draining lymph nodes and by smaller numbers of dendritic cells (DC) and monocytes. We concluded that protection following cutaneous immunization with a live attenuatedBurkholderiavaccine strain was dependent primarily on generation of effective humoral immune responses.

Download Full-text

Live Oral Typhoid Vaccine Ty21a Induces Cross-Reactive Humoral Immune Responses against Salmonella enterica Serovar Paratyphi A andS. Paratyphi B in Humans

Clinical and Vaccine Immunology ◽

10.1128/cvi.00058-12 ◽

2012 ◽

Vol 19 (6) ◽

pp. 825-834 ◽

Cited By ~ 50

Author(s):

Rezwanul Wahid ◽

Raphael Simon ◽

Shah J. Zafar ◽

Myron M. Levine ◽

Marcelo B. Sztein

Keyword(s):

Immune Responses ◽

Salmonella Enterica ◽

Outer Membrane Proteins ◽

Serum Antibody ◽

Significant Proportion ◽

Field Trials ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Paratyphi B

ABSTRACTEnteric fever caused bySalmonella entericaserovar Paratyphi A infection has emerged as an important public health problem. Recognizing that in randomized controlled field trials oral immunization with attenuatedS. entericaserovar Typhi live vaccine Ty21a conferred significant cross-protection againstS. Paratyphi B but notS. Paratyphi A disease, we undertook a clinical study to ascertain whether humoral immune responses could explain the field trial results. Ty21a immunization of adult residents of Maryland elicited predominantly IgA antibody-secreting cells (ASC) that recognizeS. Typhi lipopolysaccharide (LPS). Cross-reactivity toS. Paratyphi A LPS was significantly lower than that toS. Paratyphi B LPS. ASC producing IgG and IgA that bind LPS from each of theseSalmonellaserovars expressed CD27 and integrin α4β7 (gut homing), with a significant proportion coexpressing CD62L (secondary lymphoid tissue homing). No significant differences were observed in serum antibody against LPS of the different serovars. Levels of IgA B memory (BM) cells toS. Typhi LPS were significantly higher than those againstS. Paratyphi A or B LPS, with no differences observed betweenS. Paratyphi A and B. The response of IgA BMto outer membrane proteins (OMP) fromS. Typhi was significantly stronger than that to OMP ofS. Paratyphi A but similar to that to OMP ofS. Paratyphi B. The percentages of IgG or IgA BMresponders to LPS or OMP from theseSalmonellastrains were similar. Whereas cross-reactive humoral immune responses toS. Paratyphi A or B antigens are demonstrable following Ty21a immunization, they cannot explain the efficacy data gleaned from controlled field trials.

Download Full-text

Impact of Malaria Preexposure on Antiparasite Cellular and Humoral Immune Responses after Controlled Human Malaria Infection

Infection and Immunity ◽

10.1128/iai.03069-14 ◽

2015 ◽

Vol 83 (5) ◽

pp. 2185-2196 ◽

Cited By ~ 26

Author(s):

Joshua M. Obiero ◽

Seif Shekalaghe ◽

Cornelus C. Hermsen ◽

Maxmillian Mpina ◽

Else M. Bijker ◽

...

Keyword(s):

Immune Responses ◽

Intradermal Injection ◽

Content Type ◽

Human Malaria ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Controlled Human Malaria Infection ◽

Circulating Lymphocytes ◽

Ifn Γ

To understand the effect of previous malaria exposure on antiparasite immune responses is important for developing successful immunization strategies. Controlled human malaria infections (CHMIs) using cryopreservedPlasmodium falciparumsporozoites provide a unique opportunity to study differences in acquisition or recall of antimalaria immune responses in individuals from different transmission settings and genetic backgrounds. In this study, we compared antiparasite humoral and cellular immune responses in two cohorts of malaria-naive Dutch volunteers and Tanzanians from an area of low malarial endemicity, who were subjected to the identical CHMI protocol by intradermal injection ofP. falciparumsporozoites. Samples from both trials were analyzed in parallel in a single center to ensure direct comparability of immunological outcomes. Within the Tanzanian cohort, we distinguished one group with moderate levels of preexisting antibodies to asexualP. falciparumlysate and another that, based onP. falciparumserology, resembled the malaria-naive Dutch cohort. PositiveP. falciparumserology at baseline was associated with a lower parasite density at first detection by quantitative PCR (qPCR) after CHMI than that for Tanzanian volunteers with negative serology. Post-CHMI, both Tanzanian groups showed a stronger increase in anti-P. falciparumantibody titers than Dutch volunteers, indicating similar levels of B-cell memory independent of serology. In contrast to the Dutch, Tanzanians failed to increaseP. falciparum-specificin vitrorecall gamma interferon (IFN-γ) production after CHMI, and innate IFN-γ responses were lower inP. falciparumlysate-seropositive individuals than in seronegative individuals. In conclusion, positiveP. falciparumlysate serology can be used to identify individuals with better parasite control but weaker IFN-γ responses in circulating lymphocytes, which may help to stratify volunteers in future CHMI trials in areas where malaria is endemic.

