scholarly journals Association of Tuberculin-Boosted Antibody Responses with Pathology and Cell-Mediated Immunity in Cattle Vaccinated with Mycobacterium bovis BCG and Infected with M. bovis

2004 ◽  
Vol 72 (5) ◽  
pp. 2462-2467 ◽  
Author(s):  
Konstantin Lyashchenko ◽  
Adam O. Whelan ◽  
Rena Greenwald ◽  
John M. Pollock ◽  
Peter Andersen ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Humoral Immune ◽  
Humoral Immune Responses

ABSTRACT Vaccine development and our understanding of the pathology of bovine tuberculosis in cattle would be greatly facilitated by definition of the immunological correlates of protection and/or pathology. In this study we analyzed humoral immune responses in Mycobacterium bovis BCG-vaccinated and control cattle (in particular, the relationship between the intradermal comparative tuberculin skin test and serum immunoglobulin G [IgG] responses) against a range of mycobacterial antigens (MPB59, MPB64, MPB70, MPB83, ESAT-6, CFP-10, Acr1, and PstS-1) by multiantigen print immunoassay and conventional enzyme-linked immunosorbent assay. Following M. bovis infection, the comparative tuberculin skin test strongly boosted IgG, IgG1, and IgG2 antibody responses, particularly against MPB83 and MPB70, in unvaccinated cattle but failed to boost these responses, or did so only weakly, in BCG-vaccinated calves. In addition, the skin test-induced increases in MPB83-specific IgG responses correlated positively with bacterial loads and ESAT-6-induced in vitro gamma interferon responses. In conclusion, both the negative correlation of skin test-enhanced MPB83-specific antibody responses with BCG-induced protection and their positive correlation with bacterial loads can serve as useful markers for vaccine efficacy after challenge.

scholarly journals Humoral Immune Responses of White-Tailed Deer (Odocoileus virginianus) to Mycobacterium bovis BCG Vaccination and Experimental Challenge with M. bovis

2009 ◽  
Vol 16 (3) ◽  
pp. 323-329 ◽  
Author(s):  
P. Nol ◽  
K. P. Lyashchenko ◽  
R. Greenwald ◽  
J. Esfandiari ◽  
W. R. Waters ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Progression ◽  
Mycobacterium Bovis ◽  
Rapid Test ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mycobacterial Antigen ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Experimental Challenge

ABSTRACT Monitoring of the kinetics of production of serum antibodies to multiple mycobacterial antigens can be useful as a diagnostic tool for the detection of Mycobacterium bovis infection as well as for the characterization of disease progression and the efficacy of intervention strategies in several species. The humoral immune responses to multiple M. bovis antigens by white-tailed deer vaccinated with BCG orally via a lipid-formulated bait (n = 5), orally in liquid form (n = 5), and subcutaneously (n = 6) were evaluated over time after vaccination and after experimental challenge with virulent M. bovis and were compared to the responses by unvaccinated deer (n = 6). Antibody responses were evaluated by using a rapid test (RT), a multiantigen print immunoassay (MAPIA), a lipoarabinomannan enzyme-linked immunosorbent assay (LAM-ELISA), and immunoblotting to whole-cell sonicate and recombinant antigen MPB83. MAPIA and RT detected minimal to no antibody responses over those at the baseline to multiple M. bovis antigens in vaccinated white-tailed deer after challenge. This was in contrast to the presence of more readily detectable antibody responses in nonvaccinated deer with more advanced disease. The LAM-ELISA results indicated an overall decrease in the level of production of detectable antibodies against lipoarabinomannan-enriched mycobacterial antigen in vaccinated animals compared to that in nonvaccinated animals after challenge. Immunoblot data were inconsistent but did suggest the occurrence of unique antibody responses by certain vaccinated groups to Ag85 and HSP70. These findings support further research toward the improvement and potential use of antibody-based assays, such as MAPIA, RT, and LAM-ELISA, as tools for the antemortem assessment of disease progression in white-tailed deer in both experimental and field vaccine trials.

