Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults

Fix, Alan; Harro, Clayton; McNeal, Monica; Dally, Len; Flores, Jorge; Robertson, George A.; Boslego, John W.; Cryz, Stanley

doi:10.1016/j.vaccine.2015.05.024

Cited by 54 publications

(68 citation statements)

References 31 publications

(44 reference statements)

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“…The P2-VP8-P [8] protein was produced at the Walter Reed Army Institute of Research, Pilot Bioproduction Facility (Silver Spring, MD, USA). 17 The protein was diluted using sterile saline and formulated with aluminium hydroxide (Alhydrogel, Brenntag Biosector, Frederikssund, Denmark) by the study pharmacist within 6 h of administration to yield dose concentrations of See Online for appendix 10 µg, 30 µg, and 60 µg per 0·5 mL containing 0·56 mg of aluminium. An injection of sterile saline was used as placebo.…”

Section: Methodsmentioning

confidence: 99%

Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial

Groome

Koen

Fix

et al. 2017

The Lancet Infectious Diseases

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115

118

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Section: Methodsmentioning

confidence: 99%

Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial

Groome

Koen

Fix

et al. 2017

The Lancet Infectious Diseases

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115

118

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“…52 A candidate P2-VP8 subunit vaccine has been shown to be well-tolerated in human Phase 1 clinical studies. 53 It is hoped that these candidates will improve efficacy against severe rotavirus gastroenteritis and be associated with lower manufacturing costs. 47 While parenteral vaccine candidates are under clinical development, the mucosal route has additional potential benefits in the context of rotavirus immunization.…”

Section: Development Of New Rotavirus Vaccine Candidatesmentioning

confidence: 99%

Options for improving effectiveness of rotavirus vaccines in developing countries

Tissera

Cowley

Bogdanovic-Sakran

et al. 2017

Human Vaccines & Immunotherapeutics

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Rotavirus gastroenteritis is a leading global cause of mortality and morbidity in young children due to diarrhea and dehydration. Over 85% of deaths occur in developing countries. In industrialised countries, 2 live oral rotavirus vaccines licensed in 2006 quickly demonstrated high effectiveness, dramatically reducing severe rotavirus gastroenteritis admissions in many settings by more than 90%. In contrast, the same vaccines reduced severe rotavirus gastroenteritis by only 30-60% in developing countries, but have been proven life-saving. Bridging this "efficacy gap" offers the possibility to save many more lives of children under the age of 5. The reduced efficacy of rotavirus vaccines in developing settings may be related to differences in transmission dynamics, as well as host luminal, mucosal and immune factors. This review will examine strategies currently under study to target the issue of reduced efficacy and effectiveness of oral rotavirus vaccines in developing settings.

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“…In a phase 1 clinical trial conducted in infants and toddlers in South Africa, a monovalent NRRV vaccine containing aluminum-adjuvanted P [8] antigen was shown to be well-tolerated and immunogenic, thus demonstrating a promising approach to develop a new vaccine against RV. 16,17 Moreover, a trivalent version of the aluminum-adjuvanted NRRV vaccine is currently being evaluated in infants and toddlers in early stage clinical trials in South Africa. 16 The trivalent NRRV vaccine candidate is composed of 3 recombinant protein antigens designed to protect against the most prevalent RV strains in the developing world (P [4], P [6], and P [8]).…”

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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Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults

Abstract: NCT01764256.

Cited by 54 publications

References 31 publications

Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial

Safety and immunogenicity of a parenteral P2-VP8-P[8] subunit rotavirus vaccine in toddlers and infants in South Africa: a randomised, double-blind, placebo-controlled trial

Options for improving effectiveness of rotavirus vaccines in developing countries

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

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