scholarly journals Oral rotavirus vaccine shedding as a marker of mucosal immunity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Lee ◽  
Md Abdul Kader ◽  
E. Ross Colgate ◽  
Marya Carmolli ◽  
Dorothy M. Dickson ◽  
...  
Keyword(s):  
Mucosal Immunity ◽  
Human Infection ◽  
Rotavirus Vaccine ◽  
Oral Vaccines ◽  
Post Dose ◽  
Virus Shedding ◽  
Immune Correlates ◽  
Infection Models ◽  
Group A Rotaviruses ◽  
Group A

AbstractGroup A rotaviruses (RVA) remain a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries. Improved immune correlates of protection (CoP) for existing oral vaccines and novel strategies to evaluate the performance of next-generation vaccines are needed. Use of oral vaccines as challenge agents in controlled human infection models is a potential approach to CoP discovery that remains underexplored. In a live-attenuated, oral rotavirus vaccine (Rotarix, GlaxoSmithKline) efficacy trial conducted among infants in Dhaka, Bangladesh, we explored the potential for the second dose of the two-dose series to be considered a challenge agent through which RVA immunity could be explored, using fecal virus shedding post-dose 2 as a marker of mucosal immunity. Among 180 vaccinated infants who completed the parent study per protocol, the absence of fecal vaccine shedding following the second dose of Rotarix suggested intestinal mucosal immunity generated by the first dose and a decreased risk of RVA diarrhea through 2 years of life (RR 0.616, 95% CI 0.392–0.968). Further development of controlled human infection models for group A rotaviruses, especially in prospective studies with larger sample sizes, may be a promising tool to assess rotavirus vaccine efficacy and CoPs.

scholarly journals Oral Rotavirus Vaccine Shedding as a Marker of Mucosal Immunity

2021 ◽  
Author(s):  
Benjamin Lee ◽  
Abdul Kader ◽  
E. Ross Colgate ◽  
Marya Carmolli ◽  
Dorothy M. Dickson ◽  
...  
Keyword(s):  
Mucosal Immunity ◽  
Human Infection ◽  
Rotavirus Vaccine ◽  
Oral Vaccines ◽  
Post Dose ◽  
Middle Income ◽  
Virus Shedding ◽  
Immune Correlates ◽  
Promising Tool ◽  
Infection Models

Abstract Rotavirus remains a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries (LMIC). Improved immune correlates of protection (CoP) for existing oral vaccines and novel strategies to evaluate the performance of next-generation vaccines are needed. Use of oral vaccines as challenge agents in controlled human infection models is a potential approach to CoP discovery that remains underexplored. In a live-attenuated, oral rotavirus vaccine (Rotarix, GlaxoSmithKline) efficacy trial conducted among infants in Dhaka, Bangladesh, we explored the potential for the second dose of the two-dose series to be considered a challenge agent through which rotavirus immunity could be explored, using fecal virus shedding post-dose 2 as a marker of mucosal immunity. Among 180 vaccinated infants who completed the parent study per protocol, the absence of fecal vaccine shedding following the second dose of Rotarix suggested intestinal mucosal immunity generated by the first dose and a decreased risk of rotavirus diarrhea through 2 years of life (RR 0.616, 95% CI 0.392-0.968). Further development of controlled human infection models for rotavirus, especially in prospective studies with larger sample sizes, may be a promising tool to assess rotavirus vaccine efficacy and CoPs.

Molecular characterization of the first human G15 rotavirus strain of zoonotic origin from the bovine species

2021 ◽  
Vol 102 (4) ◽  
Author(s):  
Takeshi Tsugawa ◽  
Yoshiki Fujii ◽  
Yusuke Akane ◽  
Saho Honjo ◽  
Kenji Kondo ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Molecular Characterization ◽  
Human Infection ◽  
Potential Reservoir ◽  
Group A Rotaviruses ◽  
Paediatric Outpatient ◽  
Group A ◽  
Human Infections ◽  
Bovine Species

Group A rotaviruses (RVAs) infect a wide variety of mammalian and avian species. Animals act as a potential reservoir to RVA human infections by direct virion transmission or by contributing genes to reassortants. Here, we report the molecular characterization of a rare human RVA strain Ni17-46 with a genotype G15P[14], isolated in Japan in 2017 during rotavirus surveillance in a paediatric outpatient clinic. The genome constellation of this strain was G15-P[14]-I2-R2-C2-M2-A13-N2-T9-E2-H3. This is the first report of an RVA with G15 genotype in humans, and sequencing and phylogenetic analysis results suggest that human infection with this strain has zoonotic origin from the bovine species. Given the fact that this strain was isolated from a patient with gastroenteritis and dehydration symptoms, we must take into account the virulence of this strain in humans.

