Major changes in prevalence and genotypes of rotavirus diarrhea in Beijing, China after RV5 rotavirus vaccine introduction.

To analyze the epidemiological characteristics of group A rotavirus (RVA) diarrhea in Beijing between 2019 and 2022 and evaluate the effectiveness of the RV5 vaccine. Stool specimens were collected from patients with acute diarrhea, and RVA was detected and genotyped. The whole genome of RVA was sequenced by fragment amplification and Sanger sequencing. Phylogenetic trees were constructed using Bayesian and maximum likelihood methods. Descriptive epidemiological methods were used to analyze the characteristics of RVA diarrhea. Test-negative design was used to evaluate the vaccine effectiveness (VE) of the RV5. Compared with 2011-2018, RVA-positive rates in patients with acute diarrhea under 5 years of age and adults decreased significantly between 2019 and 2022, to 9.45% (249/634) and 3.66% (220/6016), respectively. The predominant genotype of RVA had changed from G9-VIP[8]-III between 2019 and 2021 to G8-VP[8]-III in 2022, and P[8] sequences from G8-VP[8]-III strains formed a new branch called P[8]-IIIb. The complete genotype of G8-VP[8]-III was G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2. The VE of 3 doses of RV5 was 90.4% (95% CI: 28.8%-98.7%) against RVA diarrhea. The prevalence of RVA decreased in Beijing between 2019 and 2022, and the predominant genotype changed to G8P[8], which may be related to RV5 vaccination. Continuous surveillance is necessary to evaluate vaccine effectiveness and improve vaccine design.

Prevalence and genetic diversity of rotavirus among children under 5 years of age in China: a meta-analysis.

Background: This meta-analysis was performed to assess the prevalence and circulating strains of rotavirus (RV) among Chinese children under 5 years of age after the implantation of the RV vaccine. Material and methods: Studies published between 2019 and 2023, focused on RV-based diarrhea among children less than 5 years were systematically reviewed using PubMed, Embase, Web of Science, CNKI, Wanfang and SinoMed Data. We synthesized their findings to examine prevalence and genetic diversity of RV after the RV vaccine implementation using a fixed-effects or random-effects model. Results: Seventeen studies met the inclusion criteria for this meta-analysis. The overall prevalence of RV was found to be 19.00%. The highest infection rate was noted in children aged 12-23months (25.79%), followed by those aged 24-35 months (23.91%), and 6-11 months (22.08%). The serotype G9 emerged as the most predominant RV genotype, accounting for 85.48% of infections, followed by G2 (7.70%), G8 (5.74%), G1 (4.86%), and G3 (3.21%). The most common P type was P[8], representing 64.02% of RV cases. Among G-P combinations, G9P[8] was the most frequent, responsible for 78.46% of RV infections, succeeded by G8P[8] (31.22%) and G3P[8] (8.11%). Conclusion: Despite the variation of serotypes observed in China, the G1, G2, G3, G8 and G9 serotypes accounted for most RV strains. The genetic diversity analysis highlights the dynamic nature of RV genotypes, necessitating ongoing surveillance to monitor changes in strain distribution and inform future vaccine strategies.

Recombinant bivalent subunit vaccine combining truncated VP4 from P[7] and P[23] induces protective immunity against prevalent porcine rotaviruses.

Porcine rotaviruses (PoRVs) cause severe economic losses in the swine industry. P[7] and P[23] are the predominant genotypes circulating on farms, but no vaccine is yet available. Here, we developed a bivalent subunit PoRV vaccine using truncated versions (VP4*) of the VP4 proteins from P[7] and P[23]. The vaccination of mice with the bivalent subunit vaccine elicited more robust neutralizing antibodies (NAbs) and cellular immune responses than its components, even at high doses. The bivalent subunit vaccine and inactivated bivalent vaccine prepared from strains PoRVs G9P[7] and G9P[23] were used to examine their protective efficacy in sows and suckling piglets after passive immunization. The immunized sows showed significantly elevated NAbs in the serum and colostrum, and the suckling piglets acquired high levels of sIgA antibodies from the colostrum. Challenging subunit-vaccinated or inactivated-vaccinated piglets with homologous virulent strains did not induce diarrhea, except in one or two piglets, which had mild diarrhea. Immunization with the bivalent subunit vaccine and inactivated vaccine also alleviated the microscopic lesions in the intestinal tissues caused by the challenge with the corresponding homologous virulent strain. However, all the piglets in the challenged group displayed mild to watery diarrhea and high levels of viral shedding, whereas the feces and intestines of the piglets in the bivalent subunit vaccine and inactivated vaccine groups had lower viral loads. In summary, our data show for the first time that a bivalent subunit vaccine combining VP4*P[7] and VP4*P[23] effectively protects piglets against the diarrhea caused by homologous virulent strains.IMPORTANCEPoRVs are the main causes of diarrhea in piglets worldwide. The multisegmented genome of PoRVs allows the reassortment of VP4 and VP7 genes from different RV species and strains. The P[7] and P[23] are the predominant genotypes circulating in pig farms, but no vaccine is available at present in China. Subunit vaccines, as nonreplicating vaccines, are an option to cope with variable genotypes. Here, we have developed a bivalent subunit candidate vaccine based on a truncated VP4 protein, which induced robust humoral and cellular immune responses and protected piglets against challenge with homologous PoRV. It also appears to be safe. These data show that the truncated VP4-protein-based subunit vaccine is a promising candidate for the prevention of PoRV diarrhea.

