Lamb Rotavirus Research Articles

VP8 Mosaic Nanoparticles Elicit Cross-Neutralizing Immune Responses and Provide Protection Against Heterotypic Rotavirus Challenge in Mice.

Group A rotaviruses (RVA) remain one of the dominant pathogens causing diarrhea in children under 5 years of age worldwide, despite a sharp decrease of RVA-associated diarrhea and mortality since the introduction of rotavirus vaccines. The decreased effectiveness of live attenuated rotavirus vaccines, coupled with the emergence of new rotavirus genotypes and the risk of cross-species virus transmission, underscores the necessity to develop more effective and broad-spectrum rotavirus vaccines. In this study, we utilized nanoparticles coupled with the SpyCatcher-SpyTag system to effectively display the truncated VP8-1 protein. The modular display of the monovalent VP8-1 proteins markedly increased the immunogenicity of VP8-1. Furthermore, the bivalent display of VP8-1 proteins from simian rotavirus SA11 and lamb rotavirus LLR on the same particle not only increased immunogenicity against homotypic antigens but also elicited robust heterotypic immune responses and conferred effective protection against a distant heterotypic rotavirus with sequence identities of only 62%-66% in an adult mouse model. Therefore, mosaic VP8 nanoparticles could be considered as a viable strategy for the development of the next-generation broad-spectrum rotavirus vaccine.

Effectiveness of Lanzhou Lamb Rotavirus Vaccine and RotaTeq Against Hospitalized Rotavirus Infections Among Children During 2020-2023 in Guangdong Province, China: A Test-Negative Case-Control Study.

The evidence regarding the effectiveness of Lanzhou Lamb Rotavirus Vaccine (LLR) and RotaTeq (RV5) against gastroenteritis (RVGE) caused by emerging genotypes in Chinese children remains limited. We conducted a test-negative case-control study using gastroenteritis surveillance data from four cities (2020-2023) in Guangdong Province, China. Children aged 2months to 5years hospitalized with acute gastroenteritis were enrolled. Cases were rotavirus-positive; controls were rotavirus-negative. Vaccine effectiveness (VE) was estimated using multivariable logistic regressions. Among 2650 children, 218 (8.2%) were rotavirus-positive, predominantly G8P[8]. Also, 1543 (58.23%) children were unvaccinated, while 632 (23.85%) and 475 (17.92%) received at least one dose of RV5 and LLR, respectively. Adjusted RV5 VE against any RVGE severity was 51.7% [95% confidence interval (CI) -58.1-85.3%]) for one dose, 37.6% (95% CI -58.5-75.4%) for two doses, and 64.1% (95% CI 38.0-79.2%) for three doses. For LLR, VE against any RVGE severity was 38.7% (95% CI 5.7-60.2%) for one dose, 74.6% (95% CI 35.3-90.0%) for two doses, and 58.8% (95% CI -217.6-94.6%) for three doses. Against severe RVGE, RV5 VE was 67.2% (95% CI -144.7-95.6%) for one dose, 74.0% (95% CI -92.1-96.5%) for two doses, and 86.6% (95% CI 56.8-95.9%) for three doses. For LLR, VE against severe RVGE was 57.7% (95% CI 20.3-77.6%) for one dose, 73.4% (95% CI 11.9-92.0%) for two doses, and -27.8% (95% CI -949.7-84.4%) for three doses. Both RV5 and LLR provided protection against RVGE, including the emerging G8P[8] genotype. Three doses of RV5 offered strong protection, while two doses of LLR also appeared to be an effective strategy against rotavirus infection.

