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Surender Khurana - One of the best experts on this subject based on the ideXlab platform.

  • as03 adjuvanted h5n1 vaccine promotes Antibody Diversity and affinity maturation nai titers cross clade h5n1 neutralization but not h1n1 cross subtype neutralization
    NPJ vaccines, 2018
    Co-Authors: Surender Khurana, Elizabeth M Coyle, Jody Manischewitz, Lisa R King, Jin Gao, Ronald N Germain, Pamela L Schwartzberg, John S Tsang, Hana Golding
    Abstract:

    Immune responses to inactivated vaccines against avian influenza are poor due in part to lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses of polyclonal Antibody responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered in presence or absence of AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced Antibody epitope Diversity to viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine. Furthermore, AS03 promoted significant Antibody affinity maturation to properly folded H5-HA1 (but not to HA2) domain, which correlated with neutralization titers against both vaccine and heterologous H5N1 strains. However, no increase in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition Antibody titers. This study provides insight into the differential impacts of AS03 adjuvant on H5N1 vaccine-induced Antibody responses that may help optimize vaccine platforms for future vaccines with improved protection against seasonal and pandemic influenza strains.

  • AS03-adjuvanted H5N1 vaccine promotes Antibody Diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization
    Nature Publishing Group, 2018
    Co-Authors: Surender Khurana, Elizabeth M Coyle, Jody Manischewitz, Lisa R King, Jin Gao, Ronald N Germain, Pamela L Schwartzberg, John S Tsang, Hana Golding, And The Chi Consortium
    Abstract:

    Influenza: understanding the mechanisms of vaccine-boosting additives Adjuvant AS03 improves a bird flu vaccine’s ability to recognize and bind to virion targets. Avian influenza viruses are considered a pandemic threat, and vaccines made from inactivated virus are limited in their efficacy. However, adjuvants such as AS03 have the ability to augment a host’s immunity, prompting Surender Khurana and colleagues from the United States’ Food and Drug Administration to investigate how. In an H5N1 vaccine trial, researchers found that AS03 improved immune responses by increasing the degree, Diversity, and intensity of Antibody binding to viral surface proteins, which likely caused the observed increase in the neutralization of the virus tested as well as efficacy against other H5N1 strains. The AS03-adjuvanted vaccine did not neutralize seasonal H1N1 influenza strains. This study may inform future vaccine development efforts by partially illuminating the effects of AS03

  • influenza virus h1n1pdm09 infections in the young and old evidence of greater Antibody Diversity and affinity for the hemagglutinin globular head domain ha1 domain in the elderly than in young adults and children
    Journal of Virology, 2012
    Co-Authors: Nitin Verma, Hana Golding, Milena Dimitrova, Donald M Carter, Corey J Crevar, Ted M Ross, Surender Khurana
    Abstract:

    The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. We performed in-depth evaluation of Antibody responses generated following H1N1pdm09 infection of naive ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). In addition to hemagglutination inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display libraries (GFPDL) to evaluate the Antibody repertoires against internal genes, hemagglutinin (HA), and neuraminidase (NA) and also measured Antibody affinity for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets demonstrated gradual development of Antibody repertoires with a focus on M1 and HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70 years old) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) than for the younger age groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1) (but not HA2) than those from younger subjects (50% versus <22% 7 M urea resistance, respectively) and lower Antibody dissociation rates using surface plasmon resonance. This is the first study in humans that provides evidence for a qualitatively superior Antibody response in the elderly following H1N1pdm09 infection, indicative of recall of long-term memory B cells or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.

Mengli Chen - One of the best experts on this subject based on the ideXlab platform.