Download Full-text

Enhanced Susceptibility to Citrobacter rodentium Infection in MicroRNA-155-Deficient Mice

Infection and Immunity ◽

10.1128/iai.00969-12 ◽

2012 ◽

Vol 81 (3) ◽

pp. 723-732 ◽

Cited By ~ 31

Author(s):

Simon Clare ◽

Victoria John ◽

Alan W. Walker ◽

Jennifer L. Hill ◽

Cei Abreu-Goodger ◽

...

Keyword(s):

Immune Responses ◽

Bacterial Pathogen ◽

Citrobacter Rodentium ◽

Wild Type ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Control Gene Expression ◽

Gastrointestinal Tissue ◽

Deficient Mice

ABSTRACTMicroRNAs (miRNAs) are small noncoding molecules that control gene expression posttranscriptionally, with microRNA-155 (miR-155) one of the first to be implicated in immune regulation. Here, we show that miR-155-deficient mice are less able to eradicate a mucosalCitrobacter rodentiuminfection than wild-type C57BL/6 mice. miR-155-deficient mice exhibited prolonged colonization associated with a higherC. rodentiumburden in gastrointestinal tissue and spread into systemic tissues. Germinal center formation and humoral immune responses againstC. rodentiumwere severely impaired in infected miR-155-deficient mice. A similarly susceptible phenotype was observed in μMT mice reconstituted with miR-155-deficient B cells, indicating that miR-155 is required intrinsically for mediating protection against this predominantly luminal bacterial pathogen.

Download Full-text

Control of Giardiasis by Interleukin-17 in Humans and Mice—Are the Questions All Answered?

Clinical and Vaccine Immunology ◽

10.1128/cvi.00648-15 ◽

2015 ◽

Vol 23 (1) ◽

pp. 2-5 ◽

Cited By ~ 14

Author(s):

Steven M. Singer

Keyword(s):

Immune Response ◽

Immune Responses ◽

Giardia Lamblia ◽

Antigenic Variation ◽

Interleukin 17 ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Key Factor

ABSTRACTFor years, studies of the immune response toGiardia lambliainfection focused on the production of IgA by infected hosts and antigenic variation by the parasite to escape destruction by this IgA. A new study by Hanevik and colleagues (C. S. Saghaug, S. Sørnes, D. Peirasmaki, S. Svärd, N. Langeland, and K. Hanevik, Clin Vaccine Immunol 23:11–18, 2016,http://dx.doi.org/10.1128/CVI.00419-15) highlights the emerging role of interleukin-17 (IL-17) in immunity to this parasite. Along with recent studies ofGiardiainfections of animals, this work shows that IL-17 appears to be essential for the control of these infections and to be a key factor linking cellular and humoral immune responses.

Download Full-text

Profiling Humoral Immune Responses to Clostridium difficile-Specific Antigens by Protein Microarray Analysis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00190-15 ◽

2015 ◽

Vol 22 (9) ◽

pp. 1033-1039 ◽

Cited By ~ 8

Author(s):

Ola H. Negm ◽

Mohamed R. Hamed ◽

Elizabeth M. Dilnot ◽

Clifford C. Shone ◽

Izabela Marszalowska ◽

...

Keyword(s):

Clostridium Difficile ◽

Immune Responses ◽

Protein Microarray ◽

Enzyme Linked Immunosorbent Assay ◽

Protein Antigens ◽

Igg Antibody ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Specific Antigens

ABSTRACTClostridium difficileis an anaerobic, Gram-positive, and spore-forming bacterium that is the leading worldwide infective cause of hospital-acquired and antibiotic-associated diarrhea. Several studies have reported associations between humoral immunity and the clinical course ofC. difficileinfection (CDI). Host humoral immune responses are determined using conventional enzyme-linked immunosorbent assay (ELISA) techniques. Herein, we report the first use of a novel protein microarray assay to determine systemic IgG antibody responses against a panel of highly purifiedC. difficile-specific antigens, including native toxins A and B (TcdA and TcdB, respectively), recombinant fragments of toxins A and B (TxA4 and TxB4, respectively), ribotype-specific surface layer proteins (SLPs; 001, 002, 027), and control proteins (tetanus toxoid andCandida albicans). Microarrays were probed with sera from a total of 327 individuals with CDI, cystic fibrosis without diarrhea, and healthy controls. For all antigens, precision profiles demonstrated <10% coefficient of variation (CV). Significant correlation was observed between microarray and ELISA in the quantification of antitoxin A and antitoxin B IgG. These results indicate that microarray is a suitable assay for defining humoral immune responses toC. difficileprotein antigens and may have potential advantages in throughput, convenience, and cost.

