scholarly journals The Potential of eCD4-Ig, Delivered by Adeno-Associated Virus (AAV) Vector as a Novel Vaccine for HIV/AIDS Infection

2021 ◽  
Vol 2 (2) ◽  
pp. 133-9
Author(s):  
Ghea Mangkuliguna
Keyword(s):  
Hiv Infection ◽  
Immunoglobulin G ◽  
Rhesus Macaques ◽  
Therapeutic Vaccine ◽  
Hiv Vaccine ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
Dependent Cell ◽  
Hiv Aids

Background: HIV/AIDS has already become one of the world's major health issues taking its toll on millions of lives each year. Developing an HIV vaccine with excellent efficacy has become a global urgency that must be addressed immediately. Recently, researchers have successfully developed a more self-like molecule which is a fusion protein between human CD4 domains and immunoglobulin G (IgG) Fc with a CCR5-mimetic sulfopeptide in the carboxy terminus. This molecule, eCD4-Ig, targets only the conserved regions of HIV Env and thus demonstrated the most remarkable potency and breadth so far. By using adeno-associated virus (AAV) vector, eCD4-Ig’s long-term expression in vivo can be achieved. Objectives: Evaluate the efficacy of AAV-eCD4-Ig as both preventive and therapeutic vaccine for HIV/AIDS infection. Methods: A systematic literature study was conducted with the database in PubMed, ScienceDirect, and Proquest. No time and language restriction were applied. Discussion: This review shows that eCD4-Ig eliminates HIV-infected cells through neutralization and antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, eCD4-Ig is also capable of preventing HIV infection in vivo. Delivered with AAV, eCD4-Ig is maintained stably at both protective and therapeutic levels, as well as gives robust protection for rhesus macaques for almost a year long through a single injection. Conclusion: This study offers evidences that AAV-eCD4-Ig appears to have the potential to be an effective vaccine to prevent HIV infection. Keywords: AAV, AIDS, eCD4-Ig, HIV, vaccine   Latar Belakang: Pengembangan vaksin HIV yang efektif menjadi sangat penting mengingat tingginya angka kematian yang ditimbulkan oleh HIV/AIDS. Beberapa tahun terakhir, peneliti berhasil menemukan sebuah molekul yang tersusun atas domain CD4 manusia, immunoglobulin G (IgG) Fc, dan sulfopeptida yang menyerupai CCR5. Molekul yang dinamakan eCD4-Ig ini menargetkan area konservatif dari HIV Env sehingga berpotensi untuk menjadi vaksin HIV yang efektif. Ekspresi eCD4-Ig akan dipertahankan menggunakan Adeno-associated Virus Vector (AAV). Tujuan: Evaluasi efektivitas AAV-eCD4-Ig sebagai vaksin untuk HIV/AIDS. Metode: Penelitian dilakukan dengan melakukan tinjauan pustaka dari beberapa database jurnal, yakni PubMed, ScienceDirect, dan Proquest tanpa ada batasan waktu dan bahasa. Pembahasan: eCD4-Ig membunuh sel-sel yang terinfeksi HIV melalui proses netralisasi dan antibody-dependent cell-mediated cytotoxicity (ADCC). eCD4-Ig juga memberikan perlindungan terhadap infeksi HIV. Ekspresi AAV-eCD4-Ig sangat stabil untuk dosis protektif dan terapeutik, sekaligus melindungi rhesus macaques dari infeksi HIV selama hampir 1 tahun lamanya hanya dengan sekali injeksi. Kesimpulan: AAV-eCD4-Ig memiliki potensi yang menjanjikan untuk menjadi vaksin HIV yang efektif bagi seluruh penderita HIV/AIDS di seluruh dunia. Kata Kunci: AAV, AIDS, eCD4-Ig, HIV, vaksin

Adeno-associated virus (AAV) vector antisense gene transfer in vivo decreases GABAAα1 containing receptors and increases inferior collicular seizure sensitivity

1997 ◽  
Vol 756 (1-2) ◽  
pp. 76-83 ◽  
Author(s):  
Xiao Xiao ◽  
Thomas J McCown ◽  
Juan Li ◽  
George R Breese ◽  
A.Leslie Morrow ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Antisense Gene ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
Inferior Collicular

scholarly journals Simian-Human Immunodeficiency Virus SHIV.CH505 Infection of Rhesus Macaques Results in Persistent Viral Replication and Induces Intestinal Immunopathology

2019 ◽  
Vol 93 (18) ◽  
Author(s):  
Katharine J. Bar ◽  
Ernesto Coronado ◽  
Tiffany Hensley-McBain ◽  
Megan A. O’Connor ◽  
Jessica M. Osborn ◽  
...  
Keyword(s):  
T Cells ◽  
Hiv Infection ◽  
Viral Replication ◽  
Cell Function ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Subtype C ◽  
Viral Kinetics ◽  
Hiv 1