Effectiveness of Pentavalent Rotavirus Vaccine in Shanghai, China: A Test-Negative Design Study

To evaluate vaccine effectiveness (VE) of a live oral pentavalent rotavirus vaccine (RotaTeq, RV5) among young children in Shanghai, China, via a test-negative design study. We consecutively recruited children visiting a tertiary children's hospital for acute diarrhea from November 2021 to February 2022. Information on clinical data and rotavirus vaccination was collected. Fresh fecal samples were obtained for rotavirus detection and genotyping. To evaluate VE of RV5 against rotavirus gastroenteritis among young children, unconditional logistic regression models were conducted to compare ORs for vaccination between rotavirus-positive cases and test-negative controls. A total of 390 eligible children with acute diarrhea were enrolled, including 45 (11.54%) rotavirus-positive cases and 345 (88.46%) test-negative controls. After excluding 4 cases (8.89%) and 55 controls (15.94%) who had received the Lanzhou lamb rotavirus vaccine, 41 cases (12.39%) and 290 controls (87.61%) were included for the evaluation of RV5 VE. After adjustment for potential confounders, the 3-dose RV5 vaccination showed 85% (95% CI, 50%-95%) VE against mild to moderate rotavirus gastroenteritis among children aged 14 weeks to≤4years and 97% (95% CI, 83%-100%) VE among children aged 14 weeks to≤2years with genotypes G8P8, G9P8, and G2P4 represented 78.95%, 18.42%, and 2.63% of circulation strains, respectively. A 3-dose vaccination of RV5 is highly protective against rotavirus gastroenteritis among young children in Shanghai. The G8P8 genotype prevailled in Shanghai after RV5 introduction.

Public health impact and cost-effectiveness of rotavirus vaccination in China: Comparison between private market provision and national immunization programs

ABSTRACT In China, progress to include the RV vaccine in the national immunization program (NIP) is slow. The only two vaccines, the Lanzhou lamb rotavirus vaccine (LLR) and Rotateq, are provided through the private market. This study aims to assess the health impact and cost-effectiveness of using three vaccines in the NIP, Rotateq, Rotarix, and LLR, compared to the status quo. A decision-tree Markov model was adopted to follow the 2019 birth cohort, and a societal perspective was used. Input parameters were based on the latest local data when possible. Outcomes included cases and deaths averted, quality-adjusted life years (QALYs) gained, and incremental cost-effectiveness ratios (ICER). Sensitivity analyses and scenario analyses to consider herd immunity and vaccine price reduction were performed. Including Rotateq in the NIP was projected to prevent 348 million RVGE cases (62.6% reduction) and 4251 deaths (72.6% reduction) compared to the status quo. Rotarix through the NIP would prevent 48.7% of cases and 63.2% of deaths, and LLR would avert 20.3% of cases and 22.4% of deaths. The ICERs per QALY gained were US$ 8833 for Rotateq through the NIP, US$ 9503 for Rotarix, and US$ 26,759 for LLR. In uncertainty analyses, the reduction of vaccine prices and the incorporation of herd immunity further improved the cost-effectiveness of the NIPs, especially Rotateq or Rotarix. In conclusion, introducing the RV vaccine in China’s NIP is expected to be cost-effective compared to the GDP per capita. Reducing vaccine prices and adopting vaccines with better efficacy would be the future focus.

Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children Younger Than 5 Years

