Author
Dominique Pennick
Bio: Dominique Pennick is an academic researcher from Tufts University. The author has contributed to research in topics: Virus & Viremia. The author has an hindex of 2, co-authored 2 publications receiving 524 citations.
Papers
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TL;DR: Adult macaques do not develop disease after infection with a nef deletion mutant of the simian immunodeficiency virus (SIV) and are protected against challenge with pathogenic virus, but neonatal macaques developed persistently high levels of viremia after oral exposure to SIV nef, vpr, and negative regulatory element (NRE) deletion mutant.
Abstract: Adult macaques do not develop disease after infection with a nef deletion mutant of the simian immunodeficiency virus (SIV) and are protected against challenge with pathogenic virus. This finding led to the proposal to use nef-deleted viruses as live, attenuated vaccines to prevent human acquired immunodeficiency syndrome (AIDS). In contrast, neonatal macaques developed persistently high levels of viremia after oral exposure to and SIV nef, vpr, and negative regulatory element (NRE) deletion mutant. Severe hemolytic anemia, thrombocytopenia, and CD4+ T cell depletion were observed, indicating that neither nef nor vpr determine pathogenicity in neonates. Because such constructs have retained their pathogenic potential, they should not be used as candidate live, attenuated virus vaccines against human AIDS.
512 citations
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TL;DR: The most common indications and the use of radiography, ultrasonography, and scintography in the diagnosis of hepatic disorders in cats are presented.
13 citations
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TL;DR: Investigation of HIV-specific immune responses in HIV-negative individuals who have been exposed to the virus multiple times suggests that natural immune responses to HIV may be protective in rare individuals.
Abstract: Considerable progress has been made recently in understanding the genetic, immunologic, and virologic factors in human immunodeficiency virus (HIV)-infected individuals who either rapidly progress or do not progress to acquired immunodeficiency syndrome (AIDS). In addition, detection of HIV-specific immune responses in HIV-negative individuals who have been exposed to the virus multiple times suggests that natural immune responses to HIV may be protective in rare individuals. Understanding the correlates of protective immunity to HIV infection is critical to efforts to develop preventive HIV vaccines as well as to determine the feasibility of treating HIV infection by boosting immunity to HIV.
457 citations
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TL;DR: The experiments delineate mechanisms involved in species-restricted replication of this lentivirus and show that human cells support both productive- and infective-phase mechanisms of the FIV life cycle needed for efficient lentiviral vector transduction.
Abstract: The molecular bases for species barriers to lentiviral replication are not well understood, but are of interest for explaining lentiviral pathogenesis, devising therapeutic strategies, and adapting lentiviruses to gene therapy. HIV-1-based lentiviral vectors efficiently transduce nondividing cells, but present complex safety concerns. Nonprimate (ungulate or feline) lentiviruses might provide safer alternatives, but these viruses display highly restricted tropisms, and their potential for adaptation as replication-defective vectors capable of transducing human cells is unknown. Feline immunodeficiency virus (FIV) does not infect humans or other non-Felidae despite prevalent natural exposure. Although long terminal repeat (LTR)-directed FIV expression was found to be negligible in human cells, promoter substitution enabled an env-deleted, three-plasmid, human cell-FIV lentiviral vector system to express high levels of FIV proteins and FIV vectors in human cells, thus bypassing the hazards of feline vector producer cells. Pseudotyped FIV vectors efficiently transduced dividing, growth-arrested, and postmitotic human targets. The experiments delineate mechanisms involved in species-restricted replication of this lentivirus and show that human cells support both productive- and infective-phase mechanisms of the FIV life cycle needed for efficient lentiviral vector transduction. Nonprimate lentiviral vectors may offer safety advantages, and FIV vectors provide unique experimental opportunities.
451 citations
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Trinity University1, California National Primate Research Center2, University of California, Davis3, Wake Forest University4, Biomedical Primate Research Centre5, Yerkes National Primate Research Center6, Georgia State University7, University of Washington8, University of Texas Health Science Center at San Antonio9, University of Wisconsin-Madison10, Baylor College of Medicine11
TL;DR: Key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research are reviewed.
Abstract: Research involving nonhuman primates (NHPs) has played a vital role in many of the medical and scientific advances of the past century. NHPs are used because of their similarity to humans in physiology, neuroanatomy, reproduction, development, cognition, and social complexity-yet it is these very similarities that make the use of NHPs in biomedical research a considered decision. As primate researchers, we feel an obligation and responsibility to present the facts concerning why primates are used in various areas of biomedical research. Recent decisions in the United States, including the phasing out of chimpanzees in research by the National Institutes of Health and the pending closure of the New England Primate Research Center, illustrate to us the critical importance of conveying why continued research with primates is needed. Here, we review key areas in biomedicine where primate models have been, and continue to be, essential for advancing fundamental knowledge in biomedical and biological research.
442 citations
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TL;DR: Key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine are reviewed.
Abstract: The development of a safe and effective human immunodeficiency virus (HIV)-1 vaccine is a critically important global health priority. Despite recent advances in our understanding of HIV-1 pathogenesis and immunology, however, major scientific obstacles remain. Prototype HIV-1 vaccine candidates aimed at eliciting humoral and cellular immune responses have so far failed to protect against HIV-1 infection or to reduce viral loads after infection in clinical efficacy studies. A renewed and coordinated commitment to basic discovery research, preclinical studies and clinical trials will therefore be required to overcome the hurdles currently facing the field. Here I review key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine.
435 citations
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TL;DR: The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations, which did not require neutralizing antibody and was active for a series of challenges.
Abstract: Eight different protocols were compared for their ability to raise protection against immunodeficiency virus challenges in rhesus macaques. The most promising containment of challenge infections was achieved by intradermal DNA priming followed by recombinant fowl pox virus booster immunizations. This containment did not require neutralizing antibody and was active for a series of challenges ending with a highly virulent virus with a primary isolate envelope heterologous to the immunizing strain.
391 citations