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

2013 ◽  
Vol 81 (12) ◽  
pp. 4626-4634 ◽  
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.

scholarly journals Humoral Immune Responses in a Human Case of Glanders

2012 ◽  
Vol 19 (5) ◽  
pp. 814-816 ◽  
Author(s):  
David M. Waag ◽  
Marilyn J. England ◽  
David DeShazer
Keyword(s):  
Immune Responses ◽  
Burkholderia Pseudomallei ◽  
Human Case ◽  
Burkholderia Mallei ◽  
Baseline Serum ◽  
Content Type ◽  
Whole Cells ◽  
Humoral Immune ◽  
Diagnostic Antigen ◽  
Humoral Immune Responses

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.

scholarly journals Yersinia pestis caf1 Variants and the Limits of Plague Vaccine Protection

2008 ◽  
Vol 76 (5) ◽  
pp. 2025-2036 ◽  
Author(s):  
Lauriane E. Quenee ◽  
Claire A. Cornelius ◽  
Nancy A. Ciletti ◽  
Derek Elli ◽  
Olaf Schneewind
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Protective Immunity ◽  
Wild Type ◽  
Vaccine Protection ◽  
Subunit Vaccines ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Plague Vaccine ◽  
Highly Virulent

ABSTRACT Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

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

2012 ◽  
Vol 19 (6) ◽  
pp. 825-834 ◽  
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.

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

2015 ◽  
Vol 83 (5) ◽  
pp. 2185-2196 ◽  
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.

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

2012 ◽  
Vol 81 (3) ◽  
pp. 723-732 ◽  
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.

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

2015 ◽  
Vol 23 (1) ◽  
pp. 2-5 ◽  
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.

scholarly journals Yersinia pestis IS1541 Transposition Provides for Escape from Plague Immunity

2009 ◽  
Vol 77 (5) ◽  
pp. 1807-1816 ◽  
Author(s):  
Claire A. Cornelius ◽  
Lauriane E. Quenee ◽  
Derek Elli ◽  
Nancy A. Ciletti ◽  
Olaf Schneewind
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Protective Immunity ◽  
Infectious Agent ◽  
Inhibitory Effect ◽  
Effector Proteins ◽  
Host Cells ◽  
Specific Antibodies ◽  
Humoral Immune ◽  
Humoral Immune Responses

ABSTRACTYersinia pestisis perhaps the most feared infectious agent due to its ability to cause epidemic outbreaks of plague disease in animals and humans with high mortality. Plague infections elicit strong humoral immune responses against the capsular antigen (fraction 1 [F1]) ofY. pestis, and F1-specific antibodies provide protective immunity. Here we asked whetherY. pestisgenerates mutations that enable bacterial escape from protective immunity and isolated a variant with an IS1541insertion incaf1Aencoding the F1 outer membrane usher. Thecaf1A::IS1541insertion prevented assembly of F1 pili and provided escape from plague immunity via F1-specific antibodies without a reduction in virulence in mouse models of bubonic or pneumonic plague. F1-specific antibodies interfere withY. pestistype III transport of effector proteins into host cells, an inhibitory effect that was overcome by thecaf1A::IS1541insertion. These findings suggest a model in which IS1541insertion intocaf1Aprovides for reversible changes in envelope structure, enablingY. pestisto escape from adaptive immune responses and plague immunity.

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