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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 -
Human Vaccines & Immunotherapeutics Feb 2018There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil),... (Review)
Review
There are two internationally available WHO-prequalified oral rotavirus vaccines (Rotarix and RotaTeq), two rotavirus vaccines licensed in India (Rotavac and Rotasiil), one in China (Lanzhou lamb rotavirus vaccine) and one in Vietnam (Rotavin-M1), and several candidates in development. Rotavirus vaccination has been rolled out in Latin American countries and is beginning to be deployed in sub-Saharan African countries but middle- and low-income Asian countries have lagged behind in rotavirus vaccine introduction. We provide a mini-review of the leading newer-generation rotavirus vaccines and compare them with Rotarix and RotaTeq. We discuss how the development and future availability of newer-generation rotavirus vaccines that address the programmatic needs of poorer countries may help scale-up rotavirus vaccination where it is needed.
Topics: Drug Industry; Humans; Immunization Programs; Rotavirus Infections; Rotavirus Vaccines; World Health Organization
PubMed: 29135339
DOI: 10.1080/21645515.2017.1403705 -
BMJ Open Apr 2019Rotavirus infection accounts for 39% of under-five diarrhoeal deaths globally and 22% of these deaths occur in India. Introduction of rotavirus vaccine in a national...
INTRODUCTION
Rotavirus infection accounts for 39% of under-five diarrhoeal deaths globally and 22% of these deaths occur in India. Introduction of rotavirus vaccine in a national immunisation programme is considered to be the most effective intervention in preventing severe rotavirus disease. In 2016, India introduced an indigenous rotavirus vaccine (Rotavac) into the Universal Immunisation Programme in a phased manner. This paper describes the protocol for surveillance to monitor the performance of rotavirus vaccine following its introduction into the routine childhood immunisation programme.
METHODS
An active surveillance system was established to identify acute gastroenteritis cases among children less than 5 years of age. For all children enrolled at sentinel sites, case reporting forms are completed and a copy of vaccination record and a stool specimen obtained. The forms and specimens are sent to the referral laboratory for data entry, analysis, testing and storage. Data from sentinel sites in states that have introduced rotavirus vaccine into their routine immunisation schedule will be used to determine rotavirus vaccine impact and effectiveness.
ETHICS AND DISSEMINATION
The Institutional Review Board of Christian Medical College, Vellore, and all the site institutional ethics committees approved the project. Results will be disseminated in peer-reviewed journals and with stakeholders of the universal immunisation programme in India.
Topics: Child, Preschool; Diarrhea; Female; Health Care Surveys; Humans; Immunization Programs; India; Infant; Infant, Newborn; Male; Program Evaluation; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Sentinel Surveillance; Vaccination
PubMed: 31028037
DOI: 10.1136/bmjopen-2018-024840 -
Human Vaccines & Immunotherapeutics Jun 2021In the decade since oral rotavirus vaccines (ORV) were recommended by the World Health Organization for universal inclusion in all national immunization programs,... (Review)
Review
In the decade since oral rotavirus vaccines (ORV) were recommended by the World Health Organization for universal inclusion in all national immunization programs, significant yet incomplete progress has been made toward reducing the burden of rotavirus in low- to middle-income countries (LMIC). ORVs continue to demonstrate effectiveness and impact in LMIC, yet numerous factors hinder optimal performance and evaluation of these vaccines. This review will provide an update on ORV performance in LMIC, the increasing body of literature regarding factors that affect ORV response, and the status of newer and next-generation rotavirus vaccines as of early 2020. Fully closing the gap in rotavirus prevention between LMIC and high-income countries will likely require a multifaceted approach accounting for biological and methodological challenges and evaluation and roll-out of newer and next-generation vaccines.
Topics: Developing Countries; Humans; Immunization Programs; Rotavirus; Rotavirus Infections; Rotavirus Vaccines
PubMed: 33327868
DOI: 10.1080/21645515.2020.1844525 -
Vaccine Oct 2021The pre-existing partner network created in India for the delivery of polio vaccines was initially used to eradicate polio and later on embedded in the health systems... (Review)
Review
BACKGROUND
The pre-existing partner network created in India for the delivery of polio vaccines was initially used to eradicate polio and later on embedded in the health systems network to promote routine immunization and other health interventions efficiently. The experience from this network offered lessons for strengthening the health care systems and provided a well-established network that could be utilized for other vaccine initiatives. It has also been established that successful partnerships between a broad range of stakeholders provide support, strengthen the health system, and accelerate vaccine innovation, introduction, access, logistics, and communication support. However, beyond polio eradication, there have not been too many documented success stories of vaccine introduction, which could be replicated in other new vaccine introductions and allied health initiatives. The authors have reviewed the successful and time-bound introduction of rotavirus vaccine (RVV) in India in the present article.
METHODS
The review was conducted based on a partnership framework which analysed multiple factors-partnership prerequisites, partnership model, partnership process, and partnership performance, thereby providing a comprehensive insight into the successful utilization of partnership networks for rotavirus vaccine introduction under the Universal Immunization Program in India.
RESULTS & CONCLUSION
The review also highlights the role of a lead agency in creating a fertile ground for lush, efficient, and effective partnerships amongst different stakeholders. The already existing RVV partnership framework reviewed by the authors can be successfully utilized for future new vaccine introductions.