Available evidence on the co-administration of the four-component meningococcal B vaccine (4CMenB) with three vaccines at the same visit among pediatric individuals.

Vaccine co-administration is a useful strategy for improving vaccine coverage and adherence. In Italy, an update to the national immunization program (NIP) in 2023 included recommendations for co-administration of pediatric vaccines, including the four-component vaccine for meningococcus B (4CMenB), pneumococcal conjugate vaccine (PCV), hexavalent vaccines, and oral rotavirus vaccines. Safety is a major concern when considering vaccine co-administration; therefore, a literature review of the available evidence on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines was performed. Of 763 publications screened, two studies were reviewed that reported safety data on 4CMenB co-administration with PCV, hexavalent/pentavalent, and rotavirus vaccines in infants aged 0-24 months. Overall, these studies supported that there were no significant safety signals when co-administering 4CMenB with PCV, hexavalent/pentavalent, and rotavirus vaccines, compared with individual vaccination. This review provides key insights for healthcare professionals on the tolerability of co-administering 4CMenB with routine vaccines.

Rotavirus vaccine dose-two dropout and its associated factors among children who received rotavirus vaccine dose-one in Sub-Saharan African countries: A multilevel analysis of the recent demographic and health survey.

Rotavirus is the most common cause of diarrhea in children worldwide. In 2016, rotavirus infection resulted in 258 173 300 episodes of diarrhea and 128 500 child deaths in the globe. The study aimed to assess the magnitude of Rotavirus vaccine dose-two dropout and associated factors among children who received rotavirus vaccine dose-one in sub-Saharan African countries. The appended and most recent demographic and health survey (DHS) dataset of 17 sub-Saharan African countries was used for data analysis. A total of 73,396 weighted samples were used. Factors associated with the outcome variable were considered significant if their p-values were ≤ .05 in the multilevel mixed-effect logistic regression model. The overall Rotavirus vaccine dose-two dropouts was 10.77% (95% CI 10.55%, 11.00%), which ranged from 2.77% in Rwanda to 37.67% in Uganda. Being younger, late birth order, having difficulty accessing health facilities, having no media exposure, having no work, having home delivery, having no antenatal follow-up, and having no postnatal checkup were factors significantly associated with the outcome variable. The overall Rotavirus vaccine dose-two dropout was higher in sub-Saharan African countries which implies that vaccine dropout is still a great issue in the region. Special attention should be given to those mothers who are young, who have no work, who give birth at home, who experienced difficulty in accessing health facilities, and late birth orders. Furthermore, targeted interventions should be considered for improving access and utilization of media, antenatal care, and postnatal care services.

Immunogenicity of RV1 and RV5 vaccines administered in standard and interchangeable mixed schedules: a randomized, double-blind, non-inferiority clinical trial in Mexican infants.