scholarly journals ComparativeIn VitroandIn VivoStudies of Porcine Rotavirus G9P[13] and Human Rotavirus Wa G1P[8]

2015 ◽  
Vol 90 (1) ◽  
pp. 142-151 ◽  
Author(s):  
Lulu Shao ◽  
David D. Fischer ◽  
Sukumar Kandasamy ◽  
Abdul Rauf ◽  
Stephanie N. Langel ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Cells ◽  
Experimental Studies ◽  
Cross Protection ◽  
Short Term ◽  
Susceptible Host ◽  
Virus Shedding ◽  
Vaccine Candidates ◽  
Group A Rotaviruses ◽  
Group A

ABSTRACTThe changing epidemiology of group A rotavirus (RV) strains in humans and swine, including emerging G9 strains, poses new challenges to current vaccines. In this study, we comparatively assessed the pathogenesis of porcine RV (PRV) G9P[13] and evaluated the short-term cross-protection between this strain and human RV (HRV) Wa G1P[8] in gnotobiotic pigs. Complete genome sequencing demonstrated that PRV G9P[13] possessed a human-like G9 VP7 genotype but shared higher overall nucleotide identity with historic PRV strains. PRV G9P[13] induced longer rectal virus shedding and RV RNAemia in pigs than HRV Wa G1P[8] and generated complete short-term cross-protection in pigs challenged with HRV or PRV, whereas HRV Wa G1P[8] induced only partial protection against PRV challenge. Moreover, PRV G9P[13] replicated more extensively in porcine monocyte-derived dendritic cells (MoDCs) than did HRV Wa G1P[8]. Cross-protection was likely not dependent on serum virus-neutralizing (VN) antibodies, as the heterologous VN antibody titers in the sera of G9P[13]-inoculated pigs were low. Thus, our results suggest that heterologous protection by the current monovalent G1P[8] HRV vaccine against emerging G9 strains should be evaluated in clinical and experimental studies to prevent further dissemination of G9 strains. Differences in the pathogenesis of these two strains may be partially attributable to their variable abilities to replicate and persist in porcine immune cells, including dendritic cells (DCs). Additional studies are needed to evaluate the emerging G9 strains as potential vaccine candidates and to test the susceptibility of various immune cells to infection by G9 and other common HRV/PRV genotypes.IMPORTANCEThe changing epidemiology of porcine and human group A rotaviruses (RVs), including emerging G9 strains, may compromise the efficacy of current vaccines. An understanding of the pathogenesis and genetic, immunological, and biological features of the new emerging RV strains will contribute to the development of new surveillance and prevention tools. Additionally, studies of cross-protection between the newly identified emerging G9 porcine RV strains and a human G1 RV vaccine strain in a susceptible host (swine) will allow evaluation of G9 strains as potential novel vaccine candidates to be included in porcine or human vaccines.

scholarly journals Molecular Epidemiology of Rotavirus Strains in Symptomatic and Asymptomatic Children in Manhiça District, Southern Mozambique 2008–2019

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 134
Author(s):  
Filomena Manjate ◽  
Eva D. João ◽  
Percina Chirinda ◽  
Marcelino Garrine ◽  
Delfino Vubil ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Molecular Epidemiology ◽  
Rotavirus Vaccine ◽  
Severe Diarrhoea ◽  
Chain Reaction ◽  
Vaccine Introduction ◽  
Asymptomatic Children ◽  
Group A Rotaviruses ◽  
Group A ◽  
Polymerase Chain

Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix®) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction.

