Dataset Information

Cross-reactivity between immunoglobulin G antibodies of whales and dolphins correlates with evolutionary distance.

ABSTRACT: Growing morphological and molecular evidence indicates that the porpoises, dolphins, and whales evolved within the even-toed ungulates, formerly known as Artiodactyla. These animals are now grouped in the Cetartiodactyla. We evaluated the antigenic similarity of the immunoglobulin G (IgG) molecules of 15 cetacean species and the domestic cow. The similarity was scored using three distinct antibodies raised against bottlenose dolphin (Tursiops truncatus) IgG in a Western blot, an indirect enzyme-linked immunosorbent assay (ELISA), and a competitive ELISA format. A score was generated for the genetic distance between each species and T. truncatus using the cytochrome b sequence. Each antibody displayed a distinct pattern of reactivity with the IgG antibodies of the various species. The monoclonal antibody (MAb) specific for the gamma heavy chain of T. truncatus was reactive with all monodontids, delphinids, and phocoenids. The light-chain-specific MAb reacted with IgG of delphinoid and phocoenid species and one of the two mysticete species tested. The polyclonal antibody was broadly cross-reactive across all cetaceans and the domestic cow. Using the MAb specific for the gamma heavy chain, the degree of IgG cross-reactivity ranged from less than 17% for the mysticetes to 106% for killer whale Orcinus orca. The IgG in beaked whale and baleen whale sera was significantly less cross-reactive with bottlenose dolphin IgG than sera from other toothed whales. A strong negative correlation was demonstrated between antigenic cross-reactivity of IgG molecules and the genetic distance of their hosts. The data generated will be useful for the development of clinical serodiagnostics in diverse cetacean species.

SUBMITTER: Nollens HH

PROVIDER: S-EPMC2565941 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Cross-reactivity between immunoglobulin G antibodies of whales and dolphins correlates with evolutionary distance.

Nollens Hendrik H HH Ruiz Carolina C Walsh Michael T MT Gulland Frances M D FM Bossart Gregory G Jensen Eric D ED McBain James F JF Wellehan James F X JF

Clinical and vaccine immunology : CVI 20080903 10

Growing morphological and molecular evidence indicates that the porpoises, dolphins, and whales evolved within the even-toed ungulates, formerly known as Artiodactyla. These animals are now grouped in the Cetartiodactyla. We evaluated the antigenic similarity of the immunoglobulin G (IgG) molecules of 15 cetacean species and the domestic cow. The similarity was scored using three distinct antibodies raised against bottlenose dolphin (Tursiops truncatus) IgG in a Western blot, an indirect enzyme- ...[more]

PMID: 18768672

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Project description:BackgroundAnti-drug antibodies (ADAs) to bococizumab were detected in > 40% of subjects in the SPIRE lipid-lowering trials. The risk of cross-reactivity between anti-bococizumab antibodies and other approved anti-proprotein convertase subtilisin/kexin type-9 (PCSK9) monoclonal antibodies (mAbs) was investigated using a single-assay approach.MethodsBococizumab immunogenicity was assessed in SPIRE-HR, a 52-week study. The highest ADA titer sample from each ADA-positive subject (n = 155) was tested in vitro for cross-reactivity to alirocumab and evolocumab using a novel ADA assay approach. Additional specificity tiers within the bococizumab ADA assay against each drug were validated using recombinant PCSK9 as a surrogate cross-reactive positive control. If the highest ADA titer sample showed cross-reactivity, additional samples from that subject were analyzed. Cross-reactivity was determined by the ability of alirocumab or evolocumab to inhibit the sample signal greater than or equal to the cross-reactivity cut-points.ResultsADAs were detected in 44.0% (155/352) of bococizumab-treated subjects, and 27.0% also developed neutralizing antibodies (NAbs). Median ADA and NAb titers ranged from 276 to 526 and 8 to 12 over the course of the study, respectively. From 155 ADA-positive subjects tested for cross-reactivity, one (0.6%) subject showed weak cross-reactivity to both alirocumab and evolocumab. This cross-reactivity signal was transient (from Days 337 to 373) and undetectable at the last ADA-positive timepoint (Day 407).ConclusionA novel, single-assay approach was validated to assess the potential cross-reactivity of anti-bococizumab antibodies to alirocumab and evolocumab. In subjects who developed ADAs to bococizumab, the likelihood of clinically relevant cross-reactivity to marketed anti-PCSK9 mAbs is remote, based on the low frequency of cross-reactivity observed, which was weak in signal inhibition and transient in nature.Clinical trial registrationThe SPIRE-HR study is registered on ClinicalTrials.gov under the identifier NCT01968954.

Project description:Species distribution models (SDMs) are valuable tools for describing the occurrence of species and predicting suitable habitats. This study used generalized additive models (GAMs) and MaxEnt models to predict the relative densities of four cetacean species (sei whale Balaeanoptera borealis, southern right whale Eubalaena australis, Peale's dolphin Lagenorhynchus australis, and Commerson's dolphin Cephalorhynchus commersonii) in neritic waters (?100 m depth) around the Falkland Islands, using boat survey data collected over three seasons (2017-2019). The model predictor variables (PVs) included remotely sensed environmental variables (sea surface temperature, SST, and chlorophyll-a concentration) and static geographical variables (e.g. water depth, distance to shore, slope). The GAM results explained 35 to 41% of the total deviance for sei whale, combined sei whales and unidentified large baleen whales, and Commerson's dolphins, but only 17% of the deviance for Peale's dolphins. The MaxEnt models for all species had low to moderate discriminatory power. The relative density of sei whales increased with SST in both models, and their predicted distribution was widespread across the inner shelf which is consistent with the use of Falklands' waters as a coastal summer feeding ground. Peale's dolphins and Commerson's dolphins were largely sympatric across the study area. However, the relative densities of Commerson's dolphins were generally predicted to be higher in nearshore, semi-enclosed, waters compared with Peale's dolphins, suggesting some habitat partitioning. The models for southern right whales performed poorly and the results were not considered meaningful, perhaps due to this species exhibiting fewer strong habitat preferences around the Falklands. The modelling results are applicable to marine spatial planning to identify where the occurrence of cetacean species and anthropogenic activities may most overlap. Additionally, the results can inform the process of delineating a potential Key Biodiversity Area for sei whales in the Falkland Islands.

Dataset Information

Cross-reactivity between immunoglobulin G antibodies of whales and dolphins correlates with evolutionary distance.

Publications

Cross-reactivity between immunoglobulin G antibodies of whales and dolphins correlates with evolutionary distance.

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