ABSTRACTSimian-human immunodeficiency viruses (SHIVs) have been utilized to test vaccine efficacy and characterize mechanisms of viral transmission and pathogenesis. However, the majority of SHIVs currently available have significant limitations in that they were developed using sequences from chronically HIV-infected individuals or uncommon HIV subtypes or were optimized for the macaque model by serially passaging the engineered virusin vitroorin vivo. Recently, a newly developed SHIV, SHIV.C.CH505.375H.dCT (SHIV.CH505), which incorporates vpu-env (gp140) sequences from a transmitted/founder HIV-1 subtype C strain, was shown to retain attributes of primary HIV-1 strains. However, a comprehensive analysis of the immunopathology that results from infection with this virus, especially in critical tissue compartments like the intestinal mucosa, has not been completed. In this study, we evaluated the viral dynamics and immunopathology of SHIV.CH505 in rhesus macaques. In line with previous findings, we found that SHIV.CH505 is capable of infecting and replicating efficiently in rhesus macaques, resulting in peripheral viral kinetics similar to that seen in pathogenic SIV and HIV infection. Furthermore, we observed significant and persistent depletions of CCR5+and CCR6+CD4+T cells in mucosal tissues, decreases in CD4+T cells producing Th17 cell-associated cytokines, CD8+T cell dysfunction, and alterations of B cell and innate immune cell function, indicating that SHIV.CH505 elicits intestinal immunopathology typical of SIV/HIV infection. These findings suggest that SHIV.CH505 recapitulates the early viral replication dynamics and immunopathogenesis of HIV-1 infection of humans and thus can serve as a new model for HIV-1 pathogenesis, treatment, and prevention research.IMPORTANCEThe development of chimeric SHIVs has been instrumental in advancing our understanding of HIV-host interactions and allowing forin vivotesting of novel treatments. However, many of the currently available SHIVs have distinct drawbacks and are unable to fully reflect the features characteristic of primary SIV and HIV strains. Here, we utilize rhesus macaques to define the immunopathogenesis of the recently developed SHIV.CH505, which was designed without many of the limitations of previous SHIVs. We observed that infection with SHIV.CH505 leads to peripheral viral kinetics and mucosal immunopathogenesis comparable with those caused by pathogenic SIV and HIV. Overall, these data provide evidence of the value of SHIV.CH505 as an effective model of SIV/HIV infection and an important tool that can be used in future studies, including preclinical testing of new therapies or prevention strategies.

scholarly journals Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid

Gene Therapy ◽  
2020 ◽  
Vol 27 (9) ◽  
pp. 427-434
Author(s):  
Ryota Watano ◽  
Tsukasa Ohmori ◽  
Shuji Hishikawa ◽  
Asuka Sakata ◽  
Hiroaki Mizukami
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Transgene Expression ◽  
Imaging System ◽  
Standard Dose ◽  
Neutralizing Antibody ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
In Vivo Imaging System

Abstract Adeno-associated virus (AAV) vectors can transduce hepatocytes efficiently in vivo in various animal species, including humans. Few reports, however, have examined the utility of pigs in gene therapy. Pigs are potentially useful in preclinical studies because of their anatomical and physiological similarity to humans. Here, we evaluated the utility of microminipigs for liver-targeted gene therapy. These pigs were intravenously inoculated with an AAV8 vector encoding the luciferase gene, and gene expression was assessed by an in vivo imaging system. Robust transgene expression was observed almost exclusively in the liver, even though the pig showed a low-titer of neutralizing antibody (NAb) against the AAV8 capsid. We assessed the action of NAbs against AAV, which interfere with AAV vector-mediated gene transfer by intravascular delivery. When a standard dose of vector was administered intravenously, transgene expression was observed in both NAb-negative and low-titer (14×)-positive subjects, whereas gene expression was not observed in animals with higher titers (56×). These results are compatible with our previous observations using nonhuman primates, indicating that pigs are useful in gene therapy experiments, and that the role of low-titer NAb in intravenous administration of the AAV vector shows similarities across species.

scholarly journals A mosaic adeno-associated virus vector as a versatile tool that exhibits high levels of transgene expression and neuron specificity in primate brain

2021 ◽  
Author(s):  
Kei Kimura ◽  
Yuji Nagai ◽  
Gaku Hatanaka ◽  
Yang Fang ◽  
Andi Zheng ◽  
...  
Keyword(s):  
Transgene Expression ◽  
Gene Transduction ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
Macaque Monkeys ◽  
Primate Brain ◽  
Versatile Tool ◽  
In Vivo Calcium Imaging ◽  
Aav1 Vector

