scholarly journals Enhanced Mucosal Immunoglobulin A Response of Intranasal Adenoviral Vector Human Immunodeficiency Virus Vaccine and Localization in the Central Nervous System

2003 ◽  
Vol 77 (18) ◽  
pp. 10078-10087 ◽  
Author(s):  
Franck Lemiale ◽  
Wing-pui Kong ◽  
Levent M. Akyürek ◽  
Xu Ling ◽  
Yue Huang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Viral Vector ◽  
Recombinant Adenovirus ◽  
Immunoglobulin A ◽  
Retrograde Transport ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Hiv 1

ABSTRACT Replication-defective adenovirus (ADV) vectors represent a promising potential platform for the development of a vaccine for AIDS. Although this vector is typically administered intramuscularly, it would be desirable to induce mucosal immunity by delivery through alternative routes. In this study, the immune response and biodistribution of ADV vectors delivered by different routes were evaluated. ADV vectors expressing human immunodeficiency virus type 1 (HIV-1) Gag, Pol, and Env were delivered intramuscularly or intranasally into mice. Intranasal immunization induced greater HIV-specific immunoglobulin A (IgA) responses in mucosal secretions and sera than in animals with intramuscular injection, which showed stronger systemic cellular and IgG responses. Administration of the vaccine through an intranasal route failed to overcome prior ADV immunity. Animals exposed to ADV prior to vaccination displayed substantially reduced cellular and humoral immune responses to HIV antigens in both groups, though the reduction was greater in animals immunized intranasally. This inhibition was partially overcome by priming with a DNA expression vector expressing HIV-1 Gag, Pol, and Env before boosting with the viral vector. Biodistribution of recombinant adenovirus (rADV) vectors administered intranasally revealed infection of the central nervous system, specifically in the olfactory bulb, possibly via retrograde transport by olfactory neurons in the nasal epithelium, which may limit the utility of this route of delivery of ADV vector-based vaccines.

scholarly journals Human immunodeficiency virus type 1 infection of the brain.

1993 ◽  
Vol 6 (4) ◽  
pp. 339-366 ◽  
Author(s):  
W J Atwood ◽  
J R Berger ◽  
R Kaderman ◽  
C S Tornatore ◽  
E O Major
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Early Years ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Hiv 1

Direct infection of the central nervous system by human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, was not appreciated in the early years of the AIDS epidemic. Neurological complications associated with AIDS were largely attributed to opportunistic infections that arose as a result of the immunocompromised state of the patient and to depression. In 1985, several groups succeeded in isolating HIV-1 directly from brain tissue. Also that year, the viral genome was completely sequenced, and HIV-1 was found to belong to a neurotropic subfamily of retrovirus known as the Lentivirinae. These findings clearly indicated that direct HIV-1 infection of the central nervous system played a role in the development of AIDS-related neurological disease. This review summarizes the clinical manifestations of HIV-1 infection of the central nervous system and the related neuropathology, the tropism of HIV-1 for specific cell types both within and outside of the nervous system, the possible mechanisms by which HIV-1 damages the nervous system, and the current strategies for diagnosis and treatment of HIV-1-associated neuropathology.

scholarly journals Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
C. Béguelin ◽  
M. Vázquez ◽  
M. Bertschi ◽  
S. Yerly ◽  
D. de Jong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Viral Suppression ◽  
Multidrug Resistant ◽  
Viral Escape ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
Cns Penetration ◽  
Hiv 1

Abstract In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.

scholarly journals Human Immunodeficiency Virus Type 1 RNA Detected in the Central Nervous System (CNS) After Years of Suppressive Antiretroviral Therapy Can Originate from a Replicating CNS Reservoir or Clonally Expanded Cells

2018 ◽  
Vol 69 (8) ◽  
pp. 1345-1352 ◽  
Author(s):  
Sarah B Joseph ◽  
Laura P Kincer ◽  
Natalie M Bowman ◽  
Chris Evans ◽  
Michael J Vinikoor ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Human Immunodeficiency Virus ◽  
Nervous System ◽  
Antiretroviral Therapy ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Csf Escape

Abstract Background Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations may reveal whether they are produced by central nervous system (CNS) reservoirs. Methods We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points. Results For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity. Conclusions Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.

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