Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic

Wen, Xiaobo; Cao, Dianjun; Jones, Ronald W.; Hoshino, Yasutaka; Yuan, Lijuan

doi:10.1080/21645515.2015.1054583

Cited by 19 publications

(13 citation statements)

References 45 publications

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“…The most advanced of the non-replicating candidates is a recombinant subunit parenteral rotavirus vaccine, developed as a truncated recombinant VP8 ∗ protein of human rotavirus genotypes P[8], P[4] or P[6] expressed in Escherichia coli at the US NIH [80], [81]. The vaccine constructs have been demonstrated to elicit serum neutralizing immune responses in animals, and the immunogenicity could be significantly enhanced when the constructs were fused with the P2 epitope of tetanus toxoid, which elicits a strong T-cell helper function [81]. PATH, Seattle has developed the vaccine construct further, including process optimization and adsorption of the P2-VP8 ∗ with aluminum hydroxide; clinical trial lots were produced at Walter Reed Army Institute for Research (WRAIR) for the human studies.…”

Section: Non-replicating Parenterally Delivered Rotavirus Vaccinesmentioning

confidence: 99%

The rotavirus vaccine development pipeline

Kirkwood

Carey

et al. 2019

Vaccine

108

162

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Rotavirus disease is a leading global cause of mortality and morbidity in children under 5years of age. The effectiveness of the two globally used oral rotavirus vaccines quickly became apparent when introduced into both developed and developing countries, with significant reductions in rotavirus-associated mortality and hospitalizations. However, the effectiveness and impact of the vaccines is reduced in developing country settings, where the burden and mortality is highest. New rotavirus vaccines, including live oral rotavirus candidates and non-replicating approaches continue to be developed, with the major aim to improve the global supply of rotavirus vaccines and for local implementation, and to improve vaccine effectiveness in developing settings. This review provides an overview of the new rotavirus vaccines in development by developing country manufacturers and provides a rationale why newer candidates continue to be explored. It describes the new live oral rotavirus vaccine candidates as well as the non-replicating rotavirus vaccines that are furthest along in development.

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Section: Non-replicating Parenterally Delivered Rotavirus Vaccinesmentioning

confidence: 99%

The rotavirus vaccine development pipeline

Kirkwood

Carey

et al. 2019

Vaccine

108

162

View full text Add to dashboard Cite

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“…9,10,12 Alternative approaches such as nonreplicating rotavirus vaccine (NRRV) candidates administered via the parenteral route may provide higher efficacy compared with oral rotavirus vaccination in these settings by eliminating the complications of the gastrointestinal route. 13,14 Parenteral vaccines may be manufactured at lower cost and could be delivered along with routine Expanded Program on Immunization vaccines via established networks, further reducing costs. 15 Rotavirus virions are double-stranded RNA particles classified by six nonstructural proteins (NSP1-NSP6) and six structural proteins (VP1-VP4, VP6 and VP7) which form a three-layered structure of inner core, inner capsid, and outer capsid.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Formulation and preclinical studies with a trivalent rotavirus P2-VP8 subunit vaccine

Lakatos¹,

McAdams²,

White³

et al. 2020

Human Vaccines & Immunotherapeutics

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More effective rotavirus vaccines are essential for preventing extensive diarrheal morbidity and mortality in children under five years of age in low-resource regions. Nonreplicating rotavirus vaccines (NRRV) administered parenterally provide an alternate vaccination method to the current licensed oral vaccine. Live attenuated vaccines and may generate increased efficacy in low-resource settings because the parenteral administration route bypasses some of the challenges associated with oral administration, including differences in intestinal environments. Work described here supports development of a trivalent NRRV vaccine for parenteral administration to avoid complications of the gastrointestinal route. Recombinant VP8* subunit proteins representing some of the most prevalent strains of rotavirus infecting humans-DS-1 (P[4]), 1076 (P[6]), and Wa (P[8])were combined with an aluminum adjuvant and the P2 epitope of tetanus toxoid to enhance the immune response to this NRRV antigen. Vaccine formulation development included selection of aluminum hydroxide (Alhydrogel®) as an appropriate adjuvant as well as an optimal buffer to maintain antigen stability and optimize antigen binding to the adjuvant. Characterization assays were used to select the lead vaccine formulation and monitor formulation stability. The NRRV liquid formulation was stable for one year at 2°C to 8°C and four weeks at 37°C. Immunogenicity of the NRRV formulation was evaluated using a guinea pig model, where we demonstrated that the adjuvant provided a 20-fold increase in neutralization titer against a homologous antigen and that the P2-fusion also enhanced the serum neutralizing antibody responses. This vaccine candidate is currently being evaluated in human clinical trials.

