Mattheolabakis G.,University of Patras |
Lagoumintzis G.,University of Patras |
Panagi Z.,University of Patras |
Papadimitriou E.,University of Patras |
And 2 more authors.
International Journal of Pharmaceutics | Year: 2010
We investigated the influence of antigen entrapment in PLA nanoparticles on the immune responses obtained after transcutaneous immunization. OVA-loaded PLA nanoparticles were prepared using a double emulsion process. Following application onto bare skin of mice in vivo, fluorescence-labeled nanoparticles were detected in the duct of the hair follicles indicating that the nanoparticles can penetrate the skin barrier through the hair follicles. Although the OVA-loaded nanoparticles elicited lower antibody responses than those induced by OVA in aqueous solution they were more efficient in inducing cytokine responses. In vitro re-stimulation of cultured splenocytes with OVA elicited a little higher levels of IFN-γ (difference statistically insignificant, p > 0.05) and significantly higher levels of IL-2 (p < 0.001) in mice immunized with OVA-loaded nanoparticles compared to those immunized with OVA in solution. In the presence of CT, the OVA-loaded nanoparticles induced significantly higher IFN-γ and IL-2 than all other formulations. Transcutaneous administration of OVA encapsulated in the PLA nanoparticles exhibited priming efficacy to a challenging dose of OVA given via different route. These findings indicate the potential of nanoparticles to deliver antigens via the transcutaneous route and prime for antibody and strong cellular responses. The co-administration of an adjuvant such as CT had the added advantage of modulating the immune response, a desirable characteristic within the context of vaccination against intracellular versus extracellular pathogens. © 2009 Elsevier B.V. All rights reserved.
Osorio J.E.,Inviragen |
Huang C.Y.-H.,University of Wisconsin - Madison |
Kinney R.M.,University of Wisconsin - Madison |
Stinchcomb D.T.,Inviragen |
Stinchcomb D.T.,Centers for Disease Control and Prevention
Vaccine | Year: 2011
Dengue. virus infection is the leading arboviral cause of disease worldwide. A vaccine is being developed based on the attenuated DEN-2 virus, DEN-2 PDK-53. In this review, we summarize the characteristics of the parent DEN-2 PDK-53 strain as well as the chimeric viruses containing the prM and E genes of DEN-1, DEN-3 or DEN-4 virus in the genetic backbone of the DEN-2 PDK-53 virus (termed DENVax). Tetravalent DENVax formulations containing cloned, fully sequenced isolates of the DEN-2 PDK-53 virus and the three chimeras have been evaluated for safety and efficacy in preclinical animal models. Based on the safety, immunogenicity and efficacy in preclinical studies, Phase 1 clinical testing of DENVax has been initiated. © 2011 Elsevier Ltd.
Weaver S.C.,University of Texas Medical Branch |
Osorio J.E.,Inviragen |
Livengood J.A.,Inviragen |
Chen R.,University of Texas Medical Branch |
Expert Review of Vaccines | Year: 2012
In 2004, chikungunya virus (CHIKV) re-emerged from East Africa to cause devastating epidemics of debilitating and often chronic arthralgia that have affected millions of people in the Indian Ocean Basin and Asia. More limited epidemics initiated by travelers subsequently occurred in Italy and France, as well as human cases exported to most regions of the world, including the Americas where CHIKV could become endemic. Because CHIKV circulates during epidemics in an urban mosquito-human cycle, control of transmission relies on mosquito abatement, which is rarely effective. Furthermore, there is no antiviral treatment for CHIKV infection and no licensed vaccine to prevent disease. Here, we discuss the challenges to the development of a safe, effective and affordable chikungunya vaccine and recent progress toward this goal. © 2012 Expert Reviews Ltd.
Caine E.A.,University of Wisconsin - Madison |
Partidos C.D.,Inviragen |
Santangelo J.D.,Inviragen |
Osorio J.E.,University of Wisconsin - Madison |
PLoS ONE | Year: 2013
Non-polio enteroviruses, including enterovirus 71 (EV71), have caused severe and fatal cases of hand, foot and mouth disease (HFMD) in the Asia-Pacific region. The development of a vaccine or antiviral against these pathogens has been hampered by the lack of a reliable small animal model. In this study, a mouse adapted EV71 strain was produced by conducting serial passages through A129 (α/β interferon (IFN) receptor deficient) and AG129 (α/β, γ IFN receptor deficient) mice. A B2 sub genotype of EV71 was inoculated intraperitoneally (i.p.) into neonatal AG129 mice and brain-harvested virus was subsequently passaged through 12 and 15 day-old A129 mice. When tested in 10 week-old AG129 mice, this adapted strain produced 100% lethality with clinical signs including limb paralysis, eye irritation, loss of balance, and death. This virus caused only 17% mortality in same age A129 mice, confirming that in the absence of a functional IFN response, adult AG129 mice are susceptible to infection by adapted EV71 isolates. Subsequent studies in adult AG129 and young A129 mice with the adapted EV71 virus examined the efficacy of an inactivated EV71 candidate vaccine and determined the role of humoral immunity in protection. Passive transfer of rabbit immune sera raised against the EV71 vaccine provided protection in a dose dependent manner in 15 day-old A129 mice. Intramuscular injections (i.m.) in five week-old AG129 mice with the alum adjuvanted vaccine also provided protection against the mouse adapted homologous strain. No clinical signs of disease or mortality were observed in vaccinated animals, which received a prime-and-boost, whereas 71% of control animals were euthanized after exhibiting systemic clinical signs (P<0.05). The development of this animal model will facilitate studies on EV71 pathogenesis, antiviral testing, the evaluation of immunogenicity and efficacy of vaccine candidates, and has the potential to establish correlates of protection studies. © 2013 Caine et al.
