Matching Items (6)
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Description
Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector

Vaccinia virus (VACV) is the current vaccine for the highly infectious smallpox disease. Since the eradication of smallpox, VACV has been developed extensively as a heterologous vaccine vector for several pathogens. However, due to the complications associated with this replication competent virus, the safety and efficacy of VACV vaccine vector has been reevaluated. To evaluate the safety and efficacy of VACV, we study the interactions between VACV and the host innate immune system, especially the type I interferon (IFN) signaling pathways. In this work, we evaluated the role of protein kinase R (PKR) and Adenosine Deaminase Acting on RNA 1(ADAR1), which are induced by IFN, in VACV infection. We found that PKR is necessary but is not sufficient to activate interferon regulatory factor 3 (IRF3) in the induction of type I IFN; and the activation of the stress-activated protein kinase/ c-Jun NH2-terminal kinase is required for the PKR-dependent activation of IRF3 during VACV infection. Even though PKR was found to have an antiviral effect in VACV, ADAR1 was found to have a pro-viral effect by destabilizing double stranded RNA (dsRNA), rescuing VACVΔE3L, VACV deleted of the virulence factor E3L, when provided in trans. With the lessons we learned from VACV and host cells interaction, we have developed and evaluated a safe replication-competent VACV vaccine vector for HIV. Our preliminary results indicate that our VACV vaccine vector can still induce the IFN pathway while maintaining the ability to replicate and to express the HIV antigen efficiently. This suggests that this VACV vector can be used as a safe and efficient vaccine vector for HIV.
ContributorsHuynh, Trung Phuoc (Author) / Jacobs, Bertram L (Thesis advisor) / Hogue, Brenda (Committee member) / Chang, Yung (Committee member) / Ugarova, Tatiana (Committee member) / Arizona State University (Publisher)
Created2013
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Description

Pearl Luella Kendrick researched prevention for pertussis, commonly known as whooping cough, in Grand Rapids, Michigan, during the mid-1900s. Pertussis is a respiratory disease that mainly affects infants and young children. During the 1920s, pertussis was responsible for more deaths in children in the United States than any other disease.

Pearl Luella Kendrick researched prevention for pertussis, commonly known as whooping cough, in Grand Rapids, Michigan, during the mid-1900s. Pertussis is a respiratory disease that mainly affects infants and young children. During the 1920s, pertussis was responsible for more deaths in children in the United States than any other disease. In the 1930s, Kendrick created one of the first pertussis vaccines that underwent large-scale clinical trials. Towards the end of her career, Kendrick helped developed combination vaccines for other common childhood diseases at the time, including diphtheria, tetanus, pertussis, and poliomyelitis. She also studied immune responses in infants whose mothers had pertussis antibodies that transferred to them during pregnancy. Kendrick helped lower the incidence and death rate of pertussis and other common childhood diseases in the US through the creation of vaccines.

Created2022-12-23
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Description

The measles, mumps, and rubella (MMR) vaccine was created by Maurice Hilleman in 1971 at the Merck Institute of Therapeutic Research, a pharmaceutical company in West Point, Pennsylvania. It combined three separate vaccines for measles, mumps, and rubella, common and sometimes fatal diseases. Measles causes a red skin rash and

The measles, mumps, and rubella (MMR) vaccine was created by Maurice Hilleman in 1971 at the Merck Institute of Therapeutic Research, a pharmaceutical company in West Point, Pennsylvania. It combined three separate vaccines for measles, mumps, and rubella, common and sometimes fatal diseases. Measles causes a red skin rash and severe fevers that can be fatal. Mumps causes fever and swelling of the salivary glands in the mouth and jaw, while rubella causes milder fevers and skin rashes. Pregnant women that contract rubella sometimes pass the virus to their fetuses, causing congenital rubella syndrome, which results in malformations of the eyes, ears, heart, and brain in the fetuses. The MMR vaccine has protected millions of people from contracting the potentially deadly diseases of measles, mumps, and rubella, as well as prevented the development congenital rubella syndrome in the fetuses.

