-
Vaccine Jul 2021ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
ROTAVIN-M1® (licensed, frozen vaccine) and ROTAVIN (second-generation, liquid candidate vaccine) are two rotavirus vaccine formulations developed from a live attenuated G1P8 (KH0118) strain by Center for Research and Production of Vaccines and Biologicals (POLYVAC), Vietnam. This study compared the safety and immunogenicity of these two formulations.
METHODS
A Phase 3, randomized, partially double-blinded, active-controlled study was conducted in healthy infants aged 60-91 days in Vietnam. Infants received two doses of ROTAVIN or ROTAVIN-M1 in a ratio of 2:1 with an interval of 8 weeks. Solicited reactions were collected for 7 days after each vaccination. Blood samples were collected pre-vaccination and 4 weeks after the second vaccination in a subset of infants. Non-inferiority criteria required that the lower bound of 95% confidence intervals (CIs) of the post-vaccination anti-rotavirus IgA GMC (Geometric Mean Concentration) ratio of ROTAVIN/ROTAVIN-M1 should be >0.5. A co-primary objective was to compare the safety of the two vaccines in terms of solicited reactions.
RESULTS
A total of 825 infants were enrolled. The post-vaccination GMC was 48.25 (95% CI: 40.59, 57.37) in the ROTAVIN group and 35.04 (95% CI: 27.34, 44.91) in the ROTAVIN-M1 group with an IgA GMC ratio of 1.38 (95% CI: 1.02, 1.86) thus meeting the pre-set criteria for non-inferiority. A total of 605 solicited reactions were reported in 297 (36.0%) participants with 35.4% in the ROTAVIN group and 37.2% in the ROTAVIN-M1 group. There were no cases of intussusception or death reported in the study.
CONCLUSIONS
Based on the data generated, it can be concluded that ROTAVIN is immunologically non-inferior and has similar safety profile to ROTAVIN-M1 when administered to infants in a two-dose schedule. Therefore, it can be considered as a more suitable option for programmatic use to prevent rotavirus diarrhoea in Vietnam and the Mekong region.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov identifier: NCT03703336, October 11, 2018.
Topics: Antibodies, Viral; Asian People; Humans; Immunogenicity, Vaccine; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated; Vietnam
PubMed: 34218961
DOI: 10.1016/j.vaccine.2021.06.056 -
Pediatrics Oct 2019Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia,...
BACKGROUND
Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia, from that time. In 2017, New South Wales experienced a large outbreak of rotavirus gastroenteritis. We examined epidemiology, genotypic profiles, and vaccine effectiveness (VE) among cases.
METHODS
Laboratory-confirmed cases of rotavirus notified in New South Wales between January 1, 2010 and December 31, 2017 were analyzed. VE was estimated in children via a case-control analysis. Specimens from a sample of hospitalized case patients were genotyped and analyzed.
RESULTS
In 2017, 2319 rotavirus cases were reported, representing a 3.1-fold increase on the 2016 notification rate. The highest rate was among children aged <2 years. For notified cases in 2017, 2-dose VE estimates were 88.4%, 83.7%, and 78.7% in those aged 6 to 11 months, 1 to 3 years, and 4 to 9 years, respectively. VE was significantly reduced from 89.5% within 1 year of vaccination to 77.0% at 5 to 10 years postvaccination. Equinelike G3P[8] (48%) and G8P[8] (23%) were identified as the most common genotypes in case patients aged ≥6 months.
CONCLUSIONS
Rotarix is highly effective at preventing laboratory-confirmed rotavirus in Australia, especially in infants aged 6 to 11 months. Reduced VE in older age groups and over time suggests waning protection, possibly related to the absence of subclinical immune boosting from continuously circulating virus. G8 genotypes have not been common in Australia, and their emergence, along with equinelike G3P[8], may be related to vaccine-induced selective pressure; however, further strain-specific VE studies are needed.
