Rotavirus immune response

Nearly 45% of under 5 mortality is directly or indirectly linked to malnutrition. Infection adds to the increased mortality and morbidity in these groups. Vaccination is very important in these undernourished children protecting against life-threatening infections. The goal of vaccination is to produce long-term protection by generating memory cells and the generation of antibodies. Since malnutrition is a state of immunodeficiency, the immune response to vaccines in these children is a matter of concern. We did an exhaustive search to gather more recent studies and corroborated previous findings...

BACKGROUND: Rotavirus gastroenteritis remains a leading cause of morbidity and mortality despite the introduction of vaccines. Research shows there are several factors contributing to the reduced efficacy of rotavirus vaccines in low- and middle-income settings. Proposed factors include environmental enteric dysfunction (EED), malnutrition, and immune dysfunction. This study aimed to assess the effect of these factors on vaccine responses using a machine learning lasso approach. METHODS: Serum samples from two rotavirus clinical trials (CVIA 066 n = 99 and CVIA 061 n = 124) were assessed for 11 analytes using the novel Micronutrient and EED Assessment Tool (MEEDAT) multiplex ELISA...

The WHO pre-qualified rotavirus vaccine, ROTAVAC®, is derived naturally from the neonatal 116E rotavirus strain, and stored at -20°C. As refrigerator storage is preferable, immunogenicity and safety of liquid formulations kept at 2-8°C, having excipients to stabilize the rotavirus, with or without buffers, were compared with ROTAVAC® in different clinical studies. Study-1, the pivotal trial for this entire product development work, was a randomized, single-blind trial with two operationally seamless phases: (i) an exploratory phase involving 675 infants in which two formulations, ROTAVAC 5C (LnHRV-1...

Severe combined immunodeficiency (SCID) is one of the most serious inborn errors of immunity leading to a fatal infection in early infancy. Allogeneic hematopoietic cell transplantation (HCT) or elective gene therapy prior to infection or live-attenuated vaccination is the current standard of curative treatment. Even in the era of newborn screening for SCID, pretransplant control of severe infection is challenging for SCID. Multiple pathogens are often isolated from immunocompromised patients, and limited information is available regarding antiviral strategies to facilitate curative HCT...

The binding of viral RNA to RIG-I-like receptors triggers the formation of mitochondrial antiviral signaling (MAVS) protein aggregates critical for interferon (IFN) expression. Several rotavirus strains have been shown to suppress IFN expression by inducing MAVS degradation. Relying on transient expression assays, previous studies reached different conclusions regarding the identity of the rotavirus protein responsible for MAVS degradation, suggesting it was an activity of the rotavirus capping enzyme VP3 or the interferon antagonist NSP1...

Despite the success of rotavirus vaccines, rotaviruses remain one of the leading causes of diarrheal diseases, resulting in significant childhood morbidity and mortality, especially in low- and middle-income countries. The reverse genetics system enables the manipulation of the rotavirus genome and opens the possibility of using rotavirus as an expression vector for heterologous proteins, such as vaccine antigens and therapeutic payloads. Here, we demonstrate that three positions in rotavirus genome-the C terminus of NSP1, NSP3 and NSP5-can tolerate the insertion of reporter genes...

BACKGROUND: Uganda, like many other developing countries, faces the challenges of unreliable estimates for its immunization target population. Strengthening immunization data quality and its use for improving immunization program performance are critical steps toward improving coverage and equity of immunization programs. The goal of this study was to determine the effectiveness of using community health workers (CHWs) to obtain quality and reliable data that can be used for planning and evidence-based response actions...

BACKGROUND: Rotavirus C (RVC) is the major causative agent of acute gastroenteritis in suckling piglets, while most RVAs mostly affect weaned animals. Besides, while most RVA strains can be propagated in MA-104 and other continuous cell lines, attempts to isolate and culture RVC strains remain largely unsuccessful. The host factors associated with these unique RVC characteristics remain unknown. METHODS: In this study, we have comparatively evaluated transcriptome responses of porcine ileal enteroids infected with RVC G1P[1] and two RVA strains (G9P[13] and G5P[7]) with a focus on innate immunity and virus-host receptor interactions...

Reverse genetic systems have been used to introduce heterologous sequences into the rotavirus segmented double-stranded (ds)RNA genome, enabling the generation of recombinant viruses that express foreign proteins and possibly serve as vaccine vectors. Notably, insertion of SARS-CoV-2 sequences into the segment seven (NSP3) RNA of simian SA11 rotavirus was previously shown to result in the production of recombinant viruses that efficiently expressed the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the S1 region of the SARS-CoV-2 spike protein...

Antibodies that can bind to viruses but are unable to block infection in cell culture are known as "nonneutralizing antibodies." Such antibodies are nearly universally elicited following viral infection and have been characterized in viral infections such as influenza, rotavirus, cytomegalovirus, HIV, and SARS-CoV-2. It has been widely assumed that these nonneutralizing antibodies do not function in a protective way in vivo and therefore are not desirable targets of antiviral interventions; however, increasing evidence now shows this not to be true...

