A Phase 1 Dose Escalation Study to Assess the Safety and Immunogenicity of a Monovalent Virus-Like Particle (VLP) Venezuelan Equine Encephalitis Vaccine in Healthy Adults

The primary objective of the study is to evaluate the safety and immunogenicity of non-adjuvanted and adjuvanted monovalent VEE VLP Vaccine in healthy adults (ages 18-50 years) when administered via intramuscular (IM) injection at escalating doses of 2 μg, 10 μg, and 20 μg as a 2-dose primary series (Day 0, Day 28) with a Day 140 booster dose. The secondary objective of the study is to evaluate immunogenicity of the vaccine at the aforementioned time points

开始日期2018-07-17

申办/合作机构

SRI International

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100 项与 Monovalent venezuelan equine encephalitis (VEE) virus-like particle vaccine (SRI International) 相关的临床结果

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100 项与 Monovalent venezuelan equine encephalitis (VEE) virus-like particle vaccine (SRI International) 相关的转化医学

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100 项与 Monovalent venezuelan equine encephalitis (VEE) virus-like particle vaccine (SRI International) 相关的专利（医药）

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项与 Monovalent venezuelan equine encephalitis (VEE) virus-like particle vaccine (SRI International) 相关的文献（医药）

2018-06-01·Journal of Virology2区 · 医学

Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform

2区 · 医学

Article

作者: Menachery, Vineet D. ; Whitmore, Alan ; Lindesmith, Lisa C. ; Scobey, Trevor ; Schäfer, Alexandra ; Baric, Ralph S. ; Agnihothram, Sudhakar ; Yount, Boyd L. ; Heise, Mark T.

ABSTRACT Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and in vivo efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens. IMPORTANCE While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.

2016-02-01·Vaccine3区 · 医学

Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates

3区 · 医学

Article

作者: Pickens, Jennifer A ; Johnston, Robert E ; Schultz-Darken, Nancy ; Smith-House, Frances ; Johnson, Monika ; Tollefson, Sharon J ; Bates, John T ; Crowe, James E ; Slaughter, James C ; Schuster, Jennifer E ; Williams, John V ; Davis, Nancy L

Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV) are major causes of illness among children, the elderly, and the immunocompromised. No vaccine has been licensed for protection against either of these viruses. We tested the ability of two Venezuelan equine encephalitis virus-based viral replicon particle (VEE-VRP) vaccines that express the hRSV or hMPV fusion (F) protein to confer protection against hRSV or hMPV in African green monkeys. Animals immunized with VEE-VRP vaccines developed RSV or MPV F-specific antibodies and serum neutralizing activity. Compared to control animals, immunized animals were better able to control viral load in the respiratory mucosa following challenge and had lower levels of viral genome in nasopharyngeal and bronchoalveolar lavage fluids. The high level of immunogenicity and protective efficacy induced by these vaccine candidates in nonhuman primates suggest that they hold promise for further development.

2013-05-15·Journal of Virology2区 · 医学

Venezuelan Equine Encephalitis Replicon Particles Can Induce Rapid Protection against Foot-and-Mouth Disease Virus

2区 · 医学

Article

作者: Weiss, Marcelo ; Perez-Martin, Eva ; Moraes, Mauro P. ; Custer, Max ; Owens, Gary ; Grubman, Marvin J. ; Diaz-San Segundo, Fayna ; de los Santos, Teresa ; Dias, Camila C. A. ; Kamrud, Kurt

ABSTRACTWe have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replicationin vitroandin vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 107or 108infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV.

100 项与 Monovalent venezuelan equine encephalitis (VEE) virus-like particle vaccine (SRI International) 相关的药物交易

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