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21 results on '"Giles, Brendan M."'

3. Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA

Author

Zhao, Jian, Giles, Brendan M, Taylor, Rhonda L, Yette, Gabriel A, Lough, Kara M, Ng, Han Leng, Abraham, Lawrence J, Wu, Hui, Kelly, Jennifer A, Glenn, Stuart B, Adler, Adam J, Williams, Adrienne H, Comeau, Mary E, Ziegler, Julie T, Marion, Miranda, Alarcón-Riquelme, Marta E, Alarcón, Graciela S, Anaya, Juan-Manuel, Bae, Sang-Cheol, Kim, Dam, Lee, Hye-Soon, Criswell, Lindsey A, Freedman, Barry I, Gilkeson, Gary S, Guthridge, Joel M, Jacob, Chaim O, James, Judith A, Kamen, Diane L, Merrill, Joan T, Sivils, Kathy Moser, Niewold, Timothy B, Petri, Michelle A, Ramsey-Goldman, Rosalind, Reveille, John D, Scofield, R Hal, Stevens, Anne M, Vilá, Luis M, Vyse, Timothy J, Kaufman, Kenneth M, Harley, John B, Langefeld, Carl D, Gaffney, Patrick M, Brown, Elizabeth E, Edberg, Jeffrey C, Kimberly, Robert P, Ulgiati, Daniela, Tsao, Betty P, and Boackle, Susan A

Published
2016
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8. Analytical Characterization of an Enzyme-Linked Immunosorbent Assay for the Measurement of Transforming Growth Factor β1 in Human Plasma

Author

Giles, Brendan M, primary, Underwood, Timothy T, additional, Benhadji, Karim A, additional, Nelson, Diana K S, additional, Grobeck, Lisa M, additional, Lin, Boris, additional, Wang, Shuaicheng, additional, Fill, Jeffrey A, additional, Man, Michael, additional, Pitts, Kelly R, additional, and Bamberg, Alison, additional

Published
2018
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10. Acute Murine H5N1 Influenza A Encephalitis

Author

Bissel, Stephanie J, Giles, Brendan M, Wang, Guoji, Olevian, Dane C., Ross, Ted M., and Wiley, Clayton A.

Subjects
Mice, Inbred BALB C, Influenza A Virus, H5N1 Subtype, animal diseases, Pneumonia, Viral, virus diseases, Article, Disease Models, Animal, Mice, Orthomyxoviridae Infections, Acute Disease, Animals, Humans, Female, Encephalitis, Viral
Abstract

Avian influenza A virus H5N1 has the proven capacity to infect humans through cross-species transmission, but to date, efficient human-to-human transmission is limited. In natural avian hosts, animal models and sporadic human outbreaks, H5N1 infection has been associated with neurological disease. We infected BALB/c mice intranasally with H5N1 influenza A/Viet Nam/1203/2004 to study the immune response during acute encephalitis. Using immunohistochemistry and in situ hybridization, we compared the time course of viral infection with activation of immunity. By 5 days postinfection (DPI), mice had lost substantial body weight and required sacrifice by 7 DPI. H5N1 influenza was detected in the lung as early as 1 DPI, whereas infected neurons were not observed until 4 DPI. H5N1 infection of BALB/c mice developed into severe acute panencephalitis. Infected neurons lacked evidence of a perineuronal net and exhibited signs of apoptosis. Whereas lung influenza infection was associated with an early type I interferon (IFN) response followed by a reduction in viral burden concordant with appearance of IFN-γ, the central nervous system environment exhibited a blunted type I IFN response.

Published
2011

11. Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA.

Author

Jian Zhao, Giles, Brendan M., Taylor, Rhonda L., Yette, Gabriel A., Lough, Kara M., Han Leng Ng, Abraham, Lawrence J., Hui Wu, Kelly, Jennifer A., Glenn, Stuart B., Adler, Adam J., Williams, Adrienne H., Comeau, Mary E., Ziegler, Julie T., Marion, Miranda, Alarcón-Riquelme, Marta E., Alarcón, Graciela S., Anaya, Juan-Manuel, Sang-Cheol Bae, and Dam Kim

Subjects
AUTOANTIBODIES, B cells, CELL receptors, DISEASE susceptibility, DNA, GENETIC polymorphisms, GENETICS, RESEARCH funding, RISK assessment, SYSTEMIC lupus erythematosus, TRANSCRIPTION factors, PHENOTYPES, CASE-control method, HAPLOTYPES, GENOTYPES
Abstract