Rotavirus vaccines have been introduced worldwide, and the clinical association of different rotavirus vaccines with reduction in rotavirus gastroenteritis (RVGE) after introduction are noteworthy. To evaluate the comparative benefit, risk, and immunogenicity of different rotavirus vaccines by synthesizing randomized clinical trials (RCTs) and observational studies. Relevant studies published in 4 databases: Embase, PubMed, the Cochrane Library, and Web of Science were searched until July 1, 2020, using search terms including "rotavirus" and "vaccin*." Randomized clinical trials and cohort and case-control studies involving more than 100 children younger than 5 years that reported the effectiveness, safety, or immunogenicity of rotavirus vaccines were included. A random-effects model was used to calculate relative risks (RRs), odds ratios (ORs), risk differences, and 95% CIs. Adjusted indirect treatment comparison was performed to assess the differences in the protection of Rotarix and RotaTeq. The primary outcomes were RVGE, severe RVGE, and RVGE hospitalization. Safety-associated outcomes involved serious adverse events, intussusception, and mortality. A meta-analysis of 20 RCTs and 38 case-control studies revealed that Rotarix (RV1) significantly reduced RVGE (RR, 0.316 [95% CI, 0.224-0.345]) and RVGE hospitalization risk (OR, 0.347 [95% CI, 0.279-0.432]) among children fully vaccinated; RotaTeq (RV5) had similar outcomes (RVGE: RR, 0.350 [95% CI, 0.275-0.445]; RVGE hospitalization risk: OR, 0.272 [95% CI, 0.197-0.376]). Rotavirus vaccines also demonstrated higher protection against severe RVGE. Additionally, no significant differences in the protection of RV1 and RV5 against rotavirus disease were noted in adjusted indirect comparisons. Moderate associations were found between reduced RVGE risk and Rotavac (RR, 0.664 [95% CI, 0.548-0.804]), Rotasiil (RR, 0.705 [95% CI, 0.605-0.821]), and Lanzhou lamb rotavirus vaccine (RR, 0.407 [95% CI, 0.332-0.499]). All rotavirus vaccines demonstrated no risk of serious adverse events. A positive correlation was also found between immunogenicity and vaccine protection (eg, association of RVGE with RV1: coefficient, -1.599; adjusted R2, 99.7%). The high protection and low risk of serious adverse events for rotavirus vaccines in children who were fully vaccinated emphasized the importance of worldwide introduction of rotavirus vaccination. Similar protection provided by Rotarix and RotaTeq relieves the pressure of vaccines selection for health care authorities.

A systematic review of the risk of oral rotavirus vaccine and intussusception

In 1999, since the Rotashield, the first generation of oral Rotavirus vaccine has been confirmed that there is a link to intussusception, mainly occurs in 7 days after first dose. With the second generation of RV vaccine has been listed globally and intussusception monitoring has continued. This study reviewed the current phase Ⅲ clinical and post-marketing studies of rotavirus vaccines on the market and found that the two most widely used rotavirus vaccines, RV1 and RV5, were found the risk of intussusception increased within 7 days of ORV. The Lanzhou lamb rotavirus vaccine (LLR), which manufactured by Lanzhou Institute of Biological Products Co, also lacks Epidemiological surveies. With the introduction of RV5 in 2018, the role of rotavirus vaccine in the prevention and efforts of severe rotavirus diarrhea is increasing. It is urgent to establish an intussusception active monitoring system to monitor the incidence of intussusception after rotavirus vaccine and provide more evidence for the post-marketing evaluation of the rotavirus vaccine.

Effectiveness of Lanzhou lamb rotavirus vaccine in preventing gastroenteritis among children younger than 5 years of age

BackgroundLanzhou Lamb rotavirus (LLR) vaccine was licensed in China in 2000. It was the only vaccine available in private market before 2018. However, the data about the post-marketing effectiveness is very limited. To assess the vaccine effectiveness (VE), we conducted a case-control study based on the hospital surveillance system in Beijing from 2015 to 2017. MethodsSeven hospitals located in seven districts in Beijing, from October 1, 2015, to March 31, 2017, were included. The VE of LLR vaccine was assessed in laboratory-confirmed rotavirus infection among children younger than five years old through a case-control design, using rotavirus-negative cases as controls. LLR vaccination was documented from a vaccination registry. VE was estimated adjusting for age group, gender, study site, the month of illness onset and interval days between illness onset to sampling through a logistic regression model. ResultsA total of 598 cases and 1766 controls were included in this study. The vaccine average coverage rate during 2015–2017 among children younger than five years old was 10.8% in Beijing. The adjusted VE for LLR vaccine of 1 dose versus 0 dose was 34.9% (95%CI, 5.3–55.3). We also obtained the adjusted VE of 87.7% (95%CI, 32.7–97.8) for patients with the severity score ≥11, 36.2% (95%CI, 4.7–57.3) for children of 2–35 months age group and 40.8% (95%CI, 7.8–61.9) against G9 rotavirus infection. Vaccinated cases were less likely to have watery stool (OR = 0.42) and have diarrhea longer than 5 days (OR = 0.47) than unvaccinated cases. DiscussionLLR vaccine conferred protection against rotavirus disease. Children who were vaccinated presented with less severe clinical manifestations. An immunization schedule of receiving all three doses in the first year should be preferred.