Topics: Adolescent; Adult; Age Distribution; Age Factors; Aged; Aged, 80 and over; Case-Control Studies; Child; Child, Preschool; Disease Notification; Disease Outbreaks; Female; Gastroenteritis; Genotype; Humans; Immunization Programs; Immunogenicity, Vaccine; Infant; Male; Middle Aged; New South Wales; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Treatment Outcome; Vaccines, Attenuated; Young Adult
PubMed: 31530719
DOI: 10.1542/peds.2019-1024 -
The Journal of Infectious Diseases Sep 2020Although 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... (Review)
Review
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. Furthermore, rotavirus infection has been shown to modify T1D risk in T1D-prone mice. However, research into associations of rotavirus infections with T1D development in humans have yielded mixed findings and suggested interactions with age and diet. As global availability of rotavirus vaccines increases, recent studies have assessed whether rotavirus vaccination modifies T1D development, finding null or protective associations. Overall, evidence to date suggests a possible triggering relationship between some wild-type rotavirus infections and T1D, but the potential effect of rotavirus vaccination remains unclear.
Topics: Animals; Diabetes Mellitus, Type 1; Gastroenteritis; Humans; Mice; Mice, Inbred NOD; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 32249284
DOI: 10.1093/infdis/jiaa168 -
Reviews in Medical Virology Jan 2022Group A rotaviruses (RVAs) are the leading cause of gastroenteritis, causing 0.2 million deaths and several million hospitalisations globally each year. Four rotavirus... (Review)
Review
Group A rotaviruses (RVAs) are the leading cause of gastroenteritis, causing 0.2 million deaths and several million hospitalisations globally each year. Four rotavirus vaccines (Rotarix , RotaTeq , Rotavac and ROTASIIL ) have been pre-qualified by the World Health Organization (WHO), but the two newly pre-qualified vaccines (Rotavac and ROTASIIL ) are currently only in use in Palestine and India, respectively. In 2009, WHO strongly proposed that rotavirus vaccines be included in the routine vaccination schedule of all countries around the world. By the end of 2019, a total of 108 countries had administered rotavirus vaccines, and 10 countries have currently been approved by Gavi for the introduction of rotavirus vaccine in the near future. With 39% of global coverage, rotavirus vaccines have had a substantial effect on diarrhoeal morbidity and mortality in different geographical areas, although efficacy appears to be higher in high income settings. Due to the segmented RNA genome, the pattern of RVA genotypes in the human population is evolving through interspecies transmission and/or reassortment events for which the vaccine might be less effective in the future. However, despite the relative increase in some particular genotypes after rotavirus vaccine use, the overall efficacy of rotavirus mass vaccination worldwide has not been affected. Some of the challenges to improve the effect of current rotavirus vaccines can be solved in the future by new rotavirus vaccines and by vaccines currently in progress.
Topics: Gastroenteritis; Genetic Variation; Humans; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 34997676
DOI: 10.1002/rmv.2259 -
BMJ Global Health May 2021Vaccine licensure requires a very high safety standard and vaccines routinely used are very safe. Vaccine safety monitoring prelicensure and postlicensure enables... (Review)
Review
Vaccine licensure requires a very high safety standard and vaccines routinely used are very safe. Vaccine safety monitoring prelicensure and postlicensure enables continual assessment to ensure the benefits outweigh the risks and, when safety problems arise, they are quickly identified, characterised and further problems prevented when possible. We review five vaccine safety case studies: (1) dengue vaccine and enhanced dengue disease, (2) pandemic influenza vaccine and narcolepsy, (3) rotavirus vaccine and intussusception, (4) human papillomavirus vaccine and postural orthostatic tachycardia syndrome and complex regional pain syndrome, and (5) RTS,S/adjuvant system 01 malaria vaccine and meningitis, cerebral malaria, female mortality and rebound severe malaria. These case studies were selected because they are recent and varied in the vaccine safety challenges they elucidate. Bringing these case studies together, we develop lessons learned that can be useful for addressing some of the potential safety issues that will inevitably arise with new vaccines.