Vaccination is one of medicine's greatest achievements; however, its full potential is hampered by considerable variation in efficacy across populations and geographical regions. For example, attenuated malaria vaccines in high-income countries confer almost 100% protection, whereas in low-income regions these same vaccines achieve only 20-50% protection. This trend is also observed for other vaccines, such as bacillus Calmette-Guérin (BCG), rotavirus and yellow fever vaccines, in terms of either immunogenicity or efficacy...

Human rotavirus (HRV) is a leading cause of viral gastroenteritis in children across the globe. The virus has long been established as a pathogen of the gastrointestinal tract, targeting small intestine epithelial cells and leading to diarrhea, nausea, and vomiting. Recently, this classical infection pathway was challenged by the findings that murine strains of rotavirus can infect the salivary glands of pups and dams and transmit via saliva from pups to dams during suckling. Here, we aimed to determine if HRV was also capable of infecting salivary glands and spreading in saliva using a gnotobiotic (Gn) pig model of HRV infection and disease...

A correlate of protection for rotavirus (RV) has not been consistently identified. Shedding of RV following an oral rotavirus vaccine (ORV) challenge has been investigated as a potential model to assess protection of parenteral RV vaccines. We previously showed that shedding of a challenge ORV dose was significantly reduced among recipients of a parenteral monovalent RV subunit vaccine (P2-VP8-P[8]) compared to placebo recipients. This secondary data analysis assessed the association between fecal shedding of RV, as determined by ELISA one week after receipt of a Rotarix challenge dose at 18 weeks of age, and serum RV-specific antibody responses, one and six months after vaccination with the third dose of the P2-VP8-P[8] vaccine or placebo...

Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions is less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were horizontally transferred between coronavirus genera...

Among the ramified cellular responses elicited in response to pathogenic stimuli, upregulation and covalent conjugation of an Ubiquitin-like modifier ISG15 to lysine residues of target proteins (ISGylation) through sequential action of three enzymes E1 (Ube1L), E2 (Ube2L6) and E3 (Herc5) have emerged as an important regulatory facet governing innate immunity against numerous viral infections. In the present study, we investigated the interplay between host ISGylation system and Rotavirus (RV). We observed that RV infection upregulates the expression of free ISG15 but prevents protein ISGylation...

BACKGROUND: Cryptosporidium parvum is the main cause of calf scour worldwide. With limited therapeutic options and research compared to other Apicomplexa, it is important to understand the parasites' biology and interactions with the host and microbiome in order to develop novel strategies against this infection. The age-dependent nature of symptomatic cryptosporidiosis suggests a link to the undeveloped immune response, the immature intestinal epithelium, and its associated microbiota...

The definitive role of viral infections, such as rotavirus, in causing Kawasaki disease (KD) remains uncertain. However, the intriguing observation of concomitant rotavirus infection and KD suggests a potential association. This study aimed to investigate this relationship. We reported a case of concomitant KD and rotavirus infection complicated by hyponatraemia and anasarca. For the systematic review, we used three large databases, namely PubMed, Ovid, and Scopus, to search articles with the terms "Kawasaki" and "rotavirus"...

BACKGROUND: Histo-blood group antigen (HBGA) status may impact vaccine efficacy due to rotavirus strains binding to HBGAs in a P genotype-dependent manner. This study aimed to determine if HBGA status impacted vaccine take of the G3P[6] neonatal vaccine RV3-BB. METHODS: DNA was extracted from stool samples collected in a subset of participants (n=164) of the RV3-BB Phase IIb trial in Indonesian infants. FUT2 and FUT3 genes were amplified and sequenced, with any single nucleotide polymorphisms analysed to infer the Lewis and secretor status...

OBJECTIVES: Intestinal rotavirus (RV) vaccine replication and host immune response are suggested to be affected by several factors, including maternal antibodies, breastfeeding history, and gut microbiome, which are thought to be similar in pairs of twins. The aim of this study was to determine whether viral shedding from the fecal RV vaccine strain Rotarix® (RV1) and IgG and IgA responses to RV show similarity in pairs of twins. METHODS: Quantitative reverse transcription polymerase chain reaction specific to RV vaccine strain RV1 was used to monitor fecal RV1 viral shedding...

Although rotavirus A (RVA) is the primary cause of acute viral gastroenteritis in children and young animals, mechanisms of its replication and pathogenesis remain poorly understood. We previously demonstrated that the neuraminidase-mediated removal of terminal sialic acids (SAs) significantly enhanced RVA-G9P[13] replication, while inhibiting RVA-G5P[7] replication. In this study, we compared the transcriptome responses of porcine ileal enteroids (PIEs) to G5P[7] vs. G9P[13] infections, with emphasis on the genes associated with immune response, cholesterol metabolism, and host cell attachment...