Rotavirus Gastroenteritis Infection Among Children Vaccinated and Unvaccinated With Rotavirus Vaccine in Southern China

Since 2000, the Lanzhou lamb rotavirus vaccine has been exclusively licensed in China for voluntary rotavirus gastroenteritis (RV-GE) prevention. To evaluate the association of the Lanzhou lamb rotavirus vaccination with RV-GE among children in southern China. This cross-sectional, ecological study was set in Guangzhou, China. Participants were infants possibly vaccinated (aged 2 months to 3 years) and the children ineligible for vaccination (aged ≥4 years). The study was conducted from May 1, 2007, to April 30, 2016, and the data analysis was conducted in July 2016. Annual median age at onset of RV-GE and seasonal distribution of incidence. Cases of RV-GE in Guangzhou, China, diagnosed from May 1, 2007, to April 30, 2016, and reported to the National Information System for Disease Control and Prevention were examined. Poisson regression models were fitted among 32 452 children younger than 4 years and among 450 children who had been ineligible for vaccination, while controlling for secular trends, socioeconomic status, and meteorological factors. Logistic regression was used to assess the indirect effects provided by the vaccinated infants from 2009 to 2011 on unvaccinated infants aged 2 to 35 months based on a separate case-control data set. During 9 seasons, 119 705 patients with gastroenteritis were reported; 33 407 were confirmed for RV-GE (21 202 [63.5%] male, 32 022 [95.8%] aged <4 years, and 31 306 [93.8%] residing in urban districts). The median age at onset for all patients with RV-GE increased from 11 months during the 2007 season to 15 months during the 2015 season, and the onset, peak, and cessation of incidence were delayed. When citywide vaccination coverage in the prior 12 months was classified into high and low groups (≥8.36% vs <8.36%), the incidence rate ratio for the high coverage group decreased by 32.4% among children younger than 4 years (incidence rate ratio, 0.676; 95% CI, 0.659-0.693; P < .001). Among the children ineligible for vaccination, the incidence rate ratio in higher coverage periods was 0.790 (95% CI, 0.351-0.915; P < .001) compared with the lower coverage. Compared with districts with 14% or less vaccination coverage, the adjusted odds ratio for RV-GE among unvaccinated children younger than 3 years was 0.85 (95% CI, 0.73-0.99; P = .03) for districts with 15% to 19% of coverage, and 0.79 (95% CI, 0.67-0.93; P = .004) for districts with more than 20% of coverage. This study provides evidence of the population health benefits of the Lanzhou lamb rotavirus vaccination in preventing RV-GE among children in China younger than 4 years, including herd effects.

Prevalence and clinical profile of rotavirus A infection among diarrhoeal children and phylogenetic analysis with vaccine strains in Chengdu, West China, 2009-2014.

Rotaviruses are the most common cause of severe diarrhoeal disease in young children. However, little is known about the epidemiological and clinical profile of rotavirus A (RVA) in diarrhoeal children or the efficacy of Lanzhou lamb rotavirus vaccine (LLR) in Chengdu, China. This study aimed to determine the prevalence and clinical profile of RVA in diarrhoeal children and provide gene analysis information for RVA vaccination programmes. A total of 1121 faecal samples were collected from outpatient children with diarrhoea between 2009 and 2014. RT-PCR was performed to detect RVA infection and other gastroenteritis viruses. VP4 and VP7 genes of 13 RVA strains were sequenced to compare their similarity with vaccine strains. The overall RVA infection rate was 17.48%. G1 (54.72%) and G3 (18.87%) were the predominant G genotypes; P[8] (72.36%) and P[4] (11.38%) were the main P genotypes. Sixteen genotypes were identified; G1P[8] (57.33%) and G9P[8] (12.00%) were the most prevalent. The proportion of coinfection with RVA and other gastroenteritis viruses was 18.88%. RVA was mostly detected in winter and in diarrhoeal children 1-2 years of age. The genotypes of Rotarix and RotaTeq vaccines were consistent with RVA strains prevalent in Sichuan and shared high identity. RVA was one of the major aetiological agents of diarrhoeal children in Chengdu. Genotype distribution differed within each year and the gene analysis implied low efficacy of LLR. Continuous epidemiological monitoring of RVA is essential for the national vaccination programme.

