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NOVEL GLIOMA-SPECIFIC VACCINE FOR PEDIATRIC AND YOUNG-ADULT PATIENTS

UCSF researchers have developed a vaccine against pediatric gliomas by targeting a novel epitope.  

Collaboration Opportunity: Novel Mouse Models of Human Hepatitis B Virus Infection for Drug Discovery and Vaccine Research

HBV infection can lead to chronic infections that result in 0.6 million deaths per year worldwide by causing liver failure and cancer. Clearance of HBV infection is age dependent, with the majority of adult-acquired infections leading to spontaneous clearance, whereas infection in young children often leads to chronic infections. To study these early events of infection and immune activation that lead to HBV clearance or persistence, in vivo models are needed to screen and validate lead drug candidates. HBV cannot infect mice, however, researchers at UCSF have generated transgenic mouse models that mimic critical features of primary HBV infection observed in humans.

Novel, Immunogenic Epitopes for use in an HIV Vaccine

The Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate maker that could be used to target any HIV-infected cell regardless of its mutational status. In this regard, scientists have recently focused their attention on so-called cryptic peptides of HIV.  Cryptic peptides are non-functional HIV proteins that are produced due to translational errors that occur in HIV-infected cells.  Because these cryptic peptides are commonly produced and then presented on the surface of the HIV-infected cells, it is thought they may be good surrogate markers and targets for any HIV-infected cell.

Novel Peptides for Development of HIV Vaccine and Therapy

Human Immunodeficiency Virus (HIV) has evolved a number of mechanisms of evading the human immune system.  One way is through a high level of mutation, which makes it difficult to develop a vaccine that stimulates protective immunity against all of the different HIV variants.  Therefore, scientists are searching for a general surrogate marker that could be used to target any HIV-infected cell regardless of its mutational status. In this regard, scientists have recently turned their attention to the APOBEC machinery in HIV cells.  APOBEC proteins are human proteins that modify genetic material of viruses so that they are unable to produce proteins essential for viral survival.  Remarkably, HIV evades the APOBEC defense by making a protein called Vif that re-routes APOBEC proteins to proteosomes for destruction thereby reducing APOBEC's protective functions.  However, this activity also increases the presentation of APOBEC antigens or peptides on the cell's surface. APOBEC peptides may be good candidates for surrogate HIV markers simply because they are present on the surface of all HIV-infected cells.  In addition, in order for HIV-infected cells to stop displaying APOBEC peptides on their surface, the virus would need to evolve mutations in the region coding for the Vif protein that re-routes the APOBEC proteins.  This would make the virus vulnerable to the defenses mediated by the functional APOBEC proteins.  This phenomenon should result in dual pressure on the virus that should slow or prevent the evolution of viral resistance to these T-cell responses.

Apicoplast-Deficient, Attenuated Strains of Plasmodium for Use as Malaria Vaccines

Currently, no malaria vaccines are available for clinical use. The need for a vaccine is also compounded by the emergence of multiple drug-resistant Plasmodium strains. In 2008, there were nearly 250 million cases of malaria and one million deaths worldwide according to the World Health Organization. Moreover, in addition to chloroquine resistance, resistance to newer anti-malarials is growing. Thus, innovative vaccines and anti-malarials are needed to reduce the morbidity and mortality caused by malaria infections in humans.

HUMAN IMMUNOSTIMULATORY T CELLS

Research into modulating immune function through immunostimulatory T cells has been hampered by the lack of identification of the molecular markers on such cells. UCSF investigators have identified a novel endogenous human T cell population that can significantly enhance the proliferative capacity of a T cell response. In contrast to T cells that can be induced to suppress a proliferative response, these are a naturally occurring, functionally mature T-cell subpopulation that induce the proliferation of a T cell.

Methods for Enhancing the Production of Viral Vaccines in Cell Culture

UCSF investigators have developed the methods to significantly enhance the viral yield of infected cell cultures. These methods rely on the inhibition of interferon-stimulated genes, especially double-stranded RNA (dsRNA) dependent kinase (PKR). This method can be used in a wide variety of common cell lines and to produce a wide variety of viruses, including polio, measles, mumps, rubella, hepatitis A, and influenza.

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