A Summary of the Third Global Interferon-γ Release Assay Symposium

2013 ◽  
Vol 34 (6) ◽  
pp. 619-624 ◽  
Author(s):  
Antonino Catanzaro ◽  
Charles Daley
Keyword(s):  
Immune Response ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Tests ◽  
The Third ◽  
Specific Antigens ◽  
Ifn Γ

Studies over the past several decades have dramatically increased our understanding of the immune response to Mycobacterium tuberculosis infection, and advances in proteomics and genomics have led to a new class of immune-diagnostic tests, termed interferon-γ (IFN-γ) release assays (IGRAs), which appear to obviate many of the problems encountered with the tuberculin skin test (TST). Worldwide, 2 IGRAs are currently commercially available. QuantiFERON-TB Gold In-Tube (Cellestis) is a third-generation product that uses an enzyme-linked immunosorbent assay to measure IFN-γ generated in whole blood stimulated with M. tuberculosis–specific antigens. T-Spot-TB (Oxford Immunotec) employs enzyme-linked immunosorbent spot technology to enumerate the number of purified lymphocytes that respond to M. tuberculosis–specific antigens by producing IFN-γ. These in vitro tests measure the host immune response to M. tuberculosis–specific antigens, which virtually eliminates false-positive cross reactions caused by bacillus Calmette-Guérin vaccination and/or exposure to environmental nontuberculous mycobacteria that plague the interpretation and accuracy of the tuberculin skin test (TST). The high specificity of IGRAs, together with sensitivity commensurate with or better than that of the TST, promises an accurate diagnosis and the ability to focus tuberculosis-control activities on those who are actually infected with M. tuberculosis. The Third Global Symposium was held over a 3-day period and was presented by the University of California, San Diego, Continuing Medical Education department; slides and sound recordings of each presentation are available at http://cme.ucsd.edu/igras/syllabus.html. A moderated discussion is also available at http://cme.ucsd.edu/igrasvideo. This document provides a summary of the key findings of the meeting, specifically focusing on the use of IGRAs in screening healthcare worker populations.

scholarly journals Purified Hexameric Epstein-Barr Virus-Encoded BARF1 Protein for Measuring Anti-BARF1 Antibody Responses in Nasopharyngeal Carcinoma Patients

2010 ◽  
Vol 18 (2) ◽  
pp. 298-304 ◽  
Author(s):  
E. K. Hoebe ◽  
S. H. Hutajulu ◽  
J. van Beek ◽  
S. J. Stevens ◽  
D. K. Paramita ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Humoral Immune ◽  
Barr Virus ◽  
Humoral Immune Responses ◽  
Human Sera ◽  
Epstein Barr ◽  
Humoral Responses

ABSTRACTWHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n= 155) compared to healthy EBV-positive (n= 56) and EBV-negative (n= 16) individuals. BARF1 (B95-8) expressed inEscherichia coliand baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P= 0.015) than in regional Indonesian controls or EBV-negative individuals (P< 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients.

scholarly journals Limited Local and Systemic Antibody Responses toNeisseria gonorrhoeae during Uncomplicated Genital Infections

1999 ◽  
Vol 67 (8) ◽  
pp. 3937-3946 ◽  
Author(s):  
Spencer R. Hedges ◽  
Matthew S. Mayo ◽  
Jiri Mestecky ◽  
Edward W. Hook ◽  
Michael W. Russell
Keyword(s):  
Immune Responses ◽  
Transmitted Disease ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Genital Infections ◽  
Sexually Transmitted ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Repeated Infections ◽  
Antibody Levels

