Next generation vaccines and vectors: Designing downstream processes for recombinant protein-based virus-like particles

2015 ◽  
Vol 10 (5) ◽  
pp. 715-727 ◽  
Author(s):  
Christopher Ladd Effio ◽  
Jürgen Hubbuch
Keyword(s):  
Recombinant Protein ◽  
Next Generation ◽  
Virus Like Particles ◽  
Downstream Processes

scholarly journals HPV-Impfstoffe – zugelassene Vakzinen und experimenteller RG1-VLP-Impfstoff der nächsten Generation

hautnah ◽  
2021 ◽  
Author(s):  
Christina Schellenbacher ◽  
Bettina Huber ◽  
Saeed Shafti-Keramat ◽  
Reinhard Kirnbauer
Keyword(s):  
High Risk ◽  
Phase I ◽  
Low Risk ◽  
Next Generation ◽  
Virus Like Particles

ZusammenfassungInfektionen mit >12 sexuell übertragbaren genitalen „high-risk“ (hr) humanen Papillomviren (HPV) sind hauptverantwortlich für anogenitale Karzinome, insbesondere Zervix- und Analkarzinome sowie oropharyngeale Karzinome, insgesamt für 5 % der Karzinome weltweit. Genitale „low-risk“ (lr) HPV und kutane HPV verursachen Anogenitalwarzen (Kondylome) bzw. Hautwarzen, kutane Genus β‑HPV sind ein potenzieller Kofaktor für die Entwicklung nichtmelanozytärer Hautkarzinome in Immunsupprimierten. Die zugelassenen HPV-Vakzinen sind Spaltimpfstoffe bestehend aus leeren Hauptkapsidproteinhüllen (L1-virus-like particles, VLP). Die prophylaktische Impfung mit dem modernen nonavalenten Impfstoff Gardasil‑9 (HPV6/11/16/18/31/33/45/52/58) verhindert persistierende Infektionen mit Typen, die bis zu 90 % der Zervixkarzinome und Kondylome verursachen. Der Impfschutz ist vorwiegend typenspezifisch, daher besteht kein Schutz gegen Infektionen mit den übrigen genitalen hrHPV oder Hauttypen. RG1-VLP ist ein experimenteller „next generation“-Impfstoff, bestehend aus HPV16L1-VLP, welche ein Kreuzneutralisierungs-Epitop des HPV16 Nebenkapsidproteins L2 („RG1“; Aminosäuren 17–36) repetitiv (360×) an der Oberfläche tragen. Eine Vakzinierung mit RG1-VLP schützt im Tierversuch gegen experimentelle Infektionen mit allen relevanten genitalen hrHPV (~96 % aller Zervixkarzinome), lrHPV (~90 % der Kondylome) sowie gegen einige kutane und β‑HPV. Präklinische Daten zeigen langanhaltende Protektion ohne Boosterimmunisierung ein Jahr nach der Impfung sowie Wirksamkeit nach nur 2 Dosen. Auch in lyophilisierter, thermostabiler Form bleibt die Immunogenität der RG1-VLP erhalten. Eine Phase-I-Studie ist mit Unterstützung des US NCI/NIH in Vorbereitung. Der vorliegende Artikel diskutiert Fragestellungen zur HPV-Impfstoffoptimierung und präsentiert den pan-HPV-Impfstoffkandidat RG1-VLP.

scholarly journals Mammalian expression of virus-like particles as a proof of principle for next generation polio vaccines

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Mohammad W. Bahar ◽  
Claudine Porta ◽  
Helen Fox ◽  
Andrew J. Macadam ◽  
Elizabeth E. Fry ◽  
...  
Keyword(s):  
Significant Risk ◽  
Next Generation ◽  
Wild Type ◽  
Inactivated Polio Vaccine ◽  
Vaccination Programs ◽  
Virus Like Particles ◽  
Mammalian Expression ◽  
Cryo Electron Microscopy ◽  
Alternative Expression ◽  
Antibody Titres

AbstractGlobal vaccination programs using live-attenuated oral and inactivated polio vaccine (OPV and IPV) have almost eradicated poliovirus (PV) but these vaccines or their production pose significant risk in a polio-free world. Recombinant PV virus-like particles (VLPs), lacking the viral genome, represent safe next-generation vaccines, however their production requires optimisation. Here we present an efficient mammalian expression strategy producing good yields of wild-type PV VLPs for all three serotypes and a thermostabilised variant for PV3. Whilst the wild-type VLPs were predominantly in the non-native C-antigenic form, the thermostabilised PV3 VLPs adopted the native D-antigenic conformation eliciting neutralising antibody titres equivalent to the current IPV and were indistinguishable from natural empty particles by cryo-electron microscopy with a similar stabilising lipidic pocket-factor in the VP1 β-barrel. This factor may not be available in alternative expression systems, which may require synthetic pocket-binding factors. VLPs equivalent to these mammalian expressed thermostabilized particles, represent safer non-infectious vaccine candidates for the post-eradication era.

scholarly journals VIRUS-LIKE-PARTICLES FOR NEXT GENERATION MICRO/NANO-BIOSENSORS

2014 ◽  
Author(s):  
X.Z. Fan ◽  
L. Naves ◽  
N.P. Siwak ◽  
A. Brown ◽  
J. Culver ◽  
...  
Keyword(s):  
Next Generation ◽  
Virus Like Particles

Addressing Next Generation Packaging and IoT with Glass Solutions

2016 ◽  
Vol 2016 (1) ◽  
pp. 000277-000281 ◽  
Author(s):  
Aric Shorey ◽  
Rachel Lu ◽  
Kevin Adriance ◽  
Gene Smith
Keyword(s):  
Mobile Communications ◽  
Mechanical Performance ◽  
Coefficient Of Thermal Expansion ◽  
Cost Effective ◽  
Next Generation ◽  
Glass Forming ◽  
Cost Structures ◽  
Downstream Processes ◽  
The Internet Of Things ◽  
Made In

Abstract New requirements are emerging in electronics packaging. The ever-growing need for solutions for mobile communications and sensors that address the Internet of Things (IoT) brings about interesting new challenges. RF applications strive to move to higher frequency bands, fan-out technology is being leveraged as an effective way to address interconnect demands, and there is a continuous search for more cost-effective solutions for difficult packaging challenges. Glass provides numerous opportunities to address these needs. As an insulator, glass has low electrical loss, particularly at high frequencies. The relatively high stiffness and ability to adjust coefficient of thermal expansion helps optimize warp in glass core substrates, and manage bonded stacks leveraging TGV and carrier applications. Glass forming processes allow to form in a panel format as well as wafer format at thicknesses as low as 100 μm, giving opportunities to optimize or eliminate current polishing type manufacturing methods and address packaging challenges in a cost effective way. As the industry adopts glass solutions, significant advancements have been made in downstream processes such as glass handling and via/surface metallization. Of particular interest is the ability to leverage tool sets and processes for panel fabrication to enable cost structures desired by the industry. We will provide the latest demonstrations of electrical, thermal and mechanical performance and reliability as well as describe areas where glass is being leveraged to achieve goals of next generation products.

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