Recent emphasis has been placed on gene transduction mediated through recombinant adeno-associated virus (AAV) vector to manipulate activity of neurons and their circuitry in the primate brain. In the present study, we created a novel AAV vector of which capsid was composed of capsid proteins derived from the serotypes 1 and 2 (AAV1 and AAV2). Following the injection into the frontal cortex of macaque monkeys, this mosaic vector, termed AAV2.1 vector, was found to exhibit the excellence in transgene expression (for the AAV1 vector) and neuron specificity (for the AAV2 vector) simultaneously. To explore its applicability to chemogenetic manipulation and in vivo calcium imaging, the AAV2.1 vector expressing excitatory DREADDs or GCaMP was injected into the striatum or the visual cortex of macaque monkeys, respectively. Our results have defined that such vectors secure intense and stable expression of the target proteins and yield conspicuous modulation and imaging of neuronal activity.

scholarly journals MVA-B AS HIV/AIDS VACCINE CANDIDATE: FROM BASIC SCIENCE TO PROPHYLACTIC AND THERAPEUTIC CLINICAL TRIALS

2020 ◽  
pp. 29-60
Author(s):  
Carmen Elena Gómez Rodríguez
Keyword(s):  
Clinical Trials ◽  
Vaccine Candidate ◽  
Therapeutic Vaccine ◽  
Basic Knowledge ◽  
Antigen Delivery ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1 ◽  
Hiv Aids

The highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA) has reached maturity as antigen delivery system and as a vaccine candidate against a broad spectrum of infectious diseases. This has been largely recognized from research on virus–host cell interactions, gene expression profiling, virus distribution and immunological studies in preclinical and clinical trials. This review includes our main contributions from the basic knowledge of the biology of the MVA vector, both in vitro and in vivo, in comparison with the attenuated NYVAC strain, to its evaluation as a vaccine candidate against HIV/AIDS in clinical trials. We will detail the generation and characterization of the recombinant poxvirus vector MVA expressing the HIV-1 Env, Gag, Pol and Nef antigens from clade B (referred as MVA-B) and review the preclinical data that supported the evaluation of MVA-B as the first in human HIV-1 prophylactic and therapeutic vaccine in Spain. In addition, we will assess the results of clinical trials and discuss the research projects we are currently working on considering the latest scientific advances in the HIV vaccine field.

scholarly journals Full Functional Rescue of a Complete Muscle (TA) in Dystrophic Hamsters by Adeno-Associated Virus Vector-Directed Gene Therapy

2000 ◽  
Vol 74 (3) ◽  
pp. 1436-1442 ◽  
Author(s):  
Xiao Xiao ◽  
Juan Li ◽  
Yeou-Ping Tsao ◽  
Devin Dressman ◽  
Eric P. Hoffman ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Tibialis Anterior Muscle ◽  
Complete Recovery ◽  
Substantial Improvement ◽  
Muscle Weight ◽  
Aav Vector ◽  
Adeno Associated Virus ◽  
Tetanic Force

ABSTRACT Limb girdle muscular dystrophy (LGMD) 2F is caused by mutations in the δ-sarcoglycan (SG) gene. Previously, we have shown successful application of a recombinant adeno-associated virus (AAV) vector for genetic and biochemical rescue in the Bio14.6 hamster, a homologous animal model for LGMD 2F (J. Li et al., Gene Ther. 6:74–82, 1999). In this report, we show efficient and long-term δ-SG expression accompanied by nearly complete recovery of physiological function deficits after a single-dose AAV vector injection into the tibialis anterior muscle of the dystrophic hamsters. AAV vector treatment led to more than 97% recovery in muscle strength for both the specific twitch force and the specific tetanic force, when compared to the age-matched control. Vector treatment also prevented pathological muscle hypertrophy and resulted in normal muscle weight and size. Finally, vector-treated muscle showed substantial improvement of the histopathology. This is the first report of successful functional rescue of an entire muscle after AAV-mediated gene delivery. This report also demonstrates the feasibility of in vivo gene therapy for LGMD patients by using AAV vectors.

Operation Teddy

2003 ◽  
Vol 1 (1) ◽  
pp. 20-28
Author(s):  
Lyndall Ellingson
Keyword(s):  
Health Education ◽  
Service Learning ◽  
Hiv Infection ◽  
Aids Prevention ◽  
Education Curriculum ◽  
Infection Rates ◽  
Community Members ◽  
Education Students ◽  
Prevention Education ◽  
Hiv Aids

Current adolescent HIV infection rates support the need for early HIV/AIDS prevention education. This article describes a successful service-learning project in which undergraduate health education students developed and taught an elementaryschool HIV/AIDS prevention education curriculum that included a compassion component involving donation of teddy bears to community members affected with HIV/AIDS.

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