ABSTRACT Repeated infections with Neisseria gonorrhoeae are common among patients attending sexually transmitted disease clinics. We examined whether previous infections or site of infection altered the local and systemic antigonococcal antibody levels in males and females. Antibodies against N. gonorrhoeae MS11 and the patients’ homologous infecting isolates were measured by enzyme-linked immunosorbent assay. In general, the local and systemic immune responses to gonococci were extremely modest. There was a slight increase in serum immunoglobulin G (IgG) against the MS11 strain and the homologous isolates in infected males. Levels of serum IgA1 antibodies against MS11 were slightly higher in infected than in uninfected females. A history of previous infections with N. gonorrhoeae did not alter the antibody levels in patients with a current infection, suggesting that immunological memory is not induced by uncomplicated gonococcal infections. Antibody responses to infected subjects’ homologous isolates were observed in cervical mucus; IgA1 levels increased while IgG levels decreased. The decline in mucosal IgG against the homologous isolates was less common in subjects having both rectal and cervical infections; otherwise, no effect of rectal involvement was observed. The absence of substantially higher antibody levels to gonococci where there is infection at a site known to contain organized lymphoid tissue suggests that the low levels of responses to uncomplicated infections may not be due simply to an absence of inductive sites in the genital tract. We propose that in addition to its potential ability to avoid the effects of an immune response,N. gonorrhoeae does not elicit strong humoral immune responses during uncomplicated genital infections.

scholarly journals Antibody Responses in Reindeer (Rangifer tarandus) Infected with Mycobacterium bovis

2005 ◽  
Vol 12 (6) ◽  
pp. 727-735 ◽  
Author(s):  
W. R. Waters ◽  
M. V. Palmer ◽  
J. P. Bannantine ◽  
R. Greenwald ◽  
J. Esfandiari ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Specific Antibody ◽  
Rangifer Tarandus ◽  
Skin Testing ◽  
Serum Antibody ◽  
The United States ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Testing Procedures

ABSTRACT Despite having a very low incidence of disease, reindeer (Rangifer tarandus) are subject to tuberculosis (TB) testing requirements for interstate shipment and herd accreditation in the United States. Improved TB tests are desperately needed, as many reindeer are falsely classified as reactors by current testing procedures. Sera collected sequentially from 11 (experimentally) Mycobacterium bovis-infected reindeer and 4 noninfected reindeer were evaluated by enzyme-linked immunosorbent assay (ELISA), immunoblotting, and multiantigen print immunoassay (MAPIA) for antibody specific to M. bovis antigens. Specific antibody was detected as early as 4 weeks after challenge with M. bovis. By MAPIA, sera were tested with 12 native and recombinant antigens, which were used to coat nitrocellulose. All M. bovis-infected reindeer developed responses to MPB83 and a fusion protein, Acr1/MPB83, and 9/11 had responses to MPB70. Other antigens less commonly recognized included MPB59, ESAT-6, and CFP10. Administration of purified protein derivatives for skin testing boosted serum antibody responses, as detected by each of the assays. Of the noninfected reindeer, 2/4 had responses that were detectable immediately following skin testing, which correlated with pathological findings (i.e., presence of granulomatous lesions yet the absence of acid-fast bacteria). The levels of specific antibody produced by infected reindeer appeared to be associated with disease progression but not with cell-mediated immunity. These findings indicate that M. bovis infection of reindeer elicits an antibody response to multiple antigens that can be boosted by skin testing. Serological tests using carefully selected specific antigens have potential for early detection of infections in reindeer.

scholarly journals Assembly of Human Immunodeficiency Virus (HIV) Antigens on Bacteriophage T4: a Novel In Vitro Approach To Construct Multicomponent HIV Vaccines

2006 ◽  
Vol 80 (15) ◽  
pp. 7688-7698 ◽  
Author(s):  
Taheri Sathaliyawala ◽  
Mangala Rao ◽  
Danielle M. Maclean ◽  
Deborah L. Birx ◽  
Carl R. Alving ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Capsid Protein ◽  
Vaccine Development ◽  
Bacteriophage T4 ◽  
Th2 Response ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Phage T4 ◽  
Immunodeficiency Virus