Topics: Female; Humans; Malaria; Rotavirus Vaccines
PubMed: 34011502
DOI: 10.1136/bmjgh-2020-003814 -
Virologica Sinica Oct 2022A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live... (Randomized Controlled Trial)
Randomized Controlled Trial
A randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a hexavalent live human-bovine reassortant rotavirus vaccine (HRV) against rotavirus gastroenteritis (RVGE). A total of 6400 participants aged 6-12 weeks were enrolled and randomly assigned to either HRV (n = 3200) or placebo (n = 3200) group. All the subjects received three oral doses of vaccine four weeks apart. The vaccine efficacy (VE) against RVGE caused by rotavirus serotypes contained in HRV was evaluated from 14 days after three doses of administration up until the end of the second rotavirus season. VE against severe RVGE, VE against RVGE hospitalization caused by serotypes contained in HRV, and VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were also investigated. All adverse events (AEs) were collected for 30 days after each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. Our data showed that VE against RVGE caused by serotypes contained in HRV was 69.21% (95%CI: 53.31-79.69). VE against severe RVGE and RVGE hospitalization caused by serotypes contained in HRV were 91.36% (95%CI: 78.45-96.53) and 89.21% (95%CI: 64.51-96.72) respectively. VE against RVGE, severe RVGE, and RVGE hospitalization caused by natural infection of any serotype of rotavirus were 62.88% (95%CI: 49.11-72.92), 85.51% (95%CI: 72.74-92.30) and 83.68% (95%CI: 61.34-93.11). Incidences of AEs from the first dose to one month post the third dose in HRV and placebo groups were comparable. There was no significant difference in incidences of SAEs in HRV and placebo groups. This study shows that this hexavalent reassortant rotavirus vaccine is an effective, well-tolerated, and safe vaccine for Chinese infants.
Topics: Administration, Oral; Animals; Cattle; China; Enterovirus Infections; Gastroenteritis; Humans; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination; Vaccines, Attenuated; Vaccines, Combined
PubMed: 35926726
DOI: 10.1016/j.virs.2022.07.011 -
Scientific Reports Dec 2023The study aims to determine Rotavirus genotypes between 2013 and 2018 during implementation of ROTARIX vaccine in Tanzania. The analysis of surveillance data obtained...
The study aims to determine Rotavirus genotypes between 2013 and 2018 during implementation of ROTARIX vaccine in Tanzania. The analysis of surveillance data obtained between 2013 and 2018 was done to determine circulating genotypes after introduction of Rotarix vaccine. From 2013 to 2018, a total of 10,557 samples were collected and screened for Rotavirus using an enzyme immunoassay. A significant decrease in Rotavirus positivity (29.3% to 17.8%) from 2013 to 2018 (OR 0.830, 95% CI 0.803-0.857, P < 0.001) was observed. A total of 766 randomly selected Rotavirus positive samples were genotyped. Between 2013 and 2018, a total of 18 Rotavirus genotypes were detected with G1P [8] being the most prevalent. The G1P [8] strain was found to decrease from 72.3% in 2015 to 13.5% in 2018 while the G9P [4] strain increased from 1 to 67.7% in the same years. G2P [4] was found to decrease from 59.7% in 2013 to 6.8% in 2018 while G3P [6] decreased from 11.2% in 2014 to 4.1% in 2018. The data has clearly demonstrated that ROTARIX vaccine has provided protection to varieties of the wild-type Rotavirus strains. Continuous surveillance is needed to monitor the circulation of Rotavirus strains during this era of vaccine implementation.
Topics: Humans; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Tanzania; Genotype; Feces
PubMed: 38066194
DOI: 10.1038/s41598-023-49350-4 -
The Journal of Infectious Diseases Jun 2022Rotavirus is a major cause of gastroenteritis in children <5 years of age. The disease burden in older children, adults, and the elderly is underappreciated. This...
