Persistent systemic rotavirus vaccine infection in a child with X‐linked severe combined immunodeficiency

Abstract

Objective The main aims of the present study were to elucidate the systemic group A rotavirus (RVA) infection and to clarify the genetic changes of persistent virus in the X‐linked severe combined immunodeficiency (SCID) patient. Methods RotaTeq vaccine (RV5) genotype‐specific real‐time reverse transcription polymerase chain reaction was used to monitor viral RNA load in serially collected serum and stool samples. Next‐generation sequence analysis was used to determine the genotype of the virus by sequencing 11 gene segments. Polyacrylamide gel electrophoresis (PAGE) analysis was used to identify rearrangement of viral genes. The gene rearrangement was examined in NSP5 gene by using Sanger sequence. Results A 7‐month‐old boy demonstrated chronic diarrhea following the third administration of RV5 and failure to thrive. He was diagnosed with X‐linked SCID and successfully underwent cord blood transplantation. High copy numbers of RV5 genotype G1 RNA were detected in serially collected stool and serum samples and the kinetics of viral RNA loads were correlated with the degree of clinical disease. Next‐generation sequence analysis revealed genetic reassortment at least between the strains WI79‐9/G1P7[5] and WI79‐4/G6P1A[8] in the VP7 gene and the VP4 gene among the vaccine‐derived rotavirus strains. In addition, PAGE analysis suggested genetic rearrangements in several genes, and it was confirmed in the NSP5 gene by sequence analysis. Conclusions The kinetics of RVA RNA load in serum and stool samples was consistent with the clinical course of the patient. Among five genotypes of RV5 vaccine, G1 genotype replicated well in this patient. Reassortment and rearrangements were demonstrated in persistently infected G1 genotype of RV5.

Case Report: Rotavirus Vaccination and Severe Combined Immunodeficiency in Japan

“…The third case (P3) was that of a patient with X-SCID who was vaccinated with RV5 at 9 weeks of age ( 4 ). Three vaccine doses were administered; however, the patient was admitted to the hospital because of diarrhea and weight loss (max −15%) at 5 months.…”

“…Several severe cases of rotavirus gastroenteritis caused by vaccine strains in SCID have been reported overseas ( 2 , 3 ) as well as in Japan ( 4 , 5 ). This report summarizes the cases of five patients with SCID who were vaccinated before being diagnosed with SCID in Japan.…”

Segmented Filamentous Bacteria Prevent and Cure Rotavirus Infection

“…In particular, we discovered that flagellin induces TLR5-mediated innate lymphoid cell (ILC) interleukin-22 (IL-22) production and NLRC4-mediated IL-18 release, which prevents and cures RV infection . Such protection is independent of adaptive immunity in that it is maintained in Rag1-knockout (KO) mice, which, like humans with severe immunodeficiencies, develop chronic RV infection (Bogaert et al, 2016;Oishi et al, 1991;Rosenfeld et al, 2017;Yoshikawa et al, 2019).…”

Life-Threatening Infections Due to Live-Attenuated Vaccines: Early Manifestations of Inborn Errors of Immunity

“…Since 2009, 20 SCID patients have been reported to develop severe or chronic infections of the two rotavirus vaccines [19,20,[186][187][188][189][190][191][192][193][194]], yet no other IEIs have been associated with severe infections due to rotavirus vaccines (Table 1). In these SCID patients, severe diarrhea and vomiting led to life-threatening dehydration in some cases, whereas chronic infections were associated with failure to thrive and prolonged shedding of the virus.…”