Introduction: Rotavirus-associated diarrheal diseases significantly burden healthcare systems, particularly affecting infants under five years. Both Rotarix™ (RV1) and RotaTeq™ (RV5) vaccines have been effective but have distinct application schedules and limited interchangeability data. This study aims to provide evidence on the immunogenicity, reactogenicity, and safety of mixed RV1-RV5 schedules compared to their standard counterparts. Methods: This randomized, double-blind study evaluated the non-inferiority in terms of immunogenicity of mixed rotavirus vaccine schedules compared to standard RV1 and RV5 schedules in a cohort of 1,498 healthy infants aged 6 to 10 weeks. Participants were randomly assigned to one of seven groups receiving various combinations of RV1, and RV5. Standard RV1 and RV5 schedules served as controls of immunogenicity, reactogenicity, and safety analysis. IgA antibody levels were measured from blood samples collected before the first dose and one month after the third dose. Non-inferiority was concluded if the reduction in seroresponse rate in the mixed schemes, compared to the standard highest responding scheme, did not exceed the non-inferiority margin of -0.10. Reactogenicity traits and adverse events were monitored for 30 days after each vaccination and analyzed on the entire cohort. Results: Out of the initial cohort, 1,365 infants completed the study. Immunogenicity analysis included 1,014 infants, considering IgA antibody titers ≥20 U/mL as seropositive. Mixed vaccine schedules demonstrated non-inferiority to standard schedules, with no significant differences in immunogenic response. Safety profiles were comparable across all groups, with no increased incidence of serious adverse events or intussusception. Conclusion: The study confirms that mixed rotavirus vaccine schedules are non-inferior to standard RV1 and RV5 regimens in terms of immunogenicity and safety. This finding supports the flexibility of rotavirus vaccination strategies, particularly in contexts of vaccine shortage or logistic constraints. These results contribute to the global effort to optimize rotavirus vaccination programs for broader and more effective pediatric coverage.Clinical trial registration: ClinicalTrials.gov, NCT02193061.

Changes in vaccine coverage and incidence of acute gastroenteritis and severe rotavirus gastroenteritis in children <5 years in Shibata City, Niigata Prefecture, Japan.

Rotavirus (RV) vaccines were first introduced in 2011 and adopted for universal vaccination in 2020 in Japan. However, the effectiveness of RV vaccines after being adopted for universal vaccination in 2020 has not been reported. Because of the easy accessibility of clinics in Japan, many children are not usually hospitalized for RV gastroenteritis (RVGE). Therefore, in order to evaluate the impact of the RV vaccine since 2008, we investigated the incidence of hospitalization for RVGE as well as the frequency of children aged < 5 years who received medical treatment for severe RVGE at clinics in Shibata City, Japan. The RV vaccine coverage rate was 94.0% (1,046/1,113) in Shibata City after universal vaccination in 2020; this was a significant increase from previous rates. The incidence per 1000 person - years for RVGE hospitalization and severe RVGE at clinics were significantly higher among children aged < 3 years than in previous time periods. The incidence in children with all acute gastroenteritis (AGE) decreased significantly after universal vaccination during the COVID-19 pandemic. The proportion of severe RVGE among all AGE cases also decreased significantly after universal vaccination among children aged < 3 years (0.0%) and those aged 3-4 years (0.6%). There were significant differences in the distribution of RV genotypes isolated from the feces of children with RVGE between different eras divided by RV vaccination rates, especially G1P[8], which was the major genotype before it recently almost disappeared. Further studies are warranted to assess the impact of the COVID-19 pandemic.

Novel Universal Recombinant Rotavirus A Vaccine Candidate: Evaluation of Immunological Properties.

Rotavirus infection is a leading cause of severe dehydrating gastroenteritis in children under 5 years of age. Although rotavirus-associated mortality has decreased considerably because of the introduction of the worldwide rotavirus vaccination, the global burden of rotavirus-associated gastroenteritis remains high. Current vaccines have a number of disadvantages; therefore, there is a need for innovative approaches in rotavirus vaccine development. In the current study, a universal recombinant rotavirus antigen (URRA) for a novel recombinant vaccine candidate against rotavirus A was obtained and characterised. This antigen included sequences of the VP8* subunit of rotavirus spike protein VP4. For the URRA, for the first time, two approaches were implemented simultaneously-the application of a highly conserved neutralising epitope and the use of the consensus of the extended protein's fragment. The recognition of URRA by antisera to patient-derived field rotavirus isolates was proven. Plant virus-based spherical particles (SPs), a novel, effective and safe adjuvant, considerably enhanced the immunogenicity of the URRA in a mouse model. Given these facts, a URRA + SPs vaccine candidate is regarded as a prospective basis for a universal vaccine against rotavirus.

Correlates of immune protection against human rotaviruses: natural infection and vaccination.