Faecal shedding of rotavirus vaccine in Chinese children after vaccination with Lanzhou lamb rotavirus vaccine

Lanzhou lamb rotavirus vaccine (LLR) is an oral live attenuated vaccine first licensed in China in 2000. To date, > 60 million doses of LLR have been distributed to children. However, very little is known about faecal shedding of LLR in children. Therefore, faecal samples (n = 1,184) were collected from 114 children for 15 days post-vaccination in September–November 2011/2012. Faecal shedding and viral loads were determined by an enzyme immunoassay kit (EIA) and real-time RT-PCR. The complete genome was sequenced and the vaccine strain was isolated by culture in MA104 cells. Approximately 14.0% (16/114) of children had rotavirus-positive samples by EIA for at least 1 day post-vaccination. Viral loads in EIA-positive samples ranged from < 1.0 × 103 to 1.9 × 108 copies/g. Faecal shedding occurred as early as post-vaccination day 2 and as late as post-vaccination day 13 and peaked on post-vaccination day 5–10. One LLR strain was isolated by culture in MA104 cells. Sequence analysis showed 99% identity with LLR prototype strain. Faecal shedding of LLR in stool is common within 15 days of LLR vaccination, indicating vaccine strains can replicate in human enteric tissues.

Porcine circovirus type 1 was undetected in vaccine but could be cultured in the cell substrate of Lanzhou lamb rotavirus vaccine.

In 2010, Rotarix was found to be contaminated with infectious porcine circovirus type 1 (PCV1). In China, the Lanzhou lamb rotavirus (LLR) vaccine is the only vaccine used to prevent rotavirus disease. From 2006 to September 2014, more than 54 million doses of LLR vaccines have been lot released. It is a safety issue whether PCV1 is present in the LLR vaccine. Although the cell substrate of LLR, bovine kidney (BK), is different from that of Rotarix, we have investigated the cell’s permissivity for PCV1 by both infectivity and full-length PCR analysis. We have assessed the LLR using a quantitative PCR (qPCR) assay. A total of 171 random batches of LLR final products over a period of 5 years were tested, and no PCV1 was detected (0/171). Infectivity studies showed that two strains of PCV1, the PCV1-prototype, which was derived from PK-15 cells, and the mutant, PCV1-GSK, which was isolated from Rotarix, were capable of replicating in BK cells over a wide m.o.i. ranging from 10 to 0.01. After culture for 6 days, copies of PCV1-prototype DNA were higher than those of PCV1-GSK on average. The genome of the virus was detected at 6 days post-infection. In summary, the LLR vaccine is free of PCV1. Nevertheless, because PCV1 can replicate in the BK cell substrate, manufacturers need to be vigilant in monitoring for this adventitious agent.

Cost-effectiveness analysis of rotavirus vaccination in China: Projected possibility of scale-up from the current domestic option.