Topics: Humans; Immunization Programs; India; Poliomyelitis; Retrospective Studies; Rotavirus Vaccines; Vaccination
PubMed: 34538521
DOI: 10.1016/j.vaccine.2021.09.014 -
Indian Journal of Medical Microbiology Oct 2006Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several... (Review)
Review
Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licensed vaccines are either animal-human re-assortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.
Topics: Animals; Cattle; Clinical Trials as Topic; Drug Design; Humans; Intussusception; Reassortant Viruses; Rotavirus; Rotavirus Infections; Rotavirus Vaccines
PubMed: 17185842
DOI: 10.4103/0255-0857.29382 -
Expert Review of Vaccines Jun 2020Rotavirus is the leading cause of acute diarrhea among children <5 years worldwide. As all children are equally susceptible to infection and disease development,... (Review)
Review
INTRODUCTION
Rotavirus is the leading cause of acute diarrhea among children <5 years worldwide. As all children are equally susceptible to infection and disease development, rotavirus vaccination programs are the best upstream approach to preventing rotavirus disease, and the subsequent risk of hospitalization or death.
AREAS COVERED
We provide an overview of global rotavirus vaccine policy, summarize the burden of rotavirus disease in developing countries, review data on the effectiveness, impact, safety, and the cost-effectiveness of rotavirus vaccination programs, and identify areas for further research and improvement.
EXPERT OPINION
Rotavirus vaccines continue to be an effective, safe, and cost-effective solution to preventing rotavirus disease. As two new rotavirus vaccines enter the market (Rotasiil and Rotavac) and Asian countries continue to introduce rotavirus vaccines into their national immunization programs, documenting vaccine safety, effectiveness, and impact in these settings will be paramount.
Topics: Acute Disease; Child, Preschool; Cost-Benefit Analysis; Developing Countries; Diarrhea; Health Policy; Humans; Immunization Programs; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 32543239
DOI: 10.1080/14760584.2020.1775079 -
Uirusu Jun 2012Since the presentation of the clinical trial reports showing the excellent efficacy and safety of the two human rotavirus vaccines (Rotarix and RotaTeq), the human... (Review)
Review
Since the presentation of the clinical trial reports showing the excellent efficacy and safety of the two human rotavirus vaccines (Rotarix and RotaTeq), the human rotavirus vaccines have received worldwide attention. The two vaccines have been approved in more than 100 countries, and were included in routine immunization schedule in about 30 countries. The effectiveness of the two vaccines exceeded our expectations, and severe rotavirus gastroenteritis cases have been greatly reduced. Also in Japan, administration of Rotarix started just last November, and RotaTeq will be also started soon. On this occasion, composition, characteristics, and effectiveness of these vaccines are described, and some points relating to the vaccination such as intussusception, cross protection, shedding and so on are also discussed.
Topics: Animals; Clinical Trials as Topic; Colonic Diseases; Gastroenteritis; Humans; Intussusception; Mice; Rotavirus Infections; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 23189828
DOI: 10.2222/jsv.62.87 -
Human Vaccines & Immunotherapeutics 2014Rotavirus is the leading cause of severe diarrhea among children<5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many... (Review)
Review
Rotavirus is the leading cause of severe diarrhea among children<5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction.
Topics: Diarrhea; Drug Discovery; Humans; Rotavirus Infections; Rotavirus Vaccines
PubMed: 24755452
DOI: 10.4161/hv.28857 -
Vaccine Aug 2022Since the introduction of live-attenuated rotavirus vaccines in Belgium in 2006, surveillance has routinely detected rotavirus vaccine-derived strains. However, their...
Since the introduction of live-attenuated rotavirus vaccines in Belgium in 2006, surveillance has routinely detected rotavirus vaccine-derived strains. However, their genomic landscape and potential role in gastroenteritis have not been thoroughly investigated. We compared VP7 and VP4 nucleotide sequences obtained from rotavirus surveillance with the Rotarix vaccine sequence. As a result, we identified 80 vaccine-derived strains in 5125 rotavirus-positive infants with gastroenteritis from 2007 to 2018. Using both viral metagenomics and reverse transcription qPCR, we evaluated the vaccine strains and screened for co-infecting enteropathogens. Among the 45 patients with known vaccination status, 39 were vaccinated and 87% received the vaccine less than a month before the gastroenteritis episode. Reconstruction of 30 near complete vaccine-derived genomes revealed 0-11 mutations per genome, with 88% of them being non-synonymous. This, in combination with several shared amino acid changes among strains, pointed at selection of minor variant(s) present in the vaccine. We also found that some of these substitutions were true revertants (e.g., F167L on VP4, and I45T on NSP4). Finally, co-infections with known (e.g., Clostridioides difficile and norovirus) and divergent or emerging (e.g., human parechovirus A1, salivirus A2) pathogens were detected, and we estimated that 35% of the infants likely had gastroenteritis due to a 'non-rotavirus' cause. Conversely, we could not rule out the vaccine-derived gastroenteritis in over half of the cases. Continued studies inspecting reversion to pathogenicity should monitor the long-time safety of live-attenuated rotavirus vaccines. All in all, the complementary approach with NGS and qPCR provided a better understanding of rotavirus vaccine strain evolution in the Belgian population and epidemiology of co-infecting enteropathogens in suspected rotavirus vaccine-derived gastroenteritis cases.
Topics: Antigens, Viral; Belgium; Gastroenteritis; Genotype; Humans; Infant; Mutation; Phylogeny; Rotavirus; Rotavirus Infections; Rotavirus Vaccines
PubMed: 35871871
DOI: 10.1016/j.vaccine.2022.06.082