Species A rotaviruses are the leading viral cause of acute gastroenteritis in children under 5 years of age worldwide. Despite progress in the characterization of the pathogenesis and immunology of rotavirus-induced gastroenteritis, correlates of protection (CoPs) in the course of either natural infection or vaccine-induced immunity are not fully understood. There are numerous factors such as serological responses (IgA and IgG), the presence of maternal antibodies (Abs) in breast milk, changes in the intestinal microbiome, and rotavirus structural and non-structural proteins that contribute to the outcome of the CoP. Indeed, while an intestinal IgA response and its surrogate, the serum IgA level, are suggested as the principal CoPs for oral rotavirus vaccines, the IgG level is more likely to be a CoP for parenteral non-replicating rotavirus vaccines. Integrating clinical and immunological data will be instrumental in improving rotavirus vaccine efficacy, especially in low- and middle-income countries, where vaccine efficacy is significantly lower than in high-income countries. Further knowledge on CoPs against rotavirus disease will be helpful for next-generation vaccine development. Herein, available data and literature on interacting components and proposed CoPs against human rotavirus disease are reviewed, and limitations and gaps in our knowledge in this area are discussed.

Production of OSU G5P[7] Porcine Rotavirus Expressing a Fluorescent Reporter via Reverse Genetics.

Rotaviruses are a significant cause of severe, potentially life-threatening gastroenteritis in infants and the young of many economically important animals. Although vaccines against porcine rotavirus exist, both live oral and inactivated, their effectiveness in preventing gastroenteritis is less than ideal. Thus, there is a need for the development of new generations of porcine rotavirus vaccines. The Ohio State University (OSU) rotavirus strain represents a Rotavirus A species with a G5P[7] genotype, the genotype most frequently associated with rotavirus disease in piglets. Using complete genome sequences that were determined via Nanopore sequencing, we developed a robust reverse genetics system enabling the recovery of recombinant (r)OSU rotavirus. Although rOSU grew to high titers (~107 plaque-forming units/mL), its growth kinetics were modestly decreased in comparison to the laboratory-adapted OSU virus. The reverse genetics system was used to generate the rOSU rotavirus, which served as an expression vector for a foreign protein. Specifically, by engineering a fused NSP3-2A-UnaG open reading frame into the segment 7 RNA, we produced a genetically stable rOSU virus that expressed the fluorescent UnaG protein as a functional separate product. Together, these findings raise the possibility of producing improved live oral porcine rotavirus vaccines through reverse-genetics-based modification or combination porcine rotavirus vaccines that can express neutralizing antigens for other porcine enteric diseases.

A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.

This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

Rates and determinants of Rotavirus vaccine uptake among children in Italy: a cross-sectional study within the 2022 OBVIOUS* project.

INTRODUCTION: The World Health Organization defines rotavirus as among the most severe causes of viral gastroenteritis affecting children under 5 year old. Italy and other European countries do not release disaggregated data on rotavirus vaccination coverage. This study aimed to assess the uptake and drivers of rotavirus vaccination in Italy. METHODS: We administered a survey to 10,000 Italian citizens recruited via an online panel and proportionate to key demographic strata. We examined rotavirus vaccine uptake among parents whose youngest child was aged 6 weeks to 4 years, their sociodemographic characteristics, their beliefs about vaccine administration, and who recommended the rotavirus vaccination. RESULTS: A total of 711 respondents met the inclusion criteria for the rotavirus vaccine questionnaire. The uptake was estimated at 60.3% nationwide (66.4% among mothers and 50.2% among fathers). Being a mother and living in cities/suburbs was significantly associated with a higher likelihood of vaccine uptake, while fathers were more likely to be uncertain of their children's vaccine status. Living in Central Italy and having friends/relatives opposed to vaccination were found to be significantly associated with a lower likelihood of vaccine uptake, while parents' education level and children's demographics were not found to correlate with any outcomes. In 90.3% of cases, the rotavirus vaccination was recalled as being recommended by a paediatrician. CONCLUSIONS: Consistent collection of behavioural preferences and socioeconomic characteristics of recipients of rotavirus vaccine campaigns, their epidemiological information, cost-benefit, and national policy data are crucial for designing effective vaccination strategies in Italy and other European countries with similar social profiles to reach the target uptake.

Post-marketing surveillance of intussusception after Rotarix administration in Afghanistan, 2018-2022.

