Select Gut Microbiota Impede Rotavirus Vaccine Efficacy.

Background & Aims: The protection provided by rotavirus (RV) vaccines is highly heterogeneous among individuals. We hypothesized that microbiota composition might influence RV vaccine efficacy.

Methods: First, we examined the potential of segmented filamentous bacteria (SFB) colonization to influence RV vaccine efficacy in mice.

Gut-resident C. perfringens impedes rotavirus vaccine efficacy.

Background & Aims: The extent to which live orally-administered rotavirus (RV) vaccines elicit protective immunity is highly heterogeneous. We hypothesized microbiota composition might influence vaccine efficacy.

Methods: We tested this concept by examining extent to which colonizing mice with segmented filamentous bacteria (SFB) influenced RV vaccine efficacy.

Impact and effectiveness of Rotavin-M1 under conditions of routine use in two provinces in Vietnam, 2016-2021, an observational and case-control study.

Background: Half of diarrhea hospitalizations in children aged <5 years in Vietnam are due to rotavirus. Following introduction of a locally developed and licensed oral rotavirus vaccine, Rotavin-M1, into the routine immunization program in two Vietnamese provinces, Nam Dinh and TT Hue, we describe changes in rotavirus positivity among children hospitalized for diarrhea and calculate vaccine effectiveness against moderate-to-severe rotavirus hospitalizations.

Methods: Active rotavirus surveillance among children <5 years began in December 2016 at sentinel hospitals in districts where rotavirus vaccine was introduced in December 2017.

Segmented filamentous bacteria impede rotavirus infection via retinoic acid receptor-mediated signaling.

Prevention of rotavirus (RV) infection by gut-resident segmented filamentous bacteria (SFB) is an example of the influence of gut microbiota composition on enteric viral infection. Yet, the mechanism by which SFB prevents RV infection is poorly understood. A recent report that SFB colonization of germfree mice generates retinoic acid (RA) thus activating RA receptor (RAR) signaling, which protected against Citrobacter rodentium infection, prompted us to investigate whether this pathway might contribute to SFB's protection against RV infection.

Anti-rotavirus antibody measurement in a rotavirus vaccine trial: Choice of vaccine antigen in immunoassays does matter.

In a clinical trial of Bangladeshi infants who received three doses of RotaTeq (ages 6, 10, and 14 weeks), we did a head-to-head assessment of two vaccine virus strains to measure rotavirus IgA in sera. Serum samples collected at pre-dose 1 (age 6 weeks) and post-dose 3 (age 22 weeks) were tested for rotavirus IgA by EIA by using the matching vaccine strain (RotaTeq) and a different vaccine strain (Rotarix) as antigens. Overall, rotavirus IgA seropositivity and titers with each antigen were compared.

Head-to-head comparison of the immunogenicity of RotaTeq and Rotarix rotavirus vaccines and factors associated with seroresponse in infants in Bangladesh: a randomised, controlled, open-label, parallel, phase 4 trial.

Background: A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse.

Methods: We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh).

Rotavirus VP4 Epitope of a Broadly Neutralizing Human Antibody Defined by Its Structure Bound with an Attenuated-Strain Virion.

Rotavirus live-attenuated vaccines, both mono- and pentavalent, generate broadly heterotypic protection. B-cells isolated from adults encode neutralizing antibodies, some with affinity for VP5*, that afford broad protection in mice. We have mapped the epitope of one such antibody by determining the high-resolution cryo-EM structure of its antigen-binding fragment (Fab) bound to the virion of a candidate vaccine strain, CDC-9.

The Role of the VP4 Attachment Protein in Rotavirus Host Range Restriction in an Suckling Mouse Model.

The basis for rotavirus (RV) host range restriction (HRR) is not fully understood but is likely multigenic. RV genes encoding VP3, VP4, NSP1, NSP2, NSP3, and NSP4 have been associated with HRR in various studies. With the exception of NSP1, little is known about the relative contribution of the other RV genes to HRR.

Microneedle patch as a new platform to effectively deliver inactivated polio vaccine and inactivated rotavirus vaccine.

We recently reported a lack of interference between inactivated rotavirus vaccine (IRV) and inactivated poliovirus vaccine (IPV) and their potential dose sparing when the two vaccines were administered intramuscularly either in combination or standalone in rats and guinea pigs. In the present study, we optimized the formulations of both vaccines and investigated the feasibility of manufacturing a combined IRV-IPV dissolving microneedle patch (dMNP), assessing its compatibility and immunogenicity in rats. Our results showed that IRV delivered by dMNP alone or in combination with IPV induced similar levels of RV-specific IgG and neutralizing antibody.

Prevalence and diversity of rotavirus A in pigs: Evidence for a possible reservoir in human infection.

Background: Rotavirus A (RVA) are a group of diverse viruses causing acute gastroenteritis (AGE) in humans and animals. Zoonotic transmission is an important mechanism for rotavirus evolution and strain diversity in humans, but the extent of pigs as a major reservoir for human infection is not clear.

Methods And Findings: We have surveyed 153 pig farms across Taiwan with a total of 4588 porcine stool samples from three age groups from 2014 to 2017.