BackgroundRotavirus infection causes considerable disease burden of acute gastroenteritis (AGE) hospitalization and death among children less than 5 years in China. Although two rotavirus vaccines (Rotarix and RotaTeq) have been licensed in more than 100 countries in the world, the Lanzhou Lamb rotavirus vaccine (LLR) is the only vaccine licensed in China. This study aims to forecast the potential impacts of the two international vaccines compared to domestic LLR.MethodsAn economic evaluation was performed using a Markov simulation model. We compared costs at the societal aspect and health impacts with and without a vaccination program by LLR, Rotarix or RotaTeq. Parameters including demographic, epidemiological data, costs and efficacy of vaccines were obtained from literature review. The model incorporated the impact of vaccination on reduction of incidence of rotavirus infection and severity of AGE indicated by hospitalization, inpatient visits and deaths. Outcomes are presented in terms of quality-adjusted life years (QALYs) gained and incremental cost-effectiveness ratio (ICER) compared to status quo.ResultsIn a hypothetical cohort of 100,000 infants, the two international vaccines showed very good cost-effectiveness, with ICER of Rotateq and Rotarix shifting from LLR of $1715.11/QALY and $2105.66/QALY, respectively. Rotateq and Rotarix had significantly decreased incidence compared to LLR, particularly among infants aged 6 months to 2 years.ConclusionsRotaTeq is expected to introduce in the national routine immunization program to reduce disease burden of rotavirus infection with universal coverage.

Vaccination status of Lanzhou lamb rotavirus vaccine in children aged 2 months to 5 years in Changning District, Shanghai

Vaccination status of Lanzhou lamb rotavirus vaccine in children aged 2 months to 5 years in Changning District, Shanghai

Evaluation of oral Lanzhou lamb rotavirus vaccine via passive transfusion with CD4+/CD8+ T lymphocytes

Lanzhou Lamb derived Rotavirus (RV) Vaccine (namely LLR) for children is only used in China. Since there were no reports on evaluation of LLR, even the data of phase IV clinical trial, we proceed the evaluation of LLR through focusing on T-cell to investigate whether LLR could induce the potential function involving in protection as a vaccine. Four groups of nude mice were transfused with CD4+/CD8+ T-cells isolated from LLR-immunized (primed) and LLR-unimmunized (naïve) mice via intraperitonea (i.p.) respectively. Consequently, the adoption mice were challenged with mice-origin wild rotavirus EDIM (Epizootic Diarrhea of Infant Mice) by intragastric administration. Series of fecal/serum samples were collected and viral shedding, then serum IgA/IgG and secreted IgA were assayed. Compared to the mice transfused with T lymphocytes from naïve mice, the nude mice transfused with CD4+ T lymphocytes from primed mice induce fecal and serum IgA increasing more rapidly, and have a shorter duration of virus shedding too. Whereas, no significant difference in virus clearance was found between the mice transfused with CD8+ T lymphocytes isolated from primed and naïve mice. Therefore, we cleared the distinct roles of transfused CD4+/CD8+ T lymphocytes for rotavirus clearance in nude mice, that the viral clearance conducted by CD4+ T lymphocytes. Meanwhile, it has ability to help induction of LLR specific immunogenicity. Comparing with the transfusion of cell from primed and naïve mice, LLR can induce CD4+ T lymphocytes memory which is a potential index to reflect the immunogenicity and protection, while CD8+ T lymphocytes remove rotavirus by CTL with little memory ability.

Effectiveness of the live attenuated rotavirus vaccine produced by a domestic manufacturer in China studied using a population-based case–control design

A universal rotavirus (RV) immunization program is a potentially cost-effective measure for preventing RV infection in China. However, the efficacy of the only licensed RV vaccine (Lanzhou lamb rotavirus vaccine, LLR), which is made by a domestic manufacturer, has not been proven by a properly designed clinical trial. In October 2011 to March 2012, to measure the potential protection provided by LLR, a case–control study nested in a population-based active diarrhea surveillance study of children <5 years of age was conducted in rural Zhengding county. During the study period, 308 episodes of diarrhea were identified as being caused by RV infection, resulting in an incidence rate of 48.0/1000 people/year. The predominant RV serotype was G3 (61.5%), followed by G1 (15.2%), and G9 (6.5%). Overall, a protection of 35.0% (95% confidence interval (CI), 13.0%–52.0%) was identified, and higher protection was found among moderate RV gastroenteritis cases caused by the serotype G3 (52.0%; 95% CI: 2.0%–76.1%). A concurrently conducted case–control study comparing non-RV viral diarrheal cases with non-diarrheal controls in the same population found that the RV vaccine offered no protection against non-RV diarrhea. Even under a less ideal immunization schedule, the oral LLR conferred a certain level of protection against RV gastroenteritis. However, further studies are needed to understand the full characteristics of the LLR, including its efficacy when administered following the optimal regimen, the potential risk of inducing intussusception, and the direct and indirect protective effects of LLR.

