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Enhanced mucosal immunoglobulin A response of intranasal adenoviral vector human immunodeficiency virus vaccine and localization in the central nervous system.

Journal article
Authors Franck Lemiale
Wing-pui Kong
Levent Akyürek
Xu Ling
Yue Huang
Bimal K Chakrabarti
Michael Eckhaus
Gary J Nabel
Published in Journal of Virology
Volume 77
Issue 18
Pages 10078-87
ISSN 0022-538X
Publication year 2003
Published at Wallenberg Laboratory
Pages 10078-87
Language en
Links dx.doi.org/10.1128/JVI.77.18.10078-...
Keywords AIDS Vaccines, administration & dosage, immunology, Adenoviridae, genetics, immunology, Administration, Intranasal, Animals, Brain, virology, CD8-Positive T-Lymphocytes, immunology, Female, Genetic Vectors, administration & dosage, immunology, Immunization, Immunoglobulin A, Secretory, biosynthesis, Injections, Intramuscular, Interferon Type II, biosynthesis, Mice, Mice, Inbred BALB C, Vaccines, DNA, immunology
Subject categories Medical and Health Sciences

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.

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