ABSTRACT Bacteriophage T4 capsid is an elongated icosahedron decorated with 155 copies of Hoc, a nonessential highly antigenic outer capsid protein. One Hoc monomer is present in the center of each major capsid protein (gp23*) hexon. We describe an in vitro assembly system which allows display of HIV antigens, p24-gag, Nef, and an engineered gp41 C-peptide trimer, on phage T4 capsid surface through Hoc-capsid interactions. In-frame fusions were constructed by splicing the human immunodeficiency virus (HIV) genes to the 5′ or 3′ end of the Hoc gene. The Hoc fusion proteins were expressed, purified, and displayed on hoc − phage particles in a defined in vitro system. Single or multiple antigens were efficiently displayed, leading to saturation of all available capsid binding sites. The displayed p24 was highly immunogenic in mice in the absence of any external adjuvant, eliciting strong p24-specific antibodies, as well as Th1 and Th2 cellular responses with a bias toward the Th2 response. The phage T4 system offers new direction and insights for HIV vaccine development with the potential to increase the breadth of both cellular and humoral immune responses.

scholarly journals Distinct Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals

2021 ◽  
Vol 11 ◽  
Author(s):  
Savannah E. Butler ◽  
Andrew R. Crowley ◽  
Harini Natarajan ◽  
Shiwei Xu ◽  
Joshua A. Weiner ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Natural Infection ◽  
Severe Disease ◽  
Critical Role ◽  
Health Assessment ◽  
Antibody Responses ◽  
Effector Functions ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Mucosal Antibody

Understanding humoral immune responses to SARS-CoV-2 infection will play a critical role in the development of vaccines and antibody-based interventions. We report systemic and mucosal antibody responses in convalescent individuals who experienced varying severity of disease. Whereas assessment of neutralization and antibody-mediated effector functions revealed polyfunctional antibody responses in serum, only robust neutralization and phagocytosis were apparent in nasal wash samples. Serum neutralization and effector functions correlated with systemic SARS-CoV-2-specific IgG response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. Antibody depletion experiments support the mechanistic relevance of these correlations. Associations between nasal IgA responses, virus neutralization at the mucosa, and less severe disease suggest the importance of assessing mucosal immunity in larger natural infection cohorts. Further characterization of antibody responses at the portal of entry may define their ability to contribute to protection from infection or reduced risk of hospitalization, informing public health assessment strategies and vaccine development efforts.

scholarly journals Features and Functions of Systemic and Mucosal Humoral Immunity Among SARS-CoV-2 Convalescent Individuals

2020 ◽  
Author(s):  
Savannah E Butler ◽  
Andrew R Crowley ◽  
Harini Natarajan ◽  
Shiwei Xu ◽  
Joshua A Weiner ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Critical Role ◽  
Health Assessment ◽  
Inverse Correlation ◽  
Antibody Responses ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Mucosal Antibody ◽  
Assessment Strategies

Understanding humoral immune responses to SARS-CoV-2 infection will play a critical role in the development of vaccines and antibody-based interventions. We report systemic and mucosal antibody responses in convalescent individuals who experienced varying disease severity. Robust antibody responses to diverse SARS-CoV-2 antigens and evidence of elevated responses to endemic CoV were observed among convalescent donors. SARS-CoV-2-specific IgA and IgG responses were often negatively correlated, particularly in mucosal samples, suggesting subject-intrinsic biases in isotype switching. Assessment of antibody-mediated effector functions revealed an inverse correlation between systemic and mucosal neutralization activity and site-dependent differences in the isotype of neutralizing antibodies. Serum neutralization correlated with systemic anti-SARS-CoV-2 IgG and IgM response magnitude, while mucosal neutralization was associated with nasal SARS-CoV-2-specific IgA. These findings begin to map how diverse Ab characteristics relate to Ab functions and outcomes of infection, informing public health assessment strategies and vaccine development efforts.

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