Current status of rotavirus vaccines

Wang, Ching-Min; Chen, Shou-Chien; Chen, Kow-Tong

doi:10.1007/s12519-015-0038-y

Cited by 22 publications

(20 citation statements)

References 82 publications

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“…2 Improvements in sanitation, personal hygiene, or food quality reduce but do not eliminate the risk of this infection. 3,4 Therefore, vaccination is the most cost-effective strategy to control the burden of RV-related illness.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Subunit Rotavirus Trivalent Vaccine Candidate: Physicochemical Comparisons and Stability Evaluations of Three Protein Antigens

Hickey

Sahni

Toth

et al. 2020

Journal of Pharmaceutical Sciences

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a b s t r a c tAlthough live attenuated Rotavirus (RV) vaccines are available globally to provide protection against enteric RV disease, efficacy is substantially lower in low-to middle-income settings leading to interest in alternative vaccines. One promising candidate is a trivalent nonreplicating RV vaccine, comprising 3 truncated RV VP8 subunit proteins fused to the P2 CD4 þ epitope from tetanus toxin (P2-VP8-P[4/6/8]). A wide variety of analytical techniques were used to compare the physicochemical properties of these 3 recombinant fusion proteins. Various environmental stresses were used to evaluate antigen stability and elucidate degradation pathways. P2-VP8-P[4] and P2-VP8-P[6] displayed similar physical stability profiles as function of pH and temperature while P2-VP8-P[8] was relatively more stable. Forced degradation studies revealed similar chemical stability profiles with Met 1 most susceptible to oxidation, the single Cys residue (at position 173/172) forming intermolecular disulfide bonds (P2-VP8-P[6] was most susceptible), and Asn 7 undergoing the highest levels of deamidation. These results are visualized in a structural model of the nonreplicating RV antigens. The establishment of key structural attributes of each antigen, along with corresponding stability-indicating methods, have been applied to vaccine formulation development efforts (see companion paper), and will be utilized in future analytical comparability assessments.

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Section: Introductionmentioning

confidence: 99%

Recombinant Subunit Rotavirus Trivalent Vaccine Candidate: Physicochemical Comparisons and Stability Evaluations of Three Protein Antigens

Hickey

Sahni

Toth

et al. 2020

Journal of Pharmaceutical Sciences

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“…Even though two oral vaccines containing attenuated live viruses are being used globally, Rotarix (GlaxoSmithKline) and RotaTeq (Merck), the epidemic in the developing world is far from being controlled (6, 7). Vaccine effectiveness is reduced in developing areas, and some possible reasons are children infected at an early age, high viral challenge loads, and the lack of transferred maternal antibodies (8, 9). …”

Section: Introductionmentioning

confidence: 99%

Intestinal Innate Antiviral Immunity and Immunobiotics: Beneficial Effects against Rotavirus Infection

2016

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The mucosal tissues of the gastrointestinal tract are the main portal entry of pathogens such as rotavirus (RV), which is a leading cause of death due to diarrhea among young children across the globe and a major cause of severe acute intestinal infection in livestock animals. The interactions between intestinal epithelial cells (IECs) and immune cells with RVs have been studied for several years, and now, it is known that the innate immune responses triggered by this virus can have both beneficial and detrimental effects for the host. It was demonstrated that natural RV infection in infants and experimental challenges in mice result in the intestinal activation of pattern recognition receptors (PRRs) such as toll-like receptor 3 (TLR3) and striking secretion of proinflammatory mediators that can lead to increased local tissue damage and immunopathology. Therefore, modulating desregulated intestinal immune responses triggered by PRRs activation are a significant promise for reducing the burden of RV diseases. The ability of immunoregulatory probiotic microorganisms (immunobiotics) to protect against intestinal infections, such as those caused by RVs, is among the oldest effects studied for these important group of beneficial microbes. In this review, we provide an update of the current status on the modulation of intestinal antiviral innate immunity by immunobiotics and their beneficial impact on RV infection. In addition, we describe the research of our group that demonstrated the capacity of immunobiotic strains to beneficially modulated TLR3-triggered immune response in IECs, reduce the disruption of intestinal homeostasis caused by intraepithelial lymphocytes, and improve the resistance to RV infections.

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“…Limited information on therapeutic targets have impeded efforts for RV-specific drug discovery and development (Bagchi et al, 2012). Thus, vaccination remains the primary prophylactic strategy to reduce the disease burden of RV (Glass et al, 2006;Wang et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Integrated molecular and bioprocess engineering for bacterially produced immunogenic modular virus‐like particle vaccine displaying 18 kDa rotavirus antigen

Tekewe

Fan

Tan

et al. 2016

Biotech & Bioengineering

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A high global burden of rotavirus disease and the unresolved challenges with the marketed rotavirus vaccines, particularly in the developing world, have ignited efforts to develop virus-like particle (VLP) vaccines for rotavirus. While rotavirus-like particles comprising multiple viral proteins can be difficult to process, modular VLPs presenting rotavirus antigenic modules are promising alternatives in reducing process complexity and cost. In this study, integrated molecular and bioprocess engineering approaches were used to simplify the production of modular murine polyomavirus capsomeres and VLPs presenting a rotavirus 18 kDa VP8* antigen. A single construct was generated for dual expression of non-tagged murine polyomavirus capsid protein VP1 and modular VP1 inserted with VP8*, for co-expression in Escherichia coli. Co-expressed proteins assembled into pentameric capsomeres in E. coli. A selective salting-out precipitation and a polishing size exclusion chromatography step allowed the recovery of stable modular capsomeres from cell lysates at high purity, and modular capsomeres were successfully translated into modular VLPs when assembled in vitro. Immunogenicity study in mice showed that modular capsomeres and VLPs induced high levels of VP8*-specific antibodies. Our results demonstrate that a multipronged synthetic biology approach combining molecular and bioprocess engineering enabled simple and low-cost production of highly immunogenic modular capsomeres and VLPs presenting conformational VP8* antigenic modules. This strategy potentially provides a cost-effective production route for modular capsomere and VLP vaccines against rotavirus, highly suitable to manufacturing economics for the developing world. Biotechnol. Bioeng. 2017;114: 397-406. © 2016 Wiley Periodicals, Inc.

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Current status of rotavirus vaccines

Abstract: Rotavirus is a common cause of diarrhea in children in both developed and developing countries. Rotavirus vaccination is a cost-effective measure to prevent rotavirus diarrhea.

Cited by 22 publications

References 82 publications

Recombinant Subunit Rotavirus Trivalent Vaccine Candidate: Physicochemical Comparisons and Stability Evaluations of Three Protein Antigens

Recombinant Subunit Rotavirus Trivalent Vaccine Candidate: Physicochemical Comparisons and Stability Evaluations of Three Protein Antigens

Intestinal Innate Antiviral Immunity and Immunobiotics: Beneficial Effects against Rotavirus Infection

Integrated molecular and bioprocess engineering for bacterially produced immunogenic modular virus‐like particle vaccine displaying 18 kDa rotavirus antigen

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