Molecular Epidemiological Traits of Group A Rotaviruses in Japanese Children During Transitional Period of Rotavirus Vaccine Implementation, 2011 - 2014

2017 ◽  
Vol 63 (05+06/2017) ◽  
Author(s):  
Sayaka Takanashi ◽  
Aksara Thongprachum ◽  
Shoko Okitsu ◽  
Shuichi Nishimura ◽  
Masaaki Kobayashi ◽  
...  
Keyword(s):  
Transitional Period ◽  
Rotavirus Vaccine ◽  
Japanese Children ◽  
Group A Rotaviruses ◽  
Group A

scholarly journals Rotaviruses and Rotavirus Vaccines

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 959
Author(s):  
Celeste M. Donato ◽  
Julie E. Bines
Keyword(s):  
Capsid Proteins ◽  
Virus Family ◽  
Rotavirus Vaccines ◽  
Group A Rotaviruses ◽  
Group A ◽  
Outer Capsid

Group A rotaviruses belong to the Reoviridae virus family and are classified into G and P genotypes based on the outer capsid proteins VP7 and VP4, respectively [...]

scholarly journals The Rotavirus Vaccine Landscape, an Update

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 520
Author(s):  
Roberto Cárcamo-Calvo ◽  
Carlos Muñoz ◽  
Javier Buesa ◽  
Jesús Rodríguez-Díaz ◽  
Roberto Gozalbo-Rovira
Keyword(s):  
Developing Countries ◽  
Mortality Rate ◽  
Low Income ◽  
State Of The Art ◽  
The State ◽  
Cold Chain ◽  
Low Income Countries ◽  
Rotavirus Vaccine ◽  
Oral Vaccines

Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.

scholarly journals A Survey of G6 and G10 Serotypes of Group a Bovine Rotaviruses from Diarrheic Beef and Dairy Calves using Monoclonal Antibodies in ELISA

1994 ◽  
Vol 6 (2) ◽  
pp. 175-181 ◽  
Author(s):  
A. Lucchelli ◽  
S. Y. Kang ◽  
M. K. Jayasekera ◽  
A. V. Parwani ◽  
D. H. Zeman ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
South Dakota ◽  
Dairy Herd ◽  
Dairy Calves ◽  
Enzyme Linked Immunosorbent Assay ◽  
Positive Stool ◽  
Field Samples ◽  
Group A Rotaviruses ◽  
Beef Herds ◽  
Group A

Group A bovine rotaviruses (BRV) have been identified worldwide as a major cause of diarrhea in the young of many species, including humans. Group A rotaviruses are classified into serotypes on the basis of the outer capsid proteins, VP7 (G types) and VP4 (P types). To date, there are 14 G types of group A rotaviruses, with G1, G6, G8, and G10 described for BRV isolates. In this study, G6- and G lo-specific monoclonal antibodies (MAbs) were used in an enzyme-linked immunosorbent assay (ELISA) for the G typing of BRV-positive stool samples from diarrheic beef and dairy calves from South Dakota, Ohio, Michigan, Nebraska, and Washington, USA, and Ontario, Canada. ELISA plates were coated using a broadly reactive VP7 MAb (Common 60) or with G6- or G10-specific MAbs. BRV-positive fecal samples were diluted and added to duplicate wells, followed by the addition of polyclonal guinea pig anti-group A rotavirus serum as the secondary antibody. Several reference G6 and G10 BRV strains as well as other G types previously reported in cattle (G1, G2, G3, G8) and BRV-negative samples were included as G type specificity and negative controls. From a total of 308 field samples analyzed, 79% (244/308) tested positive by the broadly reactive VP7 MAb; of these, 54% (131/244) were G6 positive, 14% (35/244) were G10 positive, 4% (9/244) were both G6 and G10 positive, and 28% (69/244) were G6 and G10 negative. The negative samples may represent additional or undefined serotypes. The 89 samples from South Dakota were further subdivided into samples from beef ( n = 43) or dairy ( n = 46) herds. G6 was more prevalent in beef herd samples (67%) than in dairy herd samples (47.5%). In addition, dairy herds had higher percentages of G10-positive samples (17.5%) G6-G10 double positives (10%), and untypable samples (25%) than did beef herds, in which the prevalence of G10 positive samples was 5.5%, G6-G10 double positives was 5.5%, and untypable samples was 22%. Application of the serotype ELISA for the analysis of additional BRV samples will provide further epidemiologic data on the distribution of BRV serotypes in beef or dairy cattle, an important consideration for the development of improved BRV vaccines.

scholarly journals Progress and challenges in TB vaccine development

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 199 ◽  
Author(s):  
Gerald Voss ◽  
Danilo Casimiro ◽  
Olivier Neyrolles ◽  
Ann Williams ◽  
Stefan H.E. Kaufmann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Scientific Progress ◽  
Human Infection ◽  
Experimental Medicine ◽  
Vaccine Platform ◽  
Vaccine Candidates ◽  
Clinical Endpoints ◽  
Immune Correlates ◽  
Efficacy Trials

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

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