Showing papers by "Hilary Koprowski published in 2007"

Failure To Open the Blood-Brain Barrier and Deliver Immune Effectors to Central Nervous System Tissues Leads to the Lethal Outcome of Silver-Haired Bat Rabies Virus Infection

Abstract: Rabies is a lethal disease caused by neurotropic viruses that are endemic in nature. When exposure to a potentially rabid animal is recognized, prompt administration of virus-neutralizing antibodies, together with active immunization, can prevent development of the disease. However, once the nonspecific clinical symptoms of rabies appear conventional postexposure treatment is unsuccessful. Over the last decade, rabies viruses associated with the silver-haired bat (SHBRV) have emerged as the leading cause of human deaths from rabies in the United States and Canada as a consequence of the fact that exposure to these viruses is often unnoticed. The need to treat SHBRV infection following the development of clinical rabies has lead us to investigate why the immune response to SHBRV fails to protect at a certain stage of infection. We have established that measurements of innate and adaptive immunity are indistinguishable between mice infected with the highly lethal SHBRV and mice infected with an attenuated laboratory rabies virus strain. While a fully functional immune response to SHBRV develops in the periphery of infected animals, the invasion of central nervous system (CNS) tissues by immune cells is reduced and, consequently, the virus is not cleared. Our data indicate that the specific deficit in the SHBRV-infected animal is an inability to enhance blood-brain barrier permeability in the cerebellum and deliver immune effectors to the CNS tissues. Conceivably, at the stage of infection where immune access to the infected CNS tissues is limited, either the provision or the development of antiviral immunity will be ineffective.

Smallpox subunit vaccine produced in planta confers protection in mice

Abstract: We report here the in planta production of the recombinant vaccinia virus B5 antigenic domain (pB5), an attractive component of a subunit vaccine against smallpox. The antigenic domain was expressed by using efficient transient and constitutive plant expression systems and tested by various immunization routes in two animal models. Whereas oral administration in mice or the minipig with collard-derived insoluble pB5 did not generate an anti-B5 immune response, intranasal administration of soluble pB5 led to a rise of B5-specific immunoglobulins, and parenteral immunization led to a strong anti-B5 immune response in both mice and the minipig. Mice immunized i.m. with pB5 generated an antibody response that reduced virus spread in vitro and conferred protection from challenge with a lethal dose of vaccinia virus. These results indicate the feasibility of producing safe and inexpensive subunit vaccines by using plant production systems.

Expression of influenza A (H5N1) vaccine in barley grains for oral bird immunization

Abstract: Outbreaks of the highly pathogenic avian influenza A (H5N1) virus killed thousands of wild and domestic birds in Asia. Single human fatalities caused by the H5N1 strain have also been reported recently. The H5N1 strain has spread further, and animals infected by the virus, probably through contact with migratory birds, have been found in Europe. The development of a cost-effective vaccine for the immunization of both domestic and wild birds is mandatory. Furthermore, control of H5N1 through vaccination in the avian population will greatly reduce the risk of virus transfer across species. It is of great interest that a major outbreak in humans, as was observed in 1918, will be avoided. Our strategy to generate a vaccine against the H5N1 influenza A virus is based on the expression of hemagglutinin (HA), a major virus surface antigen, in plant tissue that may be used for massive oral immunization of birds. Various transient and stable plant expression systems have been tested. Among those, a codon-optimized HA1 antigen driven by the seed specific a-gliadin promoter of wheat resulted in the highest expression. Representative molecular and biochemical analyses of transgenic barley have been performed. Western blot analysis revealed a particularly high expression of HA1 in the seeds of two out of 84 transgenic lines. Immunological evaluations of recombinant H5N1 hemagglutinin antigen are in progress.

Cruciferae-based plant system for the generation and production of recombinant proteins and vaccines

Abstract: The present invention relates to a method for the generation of transgenic Brassica oleracea plants, in particular transgenic Cruciferae (also known as Brassicaceae) plants. The present invention also provides a method for the production of heterologous proteins using a Cruciferae-based plant system, for example pharmaceutical and/or recombinant proteins. In particular the invention also relates to a method for the production of transgenic collard and cauliflower, and to the large scale production of pharmaceutical and/or therapeutic production, such as production of Cruciferae-based vaccine production.

Methods and uses of cauliflower and collard for recombinant protein production

Abstract: The present invention relates to a method for the generation of transgenic Brassica oleracea plants, in particular transgenic Cruciferae (also known as Brassicaceae) plants. The present invention also provides a method for the production of heterologous proteins using a Cruciferae-based plant system, for example pharmaceutical and/or recombinant proteins. In particular the invention also relates to a method for the production of transgenic collard and cauliflower, and to the large scale production of pharmaceutical and/or therapeutic production, such as production of Cruciferae-based vaccine production.