BACKGROUND: In January 2018, Afghanistan introduced the monovalent oral rotavirus vaccine (Rotarix) nationwide, administered as a 2-dose series at six and ten weeks of age. We describe characteristics of intussusception cases and assess potential intussusception risk associated with Rotarix vaccination in Afghan infants. METHODS: Multi-center prospective active hospital-based surveillance for intussusception was conducted from May 2018 to March 2022 in four sentinel sites in Afghanistan. We applied the Brighton Level 1 criteria for intussusception and verified vaccination status by reviewing vaccine cards. We used the self-controlled case series (SCCS) methodology to compare intussusception incidence in the 1 to 21 days after each dose of Rotarix vaccination against non-risk periods. RESULTS: A total of 468 intussusception cases were identified in infants under 12 months, with 264 cases aged between 28 and 245 days having confirmed vaccination status contributing to the SCCS analysis. Most case-patients (98 %) required surgery for treatment, and over half (59 %) of those who underwent surgery required intestinal resection. Nineteen (7 %) case-patients died. Eighty-six percent of case-patients received the first dose of Rotarix, and 69 % received the second dose before intussusception symptom onset. There was no increased risk of intussusception in the 1-7 days (relative incidence: 0.9, 95 % CI: 0.1, 7.5), 8-21 days (1.3, 95 % CI: 0.4, 4.2), or 1-21 days (1.1, 95 % CI: 0.4, 3.4) following receipt of the first dose or in the 1-7 days (0.2, 95 % CI: 0.3, 1.8), 8-21 days (0.7, 95 % CI: 0.3, 1.5), or 1-21 days (0.6, 95 % CI: 0.3, 1.2) following the second dose. CONCLUSION: Rotarix vaccination was not associated with an increased intussusception risk, supporting its continued use in Afghanistan's immunization program. However, there was a high level of death and resection due to intussusception among Afghan infants.

Resurgent rotavirus diarrhoea outbreak five years after introduction of rotavirus vaccine in Botswana, 2018.

INTRODUCTION: Botswana had a resurgent diarrhea outbreak in 2018, mainly affecting children under five years old. Botswana introduced rotavirus vaccine (RotarixTM) into the national immunization programme in July 2012. Official rotavirus vaccine coverage estimates averaged 77.2% over the five years following introduction. MATERIALS AND METHODS: The outbreak was investigated using multiple data sources, including stool laboratory testing, immunization data review, water assessment, and vaccine storage assessment. We reviewed official reports of the routine immunization data from 2013 to 2017 and compared district-level rotavirus vaccine coverage with district-level attack rates during the outbreak. RESULTS: During the outbreak, a total of 228 stool samples were tested at the national health laboratory and 152 (67%) of the specimens were positive for rotavirus. A portion of adequate samples (80) were selected for referral to the Regional Reference Lab. The laboratory testing of 80 samples at the Regional Reference Laboratory in South Africa showed that 91% of the stool samples were positive for rotavirus, and the dominant strain 47/80 (58.7%) was G3P[8]. The immunization data showed that rotavirus vaccine coverage varied widely among districts, and there was no correlation between districts with high attack rates and those with low immunization coverage. Water assessment showed that some water sources were contaminated with E Coli. There was no problem with vaccine storage. CONCLUSION: The outbreak was caused by rotavirus G3P[8], a strain that was not common in the country prior to the outbreak. Despite the significant pressure and anxiety that outbreaks cause, the number of diarrhea cases and deaths were less compared to pre-vaccine era due to the impact of vaccination. This highlights the need for continuous implementation of high impact child survival interventions.

Understanding rapid implementation from discovery to scale: Rwanda's implementation of rotavirus vaccines and PMTCT in the quest to reduce under-5 mortality.

BACKGROUND: Over the last eight decades, many evidence-based interventions (EBIs) have been developed to reduce amenable under-5 mortality (U5M). Implementation research can help reduce the lag between discovery and delivery, including as new EBIs emerge, or as existing ones are adapted based on new research. Rwanda was the first low-income African country to implement the rotavirus vaccine (RTV) and also adopted Option B+ for effective prevention of mother-to-child transmission (PMTCT) before the World Health Organization's (WHO) recommendation. We use implementation research to identify contextual factors and strategies associated with Rwanda's rapid uptake of these two EBIs developed or adapted during the study period. METHODS: We conducted a mixed methods case study informed by a hybrid implementation research framework to understand how Rwanda outperformed regional and economic peers in reducing U5M, focusing on the implementation of health system-delivered EBIs. The research included review of existing literature and data, and key informant interviews to identify implementation strategies and contextual factors that influenced implementation outcomes. We extracted relevant results from the broader case study and used convergent methods to understand successes and challenges of implementation of RTV, a newly introduced EBI, and PMTCT, an adapted EBI reflecting new research. RESULTS: We found several cross-cutting strategies that supported the rapid uptake and implementation of PMTCT, RTV, and leveraging facilitating contextual factors and identifying and addressing challenging ones. Key implementation strategies included community and stakeholder involvement and education, leveraging of in-country research capacity to drive adoption and adaptation, coordination of donors and implementing partners, data audit and feedback of coverage, a focus on equity, and integration into pre-existing systems, including community health workers and primary care. The availability of donor funding, culture of evidence-based decision-making, preexisting accountability systems, and rapid adoption of innovation were facilitating contextual factors. CONCLUSION: Implementation strategies which are generalizable to other settings were key to success in rapidly achieving high acceptability and coverage of both a new and an evolving EBI. Choosing strategies which leverage their facilitating factors and address barriers are important for other countries working to accelerate uptake of new EBIs and implement needed adaptations based on emerging evidence.

