Generation of a neutralizing antibody against RD114-pseudotyped viral vectors.

The feline endogenous RD114 glycoprotein has proved to be an attractive envelope to pseudotype both retroviral and lentiviral vectors. As a surface protein, its detection on packaging cells as well as viral particles would be useful in different fields of its use. To address this, we generated a monoclonal antibody against RD114 by immunization of rats, termed 22F10. Once seroconversion was confirmed, purified 22F10 was cloned into murine Fc and characterized with a binding affinity of 10nM. The antibody was used to detect RD114 and its variant envelopes on different stable viral packaging cell lines (FLYRD18 and WinPac-RD). 22F10 was also shown to prevent the infections of different strains of RD-pseudotyped vectors but not related envelope glycoproteins by blocking cell surface receptor binding. We are the first to report the neutralization of viral particles by a monoclonal αRD114 antibody.

[Antiphospholipid antibody syndrome as a possible cause of paresis in a child]. / La "sindrome da anticorpi antifosfolipidi" come possible causa di una paresi in un bambino.

The Authors report on the case of a 4-year-old boy, admitted to the pediatric department for left hemiplegia. CT scan of the brain was negative on the day of admission but, on the following day, showed 3 small hypodense focal lesions in the posterior branch of the internal capsule, in the knee of the internal capsule and in the posterior parietal region of the cortex. The acute phase almost completely resolved in 10 days. Twenty days after presentation, cerebral angiography showed a thrombosis of an anterior, right perforating vessel, together with the hypoplasia of the horizontal portion of the cerebral anterior artery. The determination of anti-cardiolipin antibodies, even though performed far from the acute phase of the disease, showed a low IgG positivity. Two months after the onset the neurological symptoms completely resolved. In the presence of hypoplasia, narrowing and other lesions of cerebral vessel, it is possible to hypotesize that the occurrence of thrombotic fenomen, ascribable to anti-phaspholipid antibodies, is responsible for the neurological symptoms. The association of thrombosis and anti-phospholipid antibodies suggest that the assessment of anti-phospholipid antibodies should be routinely performed in the presence of thrombotic phenomena.

T-cell engineering by a chimeric T-cell receptor with antibody-type specificity for the HIV-1 gp120.

Immune-based approaches of cell therapy against viral pathogens such as the human immunodeficiency virus type 1 (HIV-1) could be of primary importance for the control of this viral infection. Here, we designed a chimeric cell surface receptor (105TCR) to provide primary human T-lymphocytes with antibody-type specificity for the HIV-1 envelope glycoprotein. This receptor includes the single chain Fv domain of the neutralizing anti-gp120 human monoclonal antibody F105, CD8alpha hinge and the transmembrane and the cytoplasmic domains of TCRzeta. Our results show that 105TCR is expressed at the cellular surface and is capable of recognizing the HIV-1 envelope glycoprotein inducing highly efficient effector T-cell responses, including extracellular signal-regulated kinase phosphorylation and cytokine secretion. Moreover, human primary CD8+ T-lymphocytes transduced by oncoretroviral and lentiviral vectors containing the 105TCR gene are able to mediate in vitro-specific cytolysis of envelope-expressing cells and HIV-1-infected CD4+ T-lymphocytes. These findings suggest that 105TCR is particularly suited for in vivo efficacy studies.