Recombinant Virus-like Particle Protein Vaccines

Sitrin, Robert D.; Zhao, Qinjian; Potter, Clinton S.; Carragher, Bridget; Washabaugh, Michael W.

doi:10.1007/978-3-662-45024-6_3

Cited by 7 publications

(4 citation statements)

References 56 publications

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“…Historically, animal-based immunogenicity tests have been used to assess the potency and stability of aluminum-adsorbed, inactivated/recombinant-based vaccines. 38,39 There is great interest in replacing these in vivo assays with surrogate in vitro assays to monitor antigenicity and stability of vaccines. ELISA is a commonly used in vitro immunochemical method to measure the concentration, antigenicity, or conformational integrity of protein antigens, depending on the nature of the antibody used (e.g., neutralizing vs. nonneutralizing, linear vs. conformational epitopes, and so forth).…”

Section: Analytical Challenges To Evaluate Nrrv Antigen Stability Boumentioning

confidence: 99%

Effect of Aluminum Adjuvant and Preservatives on Structural Integrity and Physicochemical Stability Profiles of Three Recombinant Subunit Rotavirus Vaccine Antigens

Hickey

McAdams

White

et al. 2020

Journal of Pharmaceutical Sciences

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A nonreplicating rotavirus vaccine (NRRV) containing 3 recombinant fusion proteins adsorbed to aluminum adjuvant (Alhydrogel [AH]) is currently in clinical trials. The compatibility and stability of monovalent NRRV antigen with key components of a multidose vaccine formulation were examined using physicochemical and immunochemical methods. The extent and strength of antigen-adjuvant binding were diminished by increasing phosphate concentration, and acceptable levels were identified along with alternate buffering agents. Addition of the preservative thimerosal destabilized AH-adsorbed P2-VP8-P[8] as measured by differential scanning calorimetry. Over 3 months at 4 C, AH-adsorbed P2-VP8-P[8] was stable, whereas at 25 C and 37 C, instability was observed which was greatly accelerated by thimerosal addition. Loss of antibody binding (enzyme-linked immunosorbent assay) correlated with loss of structural integrity (differential scanning calorimetry, fluorescence spectroscopy) with concomitant nonnative disulfide bond formation (sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and Asn deamidation (liquid chromatography-mass spectrometry peptide mapping). An alternative preservative (2phenoxyethanol) showed similar antigen destabilization. Due to limited availability, only key assays were performed with monovalent P2-VP8-P[4] and P2-VP8-P[6] AH-adsorbed antigens, and varying levels of preservative incompatibility were observed. In summary, monovalent AH-adsorbed NRRV antigens stored at 4 C showed good stability without preservatives; however, future formulation development efforts are required to prepare a stable, preservative-containing, multidose NRRV formulation.

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Section: Analytical Challenges To Evaluate Nrrv Antigen Stability Boumentioning

confidence: 99%

Effect of Aluminum Adjuvant and Preservatives on Structural Integrity and Physicochemical Stability Profiles of Three Recombinant Subunit Rotavirus Vaccine Antigens

Hickey

McAdams

White

et al. 2020

Journal of Pharmaceutical Sciences

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“…Using a multiple epitope approach for analysis of recombinant vaccine antigens leads to a more comprehensive evaluation of the epitope integrity. 41 Among the mAbs used for detecting the HEV antigen, 8C11 and 8G12 were two protective and neutralizing antibodies. MAb 8C11 recognized conformational epitopes that were composed of three discontinuous peptide segments in a dimeric form of the truncated HEV capsid protein.…”

Section: Discussionmentioning

confidence: 99%

Effect of freezing on recombinant hepatitis E vaccine

Dong

Gao

et al. 2019

Human Vaccines & Immunotherapeutics

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Studies have revealed that vaccines are more often exposed to sub-zero temperatures during cold chain transportation than what was previously known. Such exposure might be detrimental to the potency of temperature-sensitive vaccines. The aim of this study was to evaluate the impact of exposure to freezing on the physicochemical properties and biological activities of recombinant hepatitis E (rHE) vaccine. Changes in rHE vaccine due to freezing temperatures were analyzed with regard to sedimentation rate, antigenicity, and antibody affinity and potency. The freezing temperature of rHE was measured, then rHE vaccine was exposed to freezing temperatures below −10°C. Significant increase of sedimentation rate was noted, according to shake test and massed precipitates. In addition, the binding affinity of rHE vaccine to six specific monoclonal antibodies was significantly reduced and the in vivo potency for eliciting a protective IgG response was also partially lost, especially for anti-HEV neutralizing antibodies. Altogether, our work indicates that exposure of rHE vaccine to a temperature below −10°C results in the loss of structural integrity and biological potency of rHE vaccine.

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“…[30][31][32][33] Therefore, a one-site binding and label-free assay (i.e., surface plasmon resonance or SPR) [34][35][36] and a 2-site binding assay (i.e., a sandwich ELISA) 30,31,33 were carried out to evaluate the antibody binding activity of the HEV 239 antigen.…”

Section: Immunochemical Methodsmentioning

confidence: 99%

The development of a recombinant hepatitis E vaccine HEV 239

Zhao

et al. 2015

Human Vaccines & Immunotherapeutics

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108

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Hepatitis E virus (HEV) infection is one of the main causes of acute hepatitis worldwide. A recombinant hepatitis E vaccine, HEV 239, has been licensed in China for immunizing adults of 16 y old and above. The vaccine antigen contains pORF2 aa 368 -606 of the HEV genotype 1 expressed in E. coli. The quality of the vaccine is controlled through a combination of biophysical, biochemical and immunochemical methods. The vaccine is well tolerated in adults. The efficacy of the HEV 239 vaccine against symptomatic and asymptomatic infection had been proven to be high during a Phase III clinical trial and long-term follow up. The safety and efficacy of HEV 239 vaccine in certain high-risk populations remains to be further investigated.

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Recombinant Virus-like Particle Protein Vaccines

Cited by 7 publications

References 56 publications

Effect of Aluminum Adjuvant and Preservatives on Structural Integrity and Physicochemical Stability Profiles of Three Recombinant Subunit Rotavirus Vaccine Antigens

Effect of Aluminum Adjuvant and Preservatives on Structural Integrity and Physicochemical Stability Profiles of Three Recombinant Subunit Rotavirus Vaccine Antigens

Effect of freezing on recombinant hepatitis E vaccine

The development of a recombinant hepatitis E vaccine HEV 239

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