Objectives: Systemic lupus erythematosus (SLE; OMIM 152700) is characterised by the production of antibodies to nuclear antigens. We previously identified variants in complement receptor 2 (CR2/CD21) that were associated with decreased risk of SLE. This study aimed to identify the causal variant for this association.Methods: Genotyped and imputed genetic variants spanning CR2 were assessed for association with SLE in 15 750 case-control subjects from four ancestral groups. Allele-specific functional effects of associated variants were determined using quantitative real-time PCR, quantitative flow cytometry, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP)-PCR.Results: The strongest association signal was detected at rs1876453 in intron 1 of CR2 (pmeta=4.2×10(-4), OR 0.85), specifically when subjects were stratified based on the presence of dsDNA autoantibodies (case-control pmeta=7.6×10(-7), OR 0.71; case-only pmeta=1.9×10(-4), OR 0.75). Although allele-specific effects on B cell CR2 mRNA or protein levels were not identified, levels of complement receptor 1 (CR1/CD35) mRNA and protein were significantly higher on B cells of subjects harbouring the minor allele (p=0.0248 and p=0.0006, respectively). The minor allele altered the formation of several DNA protein complexes by EMSA, including one containing CCCTC-binding factor (CTCF), an effect that was confirmed by ChIP-PCR.Conclusions: These data suggest that rs1876453 in CR2 has long-range effects on gene regulation that decrease susceptibility to lupus. Since the minor allele at rs1876453 is preferentially associated with reduced risk of the highly specific dsDNA autoantibodies that are present in preclinical, active and severe lupus, understanding its mechanisms will have important therapeutic implications. [ABSTRACT FROM AUTHOR]

Published
2016
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20. Antibody Breadth and Protective Efficacy Are Increased by Vaccination with Computationally Optimized Hemagglutinin but Not with Polyvalent Hemagglutinin-Based H5N1 Virus-Like Particle Vaccines

Author

Giles, Brendan M., Bissel, Stephanie J., DeAlmeida, Dilhari R., Wiley, Clayton A., and Ross, Ted M.

Abstract

ABSTRACTOne of the challenges for developing an H5N1 influenza vaccine is the diversity of antigenically distinct isolates within this subtype. Previously, our group described a novel hemagglutinin (HA) derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA, when used as an immunogen, elicits a broad antibody response against H5N1 isolates from different clades. In this report, the immune responses elicited by the COBRA HA virus-like particle (VLP) vaccine were compared to responses elicited by a mixture of VLPs expressing representative HA molecules from clade 2.1, 2.2, and 2.3 primary H5N1 isolates (polyvalent). The COBRA HA VLP vaccine elicited higher-titer antibodies to a panel of H5N1 HA proteins than did the other VLPs. Both COBRA and polyvalent vaccines protected vaccinated mice and ferrets from experimental infection with highly lethal H5N1 influenza viruses, but COBRA-vaccinated animals had decreased viral replication, less inflammation in the lungs of mice, and reduced virus recovery in ferret nasal washes. Both vaccines had similar cellular responses postchallenge, indicating that higher-titer serum antibodies likely restrict the duration of viral replication. Furthermore, passively transferred immune serum from the COBRA HA VLP-vaccinated mice protected recipient animals more efficiently than immune serum from polyvalent-vaccinated mice. This is the first report comparing these two vaccine strategies. The single COBRA HA antigen elicited a broader antibody response and reduced morbidity and viral titers more effectively than a polyvalent mixture of primary H5N1 HA antigens.

Published
2011
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21. Development of a broadly reactive vaccine for highly pathogenic H5N1 influenza

Author

Giles, Brendan M.

Abstract

Emerging and re-emerging infectious diseases are increasing throughout the world and highly pathogenic influenza is among those that pose a significant threat to mankind. Pandemic outbreaks of influenza are caused by the emergence of a highly pathogenic and transmissible virus to which the human population is immunologically naïve. Ongoing outbreaks of highly pathogenic avian influenza of the H5N1 subtype are of particular concern because of the high mortality rate (>60%) and novel subtype. Vaccines are considered the most effective way to prevent the morbidity and mortality associated with pandemic influenza and therefore developing an H5N1 vaccine is a public health priority. One of the hurdles facing H5N1 vaccine development is the antigenic diversity of the subtype as evidenced by the identification of ten phylogenetic clades. To overcome the challenge of antigenic diversity, a centralized hemagglutinin was developed and termed computationally optimized broadly reactive antigen (COBRA). The COBRA HA sequence was based upon HA amino acid sequences from clade 2 H5N1 human infections and the expressed protein retained the ability to bind the receptor, as well as mediate particle fusion. COBRA virus-like particle (VLP) vaccines elicited broadly reactive receptor blocking antibodies in multiple animal species: mice, ferrets and non-human primates. The reactivity profile was broader than that elicited by primary isolate-based vaccines given in either monovalent or polyvalent formulations. Although all vaccinated animals were protected from severe disease and death from experimental infection with highly pathogenic H5N1 virus, animals receiving the COBRA vaccine had reduced peak virus replication and cleared the infection more rapidly. COBRA vaccines were shown to be superior to primary isolate-based vaccines with both a broader antibody profile and more efficient protective efficacy. The development of COBRA resulted in a novel antigen generation methodology that is applicable to both pandemic and seasonal influenza.

Published
2011

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