Literature review to identify evidence of secondary transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains to unvaccinated subjects.

BACKGROUND: Rotavirus is the leading cause of severe diarrhea in infants and young children. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of pentavalent human-bovine reassortant rotavirus vaccine (RV5) strains leading to clinical disease was not well evaluated in the pivotal clinical trials, and only a few case reports have been described in the literature. METHODS: We performed a systematic literature review to investigate secondary transmission of RV5 strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers, and other resources (i.e., conference papers with full text) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles based on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 strain transmission as outcomes. Other study or publication types were excluded, such as pre-clinical studies, interventional studies and case reports. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used, and study quality was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess the risk of bias. RESULTS: The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of the NOS or JBI checklist, respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms, but all symptoms were attributed to other clinical conditions. CONCLUSIONS: We found no evidence of horizontal transmission of RV5 strains to unvaccinated infants in a context of a limited amount and the descriptive nature of the identified studies.

Safety, Immunogenicity, and Mechanism of a Rotavirus mRNA-LNP Vaccine in Mice.

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5' untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. Mice received three injections in 21 d intervals. IgG antibodies, neutralizing antibodies, cellular immunity, and gene expression from peripheral blood mononuclear cells were evaluated. Significant differences in levels of IgG antibodies were not observed in groups with adjuvant but were observed in groups without adjuvant. The vaccine without adjuvant induced the highest antibody titers after intramuscular injection. The vaccine elicited a potent antiviral immune response characterized by antiviral clusters of differentiation CD8+ T cells. VP7-mRNA induced interferon-γ secretion to mediate cellular immune responses. Chemokine-mediated signaling pathways and immune response were activated by VP7-mRNA vaccine injection. The mRNA LNP vaccine will require testing for protective efficacy, and it is an option for preventing rotavirus infection.

Genetic Profile of Rotavirus Type A in Children under 5 Years Old in Africa: A Systematic Review of Prevalence.

Human type A rotavirus (RV-A) is world-recognized as the major pathogen causing viral gastroenteritis in children under 5 years of age. The literature indicates a substantial increase in the diversity of rotavirus strains across continents, especially in Africa, which can pose significant challenges including an increase of disease burden and a reduction of vaccines' effectiveness. However, few studies have mapped the variety of circulating virus strains in different regions, which may hamper decisions on epidemiological surveillance and preventive public health measures. Thus, our aim was to compile the most updated available evidence on the genetic profile of RV-A among children in Africa and determine the prevalence of different genotypes according to the geographical regions by means of a broad systematic review. Systematic searches were performed in PubMed, Scopus, Web of Science, and Scielo without language, time limits, or geographical restrictions within the African continent. We selected full-text peer-reviewed articles assessing the genetic profile (i.e., genotyping) of RV-A in children up to 5 years old in Africa. Overall, 682 records were retrieved, resulting in 75 studies included for evidence synthesis. These studies were published between 1999 and 2022, were conducted in 28 countries from the five African regions, and 48% of the studies were carried out for 24 months or more. Most studies (n = 55; 73.3%) evaluated RV-A cases before the introduction of the vaccines, while around 20% of studies (n = 13) presented data after the vaccine approval in each country. Only seven (9.3%) studies compared evidence from both periods (pre- and post-vaccine introduction). Genotyping methods to assess RV-A varied between RT-PCR, nested or multiplex RT-PCR, testing only the most common P and G-types. We observed G1 and P[8] to be the most prevalent strains in Africa, with values around 31% and 43%, respectively. Yet if all the genotypes with the following highest prevalence were added ((G1 + G2, G3, G9) and (P[8] + P[6], P[4])), these figures would represent 80% and 99% of the total prevalence. The combination G1P[8] was the most reported in the studies (around 22%). This review study demonstrated an increased strain diversity in the past two decades, which could represent a challenge to the efficacy of the current vaccine.