Inviragen | Date: 2014-03-13
Embodiments herein relate to compositions of and methods for live attenuated alphaviruses. In certain embodiments, a live, attenuated virus composition includes, but is not limited to, one or more live, attenuated alphaviruses and compositions to reduce inactivation and/or degradation of the live, attenuated alphavirus. In other embodiments, the live, attenuated virus composition may be a vaccine composition. In yet other compositions, a live, attenuated alphavirus composition may include HEPES buffer. In other embodiments, the HEPES buffer may further include a carbohydrate and gelatin and/or a salt.
Inviragen | Date: 2010-11-24
Embodiments of the present invention generally disclose methods, compositions and uses for generating and expressing enterobacterial-associated peptides. In some embodiments, enterobacterial-associated peptides include, but are not limited to plague-associated peptides. In certain embodiments, methods generally relate to making and using compositions of constructs including, but not limited to, attenuated or modified vaccinia virus vectors expressing enterobacterial-associated peptides. In other embodiments, vaccine compositions are reported of use in a subject.
The Government Of The United States Of America As Represented By The Secretary Of Health & Human S and Inviragen | Date: 2013-11-08
Embodiments herein report compositions, methods and uses for dengue-4 (DENV-4) virus constructs. Some embodiments concern a composition that includes, but is not limited to, DENV-4 virus constructs alone or in combination with other constructs, can be used in a vaccine composition to induce an immune response in a subject. In certain embodiments, compositions can include constructs of more than one serotypes of dengue virus, such as dengue-1 virus, dengue-2 virus, or dengue-3 virus in combination with DENV-4 virus constructs disclosed herein. In other embodiments, DENV-4 constructs disclosed herein can be combined in a composition with other flavivirus constructs to generate a vaccine against more than one flavivirus. Other embodiments provide methods and uses for DENV-4 virus constructs in vaccine compositions that when administered to a subject induce an immune response in the subject against DENV-4 that is improved by modified constructs compared to other vaccine compositions.
The Government Of The United States Of America As Represented By The Secretar and Inviragen | Date: 2014-03-13
Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.
News Article | June 2, 2015
DEERFIELD, Ill. & OSAKA, Japan--(BUSINESS WIRE)--Takeda Pharmaceutical Company Limited (“Takeda”) will consolidate its Vaccine Business Unit (VBU) operations by establishing global and regional hubs as the organization continues to grow and advance its important vaccine programs in norovirus, dengue and seasonal influenza. The Boston/Cambridge, Massachusetts area, and Zurich, Switzerland will serve as VBU’s global hubs for the vaccine business outside of Japan. VBU will maintain regional hubs in Singapore and in Brazil and will operate manufacturing sites in Hikari, Japan; Durham, North Carolina and Singen, Germany. In the U.S., all vaccine activities with the exception of manufacturing will move to the new global hub in the Boston/Cambridge area. This co-location will significantly enhance communication and collaboration across VBU’s divisions, and will allow VBU to leverage Takeda’s significant R&D presence in Cambridge. It will also provide access to the area’s remarkable biotech/pharmaceutical ecosystem and talent base. Takeda will close its vaccine site in Bozeman, Montana, which it obtained through the acquisition of Ligocyte Pharmaceuticals in 2012, as well as the Madison, Wisconsin and Fort Collins, Colorado sites, which came to Takeda through the acquisition of Inviragen, Inc. in 2013. In addition, vaccine activities in Deerfield, Illinois, which currently serves as the global headquarters for VBU, will shift to the Boston/Cambridge area. This transition will occur in phases over the next two years, with the completion of U.S. consolidation by mid-2017. “Takeda remains fully committed to the development of innovative vaccines that improve the lives of people around the world, including our norovirus, dengue and seasonal influenza candidate vaccines,” said Rajeev Venkayya, M.D., President, Takeda’s Vaccine Business Unit. “Our sites in Bozeman, Fort Collins, Madison and Deerfield have been instrumental in bringing our dengue and norovirus programs to late stages of clinical development. This consolidation will help us to achieve the efficiency and operational excellence needed to execute the Phase 3 clinical programs and set the stage for global commercialization of these vaccines.” Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for people worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com. Takeda has supplied vaccines to protect the health of people in Japan for more than 60 years. Currently headquartered in Deerfield, Illinois, Takeda’s global Vaccine Business was launched in January 2012. Today, development efforts are focused on tackling some of the world’s most challenging health problems for which vaccines do not exist, such as dengue and norovirus.