  • characterization of variable region genes and discovery of key recognition sites in the complementarity determining regions of the anti thiacloprid monoclonal Antibody
    International Journal of Molecular Sciences, 2020
    Co-Authors: Pengyan Liu, Yuanhao Guo, Shasha Jiao, Yunyun Chang, Ying Liu, Rubing Zou, Yihua Liu, Mengli Chen
    Abstract:

    Sequence-defined recombinant antibodies (rAbs) have emerged as alternatives to hybridoma-secreted monoclonal antibodies (mAbs) for performing immunoassays. However, the polyploidy nature of hybridomas often leads to the coexistence of aberrant or non-specific functional variable region (VR) gene transcripts, which complicates the identification of correct VR sequences. Herein, we introduced the use of LC-MS/MS combined with next-generation sequencing to characterize VR sequences in an anti-thiacloprid mAb, which was produced by a hybridoma with genetic Antibody Diversity. The certainty of VR sequences was verified by the functional analysis based on the recombinant Antibody (rAb) expressed by HEK293 mammalian cells. The performance of the rAb was similar to that of the parental mAb, with IC50 values of 0.73 and 0.46 μg/L as measured by ELISAs. Moreover, molecular docking analysis revealed that Ser52 (H-CDR2), Trp98, and Trp93 (L-CDR3) residues in the complementarity determining regions (CDRs) of the identified VR sequences predominantly contributed to thiacloprid-specific recognition through hydrogen bonds and the CH-π interaction. Through single-site-directed alanine mutagenesis, we found that Trp98 and Trp93 (L-CDR3) showed high affinity to thiacloprid, while Ser52 (H-CDR2) had an auxiliary effect on the specific binding. This study presents an efficient and reliable way to determine the key recognition sites of hapten-specific mAbs, facilitating the improvement of Antibody properties.

T Sitnikova - One of the best experts on this subject based on the ideXlab platform.

  • coevolution of immunoglobulin heavy and light chain variable region gene families
    Molecular Biology and Evolution, 1998
    Co-Authors: T Sitnikova
    Abstract:

    The gene families encoding the immunoglobulin variable regions of heavy (VH) and light (VL) chains in vertebrates are composed of many genes. However, the gene number and the extent of Diversity among VH and VL gene copies vary with species. To examine the causes of this variation and the evolutionary forces for these multigene families, we conducted a phylogenetic analysis of VH and VL genes from the species of amniotes. The results of our analysis showed that for each species, VH and VL genes have the same pattern of clustering in the trees, and, according to this clustering pattern, the species can be divided into two groups. In the first group of species (humans and mice), VH and VL genes were extensively intermingled with genes from other organisms; in the second group of species (chickens, rabbits, cattle, sheep, swine, and horses), the genes tended to form clusters within the same group of organisms. These results suggest that the VH and VL multigene families have evolved in the same fashion: they have undergone coordinated contraction and expansion of gene repertoires such that each group of organisms is characterized by a certain level of Diversity of VH and VL genes. The extent of Diversity among copies of VH and VL genes in each species is related to the mechanism of generation of Antibody variety. In humans and mice, DNA rearrangement of immunoglobulin variable, Diversity, and joining-segment genes is a main source of Antibody Diversity, whereas in chickens, rabbits, cattle, sheep, swine, and horses, somatic hypermutation and somatic gene conversion play important roles. The evolutionary pattern of VH and VL multigene families is consistent with the birth-and-death model of evolution, yet different levels of diversifying selection seem to operate in the VH and VL genes of these two groups of species.

Hana Golding - One of the best experts on this subject based on the ideXlab platform.

  • as03 adjuvanted h5n1 vaccine promotes Antibody Diversity and affinity maturation nai titers cross clade h5n1 neutralization but not h1n1 cross subtype neutralization
    NPJ vaccines, 2018
    Co-Authors: Surender Khurana, Elizabeth M Coyle, Jody Manischewitz, Lisa R King, Jin Gao, Ronald N Germain, Pamela L Schwartzberg, John S Tsang, Hana Golding
    Abstract:

    Immune responses to inactivated vaccines against avian influenza are poor due in part to lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses of polyclonal Antibody responses following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered in presence or absence of AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced Antibody epitope Diversity to viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted vaccine. Furthermore, AS03 promoted significant Antibody affinity maturation to properly folded H5-HA1 (but not to HA2) domain, which correlated with neutralization titers against both vaccine and heterologous H5N1 strains. However, no increase in heterosubtypic cross-neutralization of Group1-H1N1 seasonal strains was observed. AS03-H5N1 vaccine also induced higher neuraminidase inhibition Antibody titers. This study provides insight into the differential impacts of AS03 adjuvant on H5N1 vaccine-induced Antibody responses that may help optimize vaccine platforms for future vaccines with improved protection against seasonal and pandemic influenza strains.

