Dataset Information

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE^-/- Mice: Association with Atheroprotection.

ABSTRACT: Atherosclerosis, the underlying pathology of most cardiovascular diseases, is triggered by the retention of apolipoprotein B (apoB)-containing lipoproteins in the arterial wall through electrostatic interactions with glycosaminoglycan (GAG) side chains of proteoglycans. Previously, we reported the antiatherogenic properties of the chimeric monoclonal antibody (mAb) chP3R99-LALA, which binds sulfated GAGs, inhibits low-density lipoprotein (LDL)-chondroitin sulfate (CS) association, and abrogates LDL oxidation and foam cell formation. In preventive and therapeutic settings, apoE-deficient (apoE^-/-) mice immunized with 50??g of this mAb showed reduced atherosclerotic lesions related with the induction of autologous anti-GAG antibodies. Knowing that age and sex are major non-modifiable risk factors in the development of atherosclerosis, the present study aimed to assess the influence of these variables on the capacity of chP3R99-LALA mAb to generate an anti-CS antibody response. Also, we aimed at defining the impact of the dose of chP3R99-LALA on the anti-CS antibody induction and the atheroprotective effect of this mAb in apoE^-/- mice. Neither age nor sex had an impact in the IgG anti-CS antibody response induced by s.c. immunization with this mAb. Moreover, chP3R99-LALA mAb reduced atherosclerotic lesions to a similar extent in both young male and female apoE^-/- mice fed a hypercholesterolemic diet and, in middle-aged female apoE^-/- mice, with spontaneous lesions. On the other hand, increasing the dose of chP3R99-LALA (200 vs. 50??g) elicited an anti-idiotype antibody cascade characterized by higher levels of anti-idiotype (Ab2), anti-anti-idiotype (Ab3), and anti-CS antibody responses. Moreover, this dose increment resulted in a striking reduction of aortic atherosclerotic lesions in immunized mice.

SUBMITTER: Sarduy R

PROVIDER: S-EPMC5334371 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE<sup>-/-</sup> Mice: Association with Atheroprotection.

Sarduy Roger R Brito Victor V Castillo Adriana A Soto Yosdel Y Griñán Tania T Marleau Sylvie S Vázquez Ana María AM

Frontiers in immunology 20170303

Atherosclerosis, the underlying pathology of most cardiovascular diseases, is triggered by the retention of apolipoprotein B (apoB)-containing lipoproteins in the arterial wall through electrostatic interactions with glycosaminoglycan (GAG) side chains of proteoglycans. Previously, we reported the antiatherogenic properties of the chimeric monoclonal antibody (mAb) chP3R99-LALA, which binds sulfated GAGs, inhibits low-density lipoprotein (LDL)-chondroitin sulfate (CS) association, and abrogates ...[more]

PMID: 28316603

Similar Datasets

Project description:BackgroundNew approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed.MethodsWe conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria. The participants received L9LS either intravenously or subcutaneously at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight. Within 2 to 6 weeks after the administration of L9LS, both the participants who received L9LS and the control participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying Plasmodium falciparum (3D7 strain).ResultsNo safety concerns were identified. L9LS had an estimated half-life of 56 days, and it had dose linearity, with the highest mean (±SD) maximum serum concentration (Cmax) of 914.2±146.5 μg per milliliter observed in participants who had received 20 mg per kilogram intravenously and the lowest mean Cmax of 41.5±4.7 μg per milliliter observed in those who had received 1 mg per kilogram intravenously; the mean Cmax was 164.8±31.1 in the participants who had received 5 mg per kilogram intravenously and 68.9±22.3 in those who had received 5 mg per kilogram subcutaneously. A total of 17 L9LS recipients and 6 control participants underwent controlled human malaria infection. Of the 17 participants who received a single dose of L9LS, 15 (88%) were protected after controlled human malaria infection. Parasitemia did not develop in any of the participants who received 5 or 20 mg per kilogram of intravenous L9LS. Parasitemia developed in 1 of 5 participants who received 1 mg per kilogram intravenously, 1 of 5 participants who received 5 mg per kilogram subcutaneously, and all 6 control participants through 21 days after the controlled human malaria infection. Protection conferred by L9LS was seen at serum concentrations as low as 9.2 μg per milliliter.ConclusionsIn this small trial, L9LS administered intravenously or subcutaneously protected recipients against malaria after controlled infection, without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 614 ClinicalTrials.gov number, NCT05019729.).

Dataset Information

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE^-/- Mice: Association with Atheroprotection.

Publications

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE<sup>-/-</sup> Mice: Association with Atheroprotection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE-/- Mice: Association with Atheroprotection.

Publications

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE<sup>-/-</sup> Mice: Association with Atheroprotection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dose-Dependent Induction of an Idiotypic Cascade by Anti-Glycosaminoglycan Monoclonal Antibody in apoE^-/- Mice: Association with Atheroprotection.