Active, population-based surveillance for rotavirus gastroenteritis in Chinese children: Beijing Municipality and Gansu Province, China.

Estimates of population-based incidence for rotavirus inpatient and outpatient visits, as well as their associated medical costs, can provide valuable information to assess the potential benefits of rotavirus vaccination. We conducted active surveillance for rotavirus gastroenteritis at 6 medical institutions for children younger than 5 years from July 2012 to June 2013 in Beijing Municipality and Gansu Province. We collected stool samples of diarrhea patients for testing rotavirus, and epidemiological, clinical and cost data. The proportion of rotavirus-positive for inpatient and outpatient visits from Beijing was 28.7% (138/481) and 19.4% (133/687); a statistically lower proportion than observed in Gansu among inpatient visits (45.2%, 245/542, P < 0.001) and among outpatient visits (28.8%, 66/229, P = 0.003), respectively. The G9P[8] genotype was most prevalent in Beijing (60.6%) and in Gansu (77.6%). The median Vesikari scale value was 16 for rotavirus inpatients and 15 for nonrotavirus inpatients. Population-based estimated rates of rotavirus-related hospitalizations were 14.4 (95% CI, 13-16) per 10,000 children, and the rate of rotavirus gastroenteritis in the outpatient setting was 149 (95% CI, 145-153) per 10,000 children younger than 5 years. The estimated total number of rotavirus-related inpatient visits were 3790 (95% CI, 2488-3827) cases and 29,101 (95% CI: 27,748-29,279) outpatient visits. The total cost of rotavirus infection was $1.4 million (95% CI, $0.9-1.4 million) for hospitalizations and $4.2 million (95% CI, $4.0-4.2 million) for outpatient visits per year in Beijing and Gansu. Rotavirus is the most common cause of severe acute gastroenteritis (AGE) in children younger than 5 years worldwide,accounting for an estimated 25 million clinic visits, 2 million hospitalizations and 453,000 deaths each year. In China, the world's most populous nation, surveillance at sentinel hospitals showed that approximately 48% of AGE hospitalizations among children younger than 5 years were attributed to rotavirus from 2003 to 2007, and 13,387 rotavirus deaths were estimated in China in 2002 alone.The Lanzhou lamb rotavirus vaccine, consisting of serotype G10P[12], was licensed in 2000 but is not included in the National Expanded Program of Immunization vaccine recommendations for Chinese children. License applications for new rotavirus vaccines (Rotarix, produced by GlaxoSmithKline Biologicals, and RotaTeq, produced by Merck and Company) have been submitted for administering these vaccines to Chinese infants [corrected].

