Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses
| Autor: | Danuta Kozbor, Mitsuo Honda, Yutaro Kaneko, Katsutoshi Komuro, Dariusz Kmieciak, Elizabeth Bolesta, Andrew Wierzbicki, Jaroslaw Gzyl, Toshio Naito |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
DNA vaccine
T cell Molecular Sequence Data Antibody Affinity Heterologous HIV Infections Envelope glycoprotein CD8-Positive T-Lymphocytes Cross Reactions Biology V3 loop Antibodies Viral Neutralizing antibodies Epitope HIV Envelope Protein gp160 DNA vaccination Mice 03 medical and health sciences 0302 clinical medicine Virology Vaccines DNA medicine Animals Avidity Amino Acid Sequence Glycoproteins 030304 developmental biology chemistry.chemical_classification Mice Inbred BALB C 0303 health sciences virus diseases Cellular responses Molecular biology 3. Good health Disease Models Animal medicine.anatomical_structure chemistry HIV-1 Immunization Glycoprotein Gene Deletion Spleen CD8 030215 immunology |
| Zdroj: | Virology. 318:493-506 |
| ISSN: | 0042-6822 |
| Popis: | Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp140(89.6)-derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (DeltaV1/V2) region elicited increased levels of cross-reactive CD8(+) T cell responses. Mice immunized with the mV2/mV3 or DeltaV1/V2/mV3 gp140(89.6) plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and DeltaV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein. |
| Databáze: | OpenAIRE |
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