Download Full-text

The Adjuvant Bordetella Colonization Factor A Attenuates Alum-Induced Th2 Responses and EnhancesBordetella pertussisClearance from Mouse Lungs

Infection and Immunity ◽

10.1128/iai.00935-17 ◽

2018 ◽

Vol 86 (6) ◽

Cited By ~ 7

Author(s):

Jamie Jennings-Gee ◽

Sally Quataert ◽

Tridib Ganguly ◽

Ralph D'Agostino ◽

Rajendar Deora ◽

...

Keyword(s):

Immune Responses ◽

Whooping Cough ◽

Interleukin 17 ◽

Th17 Response ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Colonization Factor ◽

Pathogen Clearance ◽

Mouse Lungs

ABSTRACTThe reemergence of pertussis or whooping cough in several countries highlights the need for better vaccines. Acellular pertussis vaccines (aPV) contain alum as the adjuvant and elicit Th2-biased immune responses that are less effective in protecting against infection than the reactogenic whole-cell pertussis vaccines (wPV), which elicit primarily a Th1/Th17 response. An important goal for the field is to devise aPV that will induce immune responses similar to those of wPV. We show that Bordetella colonization factor A (BcfA), an outer membrane protein fromBordetella bronchiseptica, has strong adjuvant function and elicits cellular and humoral immune responses to heterologous andBordetella pertussisantigens. Addition of BcfA to a commercial aPV resulted in greater reduction ofB. pertussisnumbers from the lungs than that elicited by aPV alone. The more-efficient pathogen clearance was accompanied by increased interleukin-17 (IL-17) and reduced IL-5 and an increased ratio of IgG2/IgG1 antibodies. Thus, our results suggest that BcfA improves aPV-induced responses by modifying the alum-induced Th2-biased aPV response toward Th1/Th17. A redesigned aPV containing BcfA may allow better control of pertussis reemergence by reshaping immune responses to resemble those elicited by wPV immunization.

Download Full-text

Cell-Mediated and Humoral Immune Responses to Bordetella pertussis Inactivated Whole-Cells Encapsulated Alginate Microspheres as a New Vaccine Candidate

Current Pharmaceutical Biotechnology ◽

10.2174/1389201018666170815170515 ◽

2017 ◽

Vol 18 (7) ◽

Cited By ~ 1

Author(s):

Naser M. Dounighi ◽

Fereshteh Shahcheraghi ◽

Mehdi Razzaghi-Abyaneh ◽

Mojtaba Nofeli ◽

Hossein Zolfagharian

Keyword(s):

Immune Responses ◽

Bordetella Pertussis ◽

Vaccine Candidate ◽

Whole Cells ◽

Humoral Immune ◽

Humoral Immune Responses

Download Full-text

Identification of Novel Antigens Recognized by Serum Antibodies in Bovine Tuberculosis

Clinical and Vaccine Immunology ◽

10.1128/cvi.00259-17 ◽

2017 ◽

Vol 24 (12) ◽

Cited By ~ 8

Author(s):

Konstantin P. Lyashchenko ◽

Adrian Grandison ◽

Karen Keskinen ◽

Alina Sikar-Gang ◽

Paul Lambotte ◽

...

Keyword(s):

Immune Responses ◽

Diagnostic Accuracy ◽

Mycobacterium Bovis ◽

Recombinant Proteins ◽

Bovine Tuberculosis ◽

Serum Antibodies ◽

Serum Samples ◽

Content Type ◽

Humoral Immune ◽

Humoral Immune Responses

ABSTRACT Bovine tuberculosis (TB), caused by Mycobacterium bovis, remains an important zoonotic disease posing a serious threat to livestock and wildlife. The current TB tests relying on cell-mediated and humoral immune responses in cattle have performance limitations. To identify new serodiagnostic markers of bovine TB, we screened a panel of 101 recombinant proteins, including 10 polyepitope fusions, by a multiantigen print immunoassay (MAPIA) with well-characterized serum samples serially collected from cattle with experimental or naturally acquired M. bovis infection. A novel set of 12 seroreactive antigens was established. Evaluation of selected proteins in the dual-path platform (DPP) assay showed that the highest diagnostic accuracy (∼95%) was achieved with a cocktail of five best-performing antigens, thus demonstrating the potential for development of an improved and more practical serodiagnostic test for bovine TB.

Download Full-text