BACKGROUND
Rotavirus is a major cause of gastroenteritis in children <5 years of age. The disease burden in older children, adults, and the elderly is underappreciated. This study describes rotavirus disease and genotypic diversity in the Australian population comprising children ≥5 years of age and adults.
METHODS
Rotavirus positive fecal samples were collected from laboratories Australia-wide participating in the Australian Rotavirus Surveillance Program between 2010 and 2018. Rotavirus samples were genotyped using a heminested multiplex reverse-transcription polymerase chain reaction. Notification data from the National Notifiable Diseases Surveillance System were also analyzed.
RESULTS
Rotavirus disease was highest in children aged 5-9 years and adults ≥85 years. G2P[4] was the dominant genotype in the population ≥5 years of age. Genotype distribution fluctuated annually and genotypic diversity varied among different age groups. Geographical differences in genotype distribution were observed based on the rotavirus vaccine administered to infants <1 year of age.
CONCLUSIONS
This study revealed a substantial burden of rotavirus disease in the population ≥5 years of age, particularly in children 5-9 years and the elderly. This study highlights the continued need for rotavirus surveillance across the population, despite the implementation of efficacious vaccines.
Topics: Adult; Aged; Australia; Child; Child, Preschool; Feces; Genotype; Humans; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines
PubMed: 32692812
DOI: 10.1093/infdis/jiaa430 -
Viruses Jan 2024Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of...
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.
Topics: Child; Animals; Mice; Humans; Child, Preschool; Rotavirus; Rotavirus Vaccines; mRNA Vaccines; Rotavirus Infections; RNA, Messenger; CD8-Positive T-Lymphocytes; Leukocytes, Mononuclear; Antibodies, Viral; Capsid Proteins; Adjuvants, Immunologic; Vaccines, Attenuated; Immunoglobulin G
PubMed: 38399987
DOI: 10.3390/v16020211 -
Vaccine Jul 2021Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks...
BACKGROUND
Rotavirus vaccines are effective in preventing severe rotavirus. Haiti introduced 2-dose monovalent (G1P[8]) rotavirus vaccine recommended for infants at 6 and 10 weeks of age in 2014. We calculated the effectiveness of rotavirus vaccine against hospitalization for acute gastroenteritis in Haiti.
METHODS
We enrolled children 6-59 months old admitted May 2014-September 2019 for acute watery diarrhea at any sentinel surveillance hospital. Stool was tested for rotavirus using enzyme immunoassay (EIA) and genotyped with multiplex one-step RT-PCR assay and Sanger sequencing for stratification by genotype. We used a case-negative design where cases were children positive for rotavirus and controls were negative for rotavirus. Only children eligible for vaccination were included and a child was considered vaccinated if vaccine was given ≥ 14 days before enrollment. We used unconditional logistic regression to calculate odds ratios and calculated 2-dose and 1-dose vaccine effectiveness (VE) as (1 - odds ratio) * 100.
RESULTS
We included 129 (19%) positive cases and 543 (81%) negative controls. Among cases, 77 (60%) were positive for equine-like G3P[8]. Two doses of rotavirus vaccine were 66% (95% CI: 44, 80) effective against hospitalizations due to any strain of rotavirus and 64% (95% CI: 33, 81) effective against hospitalizations due to the equine-like G3P[8] genotype.
CONCLUSIONS
These findings are comparable to other countries in the Americas region. To the best of our knowledge, this is the first VE estimate both against the equine-like G3P[8] genotype and from a Caribbean country. Overall, these results support rotavirus vaccine use and demonstrate the importance of complete vaccination.
Topics: Animals; Child; Child, Preschool; Feces; Genotype; Haiti; Horses; Hospitalization; Humans; Infant; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 34187708
DOI: 10.1016/j.vaccine.2021.06.055