  • AS03-adjuvanted H5N1 vaccine promotes Antibody Diversity and affinity maturation, NAI titers, cross-clade H5N1 neutralization, but not H1N1 cross-subtype neutralization
    Nature Publishing Group, 2018
    Co-Authors: Surender Khurana, Elizabeth M Coyle, Jody Manischewitz, Lisa R King, Jin Gao, Ronald N Germain, Pamela L Schwartzberg, John S Tsang, Hana Golding, And The Chi Consortium
    Abstract:

    Influenza: understanding the mechanisms of vaccine-boosting additives Adjuvant AS03 improves a bird flu vaccine’s ability to recognize and bind to virion targets. Avian influenza viruses are considered a pandemic threat, and vaccines made from inactivated virus are limited in their efficacy. However, adjuvants such as AS03 have the ability to augment a host’s immunity, prompting Surender Khurana and colleagues from the United States’ Food and Drug Administration to investigate how. In an H5N1 vaccine trial, researchers found that AS03 improved immune responses by increasing the degree, Diversity, and intensity of Antibody binding to viral surface proteins, which likely caused the observed increase in the neutralization of the virus tested as well as efficacy against other H5N1 strains. The AS03-adjuvanted vaccine did not neutralize seasonal H1N1 influenza strains. This study may inform future vaccine development efforts by partially illuminating the effects of AS03

  • influenza virus h1n1pdm09 infections in the young and old evidence of greater Antibody Diversity and affinity for the hemagglutinin globular head domain ha1 domain in the elderly than in young adults and children
    Journal of Virology, 2012
    Co-Authors: Nitin Verma, Hana Golding, Milena Dimitrova, Donald M Carter, Corey J Crevar, Ted M Ross, Surender Khurana
    Abstract:

    The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. We performed in-depth evaluation of Antibody responses generated following H1N1pdm09 infection of naive ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). In addition to hemagglutination inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display libraries (GFPDL) to evaluate the Antibody repertoires against internal genes, hemagglutinin (HA), and neuraminidase (NA) and also measured Antibody affinity for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets demonstrated gradual development of Antibody repertoires with a focus on M1 and HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70 years old) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) than for the younger age groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1) (but not HA2) than those from younger subjects (50% versus <22% 7 M urea resistance, respectively) and lower Antibody dissociation rates using surface plasmon resonance. This is the first study in humans that provides evidence for a qualitatively superior Antibody response in the elderly following H1N1pdm09 infection, indicative of recall of long-term memory B cells or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.

Gary W Litman - One of the best experts on this subject based on the ideXlab platform.

  • generation of immunoglobulin light chain gene Diversity in raja erinacea is not associated with somatic rearrangement an exception to a central paradigm of b cell immunity
    Journal of Experimental Medicine, 1995
    Co-Authors: Michele K Anderson, Michael J Shamblott, Ronda T Litman, Gary W Litman
    Abstract:

    In all vertebrate species examined to date, rearrangement and somatic modification of gene segmental elements that encode portions of the antigen-combining sites of immunoglobulins are integral components of the generation of Antibody Diversity. In the phylogenetically primitive cartilaginous fishes, gene segments encoding immunoglobulin heavy and light chain loci are arranged in multiple clusters, in which segmental elements are separated by only 300-400 bp. In some cases, segmental elements are joined in the germline of nonlymphoid cells (joined genes). Both genomic library screening and direct amplification of genomic DNA have been used to characterize at least 89 different type I light chain gene clusters in the skate, Raja. Analyses of predicted nucleotide sequences and predicted peptide structures are consistent with the distribution of genes into different sequence groups. Predicted amino acid sequence differences are preferentially distributed in complementarity-determining versus framework regions, and replacement-type substitutions exceed neutral substitutions. When specific germline sequences are related to the sequences of individual cDNAs, it is apparent that the joined genes are expressed and are potentially somatically mutated. No evidence was found for the presence of any type I light chain gene in Raja that is not germline joined. The type I light chain gene clusters in Raja appear to represent a novel gene system in which combinatorial and junctional Diversity are absent.