Created2017-03-30
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Maurice Ralph Hilleman developed vaccines at the Merck Institute of Therapeutic Research in West Point, Pennsylvania, during the twentieth century. Over the course of his career at Merck, Hilleman created over forty vaccines, making him one of the most prolific developers of vaccine in the twentieth century. Of the fourteen

Maurice Ralph Hilleman developed vaccines at the Merck Institute of Therapeutic Research in West Point, Pennsylvania, during the twentieth century. Over the course of his career at Merck, Hilleman created over forty vaccines, making him one of the most prolific developers of vaccine in the twentieth century. Of the fourteen vaccines commonly given to children in the US by 2015, Hilleman was responsible for eight of them. Hilleman's most widely used vaccine was his measles, mumps, and rubella (MMR) vaccine. Hilleman's MMR vaccine prevented many diseases and also rubella in millions of children and pregnant women. Rubella in pregnant women often led to congenital rubella syndrome in the fetus, causing severe malformations.

Created2017-04-13
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Description

Stanley Alan Plotkin developed vaccines in the United States during the mid to late twentieth century. Plotkin began his research career at the Wistar Institute in Philadelphia, Pennsylvania, where he studied the rubella virus. In pregnant women, the rubella virus caused congenital rubella syndrome in the fetus, which led to

Stanley Alan Plotkin developed vaccines in the United States during the mid to late twentieth century. Plotkin began his research career at the Wistar Institute in Philadelphia, Pennsylvania, where he studied the rubella virus. In pregnant women, the rubella virus caused congenital rubella syndrome in the fetus, which led to various malformations and birth defects. Using WI-38 cells, a line of cells that originated from tissues of aborted fetuses, Plotkin successfully created RA27/3, a weakened strain of the rubella virus, which he then used to develop a rubella vaccine. Plotkin’s rubella vaccine has prevented birth defects due to congenital rubella in developing fetuses and newborns.

Created2017-04-13
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Description
The HIV-1 pandemic continues to cause millions of new infections and AIDS-related deaths each year, and a majority of these occur in regions of the world with limited access to antiretroviral therapy. Therefore, an HIV-1 vaccine is still desperately needed. The most successful HIV-1 clinical trial to date used a

The HIV-1 pandemic continues to cause millions of new infections and AIDS-related deaths each year, and a majority of these occur in regions of the world with limited access to antiretroviral therapy. Therefore, an HIV-1 vaccine is still desperately needed. The most successful HIV-1 clinical trial to date used a non-replicating canarypox viral vector and protein boosting, yet its modest efficacy left room for improvement. Efforts to derive novel vectors which can be both safe and immunogenic, have spawned a new era of live, viral vectors. One such vaccinia virus vector, NYVAC-KC, was specifically designed to replicate in humans and had several immune modulators deleted to improve immunogenicity and reduce pathogenicity. Two NYVAC-KC vectors were generated: one expressing the Gag capsid, and one with deconstructed-gp41 (dgp41), which contains an important neutralizing antibody target, the membrane proximal external region (MPER). These vectors were combined with HIV-1 Gag/dgp41 virus-like particles (VLPs) produced in the tobacco-relative Nicotiana benthamiana. Different plant expression vectors were compared in an effort to improve yield. A Geminivirus-based vector was shown to increase the amount of MPER present in VLPs, thus potentially enhancing immunogenicity. Furthermore, these VLPs were shown to interact with the innate immune system through Toll-like receptor (TLR) signaling, which activated antigen presenting cells to induce a Th2-biased response in a TLR-dependent manner. Furthermore, expression of Gag and dgp41 in NYVAC-KC vectors resulted in activation of antiviral signaling pathways reliant on TBK1/IRF3, which necessitated the use of higher doses in mice to match the immunogenicity of wild-type viral vectors. VLPs and NYVAC-KC vectors were tested in mice, ultimately showing that the best antibody and Gag-specific T cell responses were generated when both components were administered simultaneously. Thus, plant-produced VLPs and poxvirus vectors represent a highly immunogenic HIV-1 vaccine candidate that warrants further study.
ContributorsMeador, Lydia Rebecca (Author) / Mor, Tsafrir S (Thesis advisor) / Jacobs, Bertram L (Thesis advisor) / Blattman, Joseph N (Committee member) / Mason, Hugh S (Committee member) / Arizona State University (Publisher)
Created2016