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Persistent Infection with Rotavirus Vaccine Strain in Severe Combined Immunodeficiency (SCID) Child: Is Rotavirus Vaccination in SCID Children a Janus Face?

ABSTRACT: We report the first case, to our knowledge, in Italy, of a severe combined immunodeficiency patient with a persistent rotavirus infection due to a vaccine derived strain. Rotavirus was detected by enzyme immunoassays and RT-PCR in stool specimens for five months. The persistent infection was resolved after complete immune reconstitution achieved by hematopoietic stem cell transplantation. This case underlines the importance of neonatal SCID_screening.

SUBMITTER: De Francesco MA

PROVIDER: S-EPMC6963346 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Persistent Infection with Rotavirus Vaccine Strain in Severe Combined Immunodeficiency (SCID) Child: Is Rotavirus Vaccination in SCID Children a Janus Face?

De Francesco Maria Antonia MA Ianiro Giovanni G Monini Marina M Vezzoli Cesare C Schumacher Richard Fabian RF Giliani Silvia S Lorenzin Giovanni G Gurrieri Francesca F Caruso Arnaldo A

Vaccines 20191116 4

We report the first case, to our knowledge, in Italy, of a severe combined immunodeficiency patient with a persistent rotavirus infection due to a vaccine derived strain. Rotavirus was detected by enzyme immunoassays and RT-PCR in stool specimens for five months. The persistent infection was resolved after complete immune reconstitution achieved by hematopoietic stem cell transplantation. This case underlines the importance of neonatal SCID_screening. ...[more]

PMID: 31744133

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Project description:Immunodeficient animals are valuable models for the engraftment of exogenous tissues; they are widely used in many fields, including the creation of humanized animal models, as well as regenerative medicine and oncology. Compared with mice, laboratory rats have a larger body size and can more easily undergo transplantation of various tissues and organs. Considering the absence of high-quality resources of immunodeficient rats, we used the CRISPR/Cas9 genome editing system to knock out the interleukin-2 receptor gamma chain gene (Il2rg) in F344/Jcl rats-alone or together with recombination activating gene 2 (Rag2)-to create a high-quality bioresource that researchers can freely use: severe combined immunodeficiency (SCID) rats. We selected one founder rat with frame-shift mutations in both Il2rg (5-bp del) and Rag2 ([1-bp del+2-bp ins]/[7-bp del+2-bp ins]), then conducted mating to establish a line of immunodeficient rats. The immunodeficiency phenotype was preliminarily confirmed by the presence of severe thymic hypoplasia in Il2rg-single knockout (sKO) and Il2rg/Rag2-double knockout (dKO) rats. Assessment of blood cell counts in peripheral blood showed that the white blood cell count was significantly decreased in sKO and dKO rats, while the red blood cell count was unaffected. The decrease in white blood cell count was mainly caused by a decrease in lymphocytes. Furthermore, analyses of lymphocyte populations via flow cytometry showed that the numbers of B cells (CD3- CD45+) and natural killer cells (CD3- CD161+) were markedly reduced in both knockout rats. In contrast, T cells were markedly reduced but showed slightly different results between sKO and dKO rats. Notably, our immunodeficient rats do not exhibit growth retardation or gametogenesis defects. This high-quality SCID rat resource is now managed by the National BioResource Project in Japan. Our SCID rat model has been used in various research fields, demonstrating its importance as a bioresource.

Dataset Information

Persistent Infection with Rotavirus Vaccine Strain in Severe Combined Immunodeficiency (SCID) Child: Is Rotavirus Vaccination in SCID Children a Janus Face?

Publications

Persistent Infection with Rotavirus Vaccine Strain in Severe Combined Immunodeficiency (SCID) Child: Is Rotavirus Vaccination in SCID Children a Janus Face?

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