113 Epidemics of Acute Gastroenteritis Caused by Viruses and Vaccine Development in China

The leading etiological agents of viral gastroenteritis are group A rotaviruses, noroviruses, adenoviruses (type 40, 41) and astroviruses in China in the last 20 years. The prevailing serotypes of rotaviruses are G type 1, 2, 3, 4 and 9, while G8 has been emerged recently in China. Accordingly, trivalent and hexavalent vaccines are under development by the two Institutes under CNBG. The trivalent oral vaccines are reassortants of VP4 and VP7 genes of human strains and other backbone genes of Lanzhou lamb rotavirus (LLR). The safety of lamb rotavirus vaccine strain has been proved since licensing in 2000 in China. The phase 3 clinical trials of the trivalent vaccines are in the progress in Henan province, China. The hexavalent oral vaccines are reassortants of VP7 genes of human strains and the other genes of UK strain, developed by and collaborated with NIH, USA, and PATH. The preclinical studies at Wuhan Institute of Biological Product have been completed and the hexavalent vaccine is ready for phase 1 clinical study. The novoviruses are increasingly detected in epidemics of acute viral gastroenteritis and spontaneous cases of people of all ages in China, including the rapid spreading of the newly emerged pandemic GII.4 variant (Sydney strain 2012) to China. The new Sydney strains were isolated in different areas and analysis of complete sequence demonstrated the rapid evolution. The surveillances and epidemic studies of these emerging viruses support the development of vaccines against the infections caused by noroviruses. The new variant co-circulated with other genotypes of GI and GII genogroups in human and multiple valent vaccines may needed to be developed.

Rotavirus Vaccination Coverage among Children Aged 2-59 Months: A Report from Guangzhou, China

ObjectiveWe aimed to estimate the Lanzhou lamb rotavirus (LLR) vaccination coverage (VC) and timeliness among children aged 2 to 59 months in Guangzhou, China.MethodsAn electronic system-based VC survey was conducted using stratified cluster random sampling.ResultsWe reported an overall Lanzhou lamb rotavirus vaccine coverage of 25.3% among children aged 2-59 months (2-8 months, 2.6%) in Guangzhou, China.ConclusionGreat efforts should be taken to increase LLR VC in eligible children in Guangzhou, China.

Effectiveness of the Lanzhou lamb rotavirus vaccine against gastroenteritis among children

The Lanzhou lamb rotavirus (LLR) vaccine has been in use in China since 2000. This study evaluated this vaccine's effectiveness using a case–control design in Guangzhou. In the study area, there were 3130 laboratory-confirmed rotavirus gastroenteritis cases in children between 2 and 35 months old from 2009 to 2011. A total of 3607 controls were also enrolled in this study. Of the subjects, 970 (14.4%) had received 1 dose of the LLR vaccine. Because of the low vaccination rate, we only obtained an effectiveness of 44.3% (95% CI, 28.4–56.7%) for children 9–11 months old, 52.8% (40.8–62.3%) for children 12–17 months old, and 51.8% (11.6–73.8%) for children 18–35 months old for one dose. This post-marketing study found that one dose of the LLR vaccine confers partial protection when given to children between 9 and 35 months old. Therefore, earlier immunization and the administration of the full immunization regimen should be encouraged.

Development of Neutralizing Monoclonal Antibodies Against VP4 of Rotavirus CC0812-1

The G10P[15] rotavirus CC0812-1 isolated from a diarrheal woman in Wuhan, China, in 2008 is phylogenetically close to the Lanzhou lamb rotavirus (LLR) of a monovalent human rotavirus vaccine produced by the Lanzhou Institute of Biological Products, China, and rotavirus Lamb-NT. This rotavirus can be used as the backbone of the attenuated rotavirus reassortant as a rotavirus vaccine candidate. In this study, rotavirus CC0812-1 was purified from the culture supernatant of CC0812-1-infected MA104 cells and used as antigen to immunize BALB/c mice. Four hybridoma clones were developed secreting antibodies that reacted with CC0812-1, designated as 1B1, 1B8, 1F11, and 1G10, respectively. Western blot analysis indicated that the four monoclonal antibodies (MAbs) were all specific for VP4 of rotavirus CC0812-1. Isotyping revealed that MAbs 1B1, 1B8, and 1G10 belonged to the IgM class, while MAb 1F11 belonged to the IgG1 subclass. A neutralization test demonstrated that the four MAbs all had the capacity to neutralize rotavirus CC0812-1. The neutralizing titers of the BALB/c mice ascites were 1:2048, 1:1024, 1:512, and 1:512 for MAbs 1B1, 1B8, 1F11, and 1G10, respectively.