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Long lived multi-isotype anti-HIV antibody responses following a prime-double boost immunization strategy
journal contribution
posted on 2005-03-31, 00:00 authored by John StambasJohn Stambas, S Brown, A Gutierrez, R Sealy, W Yue, B Jones, T Lockey, A Zirkel, P Freiden, B Brown, S Surman, C Coleclough, K Slobod, P Doherty, J HurwitzDespite decades of work, an effective HIV vaccine remains elusive. In an effort to elicit protective immunity, investigators have sought to define vaccines able to elicit durable HIV-specific B-cell and T-cell activities. Additionally, vaccines are sought which can induce antibodies of a variety of isotypes, as each isotype possesses unique attributes in terms of opsonization, Fc receptor binding capacity, complement fixation and location. One prominent new vaccine strategy, applied to numerous distinct antigenic systems is the prime boost-regimen, with DNA, vaccinia virus (VV), and/or purified recombinant protein. To examine the durability, location and isotype distribution of responses induced by prime-boost regimens, we tested successive immunizations with DNA, VV and protein (D-V-P), comparing three forms of protein inoculations: (i) purified protein administered intramuscularly with complete Freunds adjuvant, (ii) purified protein administered intranasally, and (iii) purified protein conjugated to oxidized mannan, administered intranasally. We found that all three protocols elicited serum antibodies of multiple isotypes, with serum IgA being most prominent among mice immunized with mannan-conjugated protein. All D-V-P protocols, regardless of protein form or route, also elicited antibody responses at mucosal surfaces. In bronchoalveolar lavage, a tendency toward IgA production was again most prominent in mice boosted with the protein–mannan conjugate. Both B-cell and T-cell responses were sustained for more than 1 year post-immunization following each form of vaccination. Contemporaneous with long-lasting serum and mucosal antibodies were antibody forming cells in the bone marrow of primed animals. Results highlight the D-V-P vaccination strategy as a promising approach for attaining durable, multi-isotype B-cell and T-cell activities toward HIV.
History
Journal
VaccineVolume
23Issue
19Pagination
2454 - 2464Publisher
Elsevier Ltd.Location
Guildford, EnglandPublisher DOI
ISSN
0264-410XeISSN
1873-2518Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
Copyright 2004 Elsevier Ltd All rights reserved.Usage metrics
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prime-boost regimendurableserum\/mucosalScience & TechnologyLife Sciences & BiomedicineImmunologyMedicine, Research & ExperimentalResearch & Experimental MedicineSIMIAN IMMUNODEFICIENCY VIRUSHUMORAL IMMUNE-RESPONSESB-CELL CLONESVACCINIA VIRUSNEUTRALIZATION SEROTYPESPROTECTIVE EFFICACYENV GLYCOPROTEINSDNA IMMUNIZATIONMANNOSE RECEPTORDENDRITIC CELLS
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