Impact of rotavirus vaccination on rotavirus hospitalizations in Taiwanese children.

In 2006, two rotavirus vaccines were licensed in Taiwan but were not added to the national immunization schedule. National Health Insurance data from 2003 through 2017 were used to compare rotavirus-associated pediatric hospitalizations before and after vaccine introduction. Rotavirus hospitalization rates among children < 5 years of age significantly declined by 24% (95% confidence interval [CI] 23 - 25%) in post-vaccine compared to pre-vaccine rotavirus seasons.

The Rotavirus Vaccine Story: From Discovery to the Eventual Control of Rotavirus Disease.

Worldwide, rotavirus is the leading pathogen causing severe diarrhea in children and a major cause of under 5 years mortality. In 1998, the first rotavirus vaccine, RotaShield, was licensed in the United States but a rare adverse event, intussusception, led to its withdrawal. Seven years passed before the next generation of vaccines became available, Rotarix (GSK) and Rotateq (Merck), and 11 years later, 2 additional vaccines from India, Rotavac (Bharat) and Rotasiil (Serum Institute), were recommended by World Health Organization for all children.

Cytokine profiles in children with acute intussusception in South Africa.

Serum specimens of children hospitalized with acute intussusception (IS; n = 407) were analyzed for various pro- and anti-inflammatory cytokines to identify host markers specifically for IS compared to other surgical conditions (n = 235) or acute gastroenteritis (AGE; n = 68) in a cross-sectional study design. We showed that children with IS had elevated levels of pro-inflammatory cytokines IFN-γ, TNF-α, MIP-1β, IL-1β, IL-2, IL-6, IL-7, IL-8, and IL-17 as well as anti-inflammatory cytokines IL-1RA, IL-4, IL-5, and IL-13 compared to those admitted with surgical conditions or AGE symptoms, indicating these cytokines as markers for IS. In addition, we showed an increase in C-reactive protein (CRP) levels in children with IS.

Burden and etiology of moderate and severe diarrhea in children less than 5 years of age living in north and south of China: Prospective, population-based surveillance.

Background: Diarrhea remains the leading cause of childhood illness in China. Better understanding of burden and etiology of diarrheal diseases is important for development of effective prevention measures.

Methods: Population-based diarrhea surveillance was conducted in Sanjiang (southern China) year-round and Zhengding (northern China) in autumn/winter.

Metagenomic sequencing generates the whole genomes of porcine rotavirus A, C, and H from the United States.

The genus Rotavirus comprises eight species, designated A to H, and two recently identified tentative species I in dogs and J in bats. Species Rotavirus A, B, C and H (RVA, RVB, RVC and RVH) have been detected in humans and animals. While human and animal RVA are well characterized and defined, complete porcine genome sequences in the GenBank are limited compared to human strains.

An Optimized Reverse Genetics System Suitable for Efficient Recovery of Simian, Human, and Murine-Like Rotaviruses.

An entirely plasmid-based reverse genetics (RG) system was recently developed for rotavirus (RV), opening new avenues for in-depth molecular dissection of RV biology, immunology, and pathogenesis. Several improvements to further optimize the RG efficiency have now been described. However, only a small number of individual RV strains have been recovered to date.

First isolation and whole-genome characterization of a G9P[14] rotavirus strain from a diarrheic child in Egypt.

An unusual group A rotavirus (RVA) strain (RVA/Human-tc/EGY/AS997/2012/G9[14]) was isolated for the first time in a faecal sample from a 6-month-old child who was hospitalized for treatment of acute gastroenteritis in Egypt in 2012. Whole-genome analysis showed that the strain AS997 had a unique genotype constellation: G9-P[14]-I2-R2-C2-M2-A11-N2-T1-E2-H1. Phylogenetic analysis indicated that the strain AS997 had the consensus P[14] genotype constellation with the G9, T1 and H1 reassortment.

Serial Passaging of the Human Rotavirus CDC-9 Strain in Cell Culture Leads to Attenuation: Characterization from and Studies.

Live oral rotavirus vaccines have been developed by serial passaging in cell culture and found to be safe in infants. However, mechanisms for the adaptation and attenuation of rotavirus vaccines are not fully understood. We prepared a human rotavirus vaccine strain, CDC-9 (G1P[8]), which when grown in MA104 cells to passage 11 or 12 (P11/P12) had no nucleotide or amino acid sequence changes from the original virus in stool.

Rotavirus and Type 1 Diabetes-Is There a Connection? A Synthesis of the Evidence.

Although the etiology of type 1 diabetes (T1D) is not well understood, it is believed to comprise both genetic and environmental factors. Viruses are the most well studied environmental trigger, and there is a small but growing body of research on the potential influence of rotavirus on T1D. Rotavirus infections were initially identified as possible triggers of T1D given similarities between viral peptide sequences and T1D autoantigen peptide sequences.

Genome Sequence of a Segmented Filamentous Bacterium Strain That Confers a Rotavirus Resistance Phenotype in Mice.

Segmented filamentous bacteria (SFB) are well appreciated for eliciting Th17 cell immune responses. Here, we report the genome sequence of a murine isolate of SFB, which confers strong protection against rotavirus infection independent of acquired immunity.