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“…Addressing this question through studies that withhold breastfeeding would require longer withholding periods that may not be feasible or ethical. To avoid interference of oral RV by breast milk, one potential option may be a shift to parenteral RV in LMIC (70)(71)(72)(73)(74)(75).…”

Section: Clinical Trials Of Rotavirus Vaccine Efficacy In Breastfed Amentioning

confidence: 99%

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

Mwila

Chilengi

Simuyandi

et al. 2017

Clin Vaccine Immunol

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The role of maternal immunity, received by infants either transplacentally or orally from breast milk, in rotavirus vaccine (RV) performance is evaluated here. Breastfeeding withholding has no effect on vaccine responses, but higher levels of transplacental rotavirus-specific IgG antibody contribute to reduced vaccine seroconversion. The gaps in knowledge on the factors associated with low RV efficacy in low-and middle-income countries (LMIC) remain, and further research is needed to shed more light on these issues. KEYWORDS immunization, low-and middle-income countries, maternal, rotavirus D espite the progress seen with the global introduction of rotavirus vaccines (RV), diarrhea is still a leading cause of death in children under the age of 5 years, and a substantial proportion of disease cases are still attributable to rotavirus infection. The latest estimates show that approximately 215,000 children die each year from rotavirusassociated diarrhea, and approximately 56% of these deaths are in sub-Saharan Africa (1). The World Health Organization (WHO) recommended the introduction of oral RV into national immunization programs (2), and many countries have heeded this call. As of September 2016, the WHO lists 86 countries as having included RV in their national immunization programs, and 6 more are in the course of doing so in 2016 (www.who.int/immunization/monitoring_surveillance/VaccineIntroStatus.pptx). Approximately 50% of the countries in Africa and Asia, over 80% of those in North America, South America, and Australia, and approximately 40% of those in Europe have introduced RV. Following RV introduction, there was a notable reduction in the number of deaths due to diarrhea (1). However, there is consistent evidence from clinical trials that RV have lower efficacies in low-and middle-income countries (LMIC): vaccine efficacies are 80 to 90% in high-income countries (HIC) and 40 to 60% in LMIC (3-8). Indeed, there is growing evidence from vaccine effectiveness studies emerging from the field that in real-life use, vaccine effectiveness is also consistently lower in LMIC (9-12).In addition to the differences in observed vaccine efficacy and effectiveness, there are also marked differences in vaccine-elicited immunity as reported by various vaccine-elicited antibody titers following rotavirus immunization (13)(14)(15)(16)(17)(18). A number of hypotheses have been put forward to explain the differences in efficacy and vaccineelicited immunity between HIC and LMIC. The hypotheses include (i) maternal factors (such as interference from transplacental antibodies and antibody and nonantibody breast milk components [13,[19][20][21][22][23] [38,39]). A better understanding of these factors which decrease the efficacy of RV in LMIC may help to inform interventions to improve efficacy and to further reduce the number of child deaths due to rotavirus disease. This review examines the correlations between maternal immune factors and RV responses and their potential effect on vaccine efficacy. NATURAL ROTAVIRUS...

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Tandem truncated rotavirus VP8* subunit protein with T cell epitope as non-replicating parenteral vaccine is highly immunogenic

Cited by 19 publications

References 45 publications

The rotavirus vaccine development pipeline

The rotavirus vaccine development pipeline

Formulation and preclinical studies with a trivalent rotavirus P2-VP8 subunit vaccine

Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries

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