دورية أكاديمية
HIV-1 p24(gag) derived conserved element DNA vaccine increases the breadth of immune response in mice.
| العنوان: | HIV-1 p24(gag) derived conserved element DNA vaccine increases the breadth of immune response in mice. |
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| المؤلفون: | Viraj Kulkarni, Margherita Rosati, Antonio Valentin, Brunda Ganneru, Ashish K Singh, Jian Yan, Morgane Rolland, Candido Alicea, Rachel Kelly Beach, Gen-Mu Zhang, Sylvie Le Gall, Kate E Broderick, Niranjan Y Sardesai, David Heckerman, Beatriz Mothe, Christian Brander, David B Weiner, James I Mullins, George N Pavlakis, Barbara K Felber |
| المصدر: | PLoS ONE, Vol 8, Iss 3, p e60245 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Viral diversity is considered a major impediment to the development of an effective HIV-1 vaccine. Despite this diversity, certain protein segments are nearly invariant across the known HIV-1 Group M sequences. We developed immunogens based on the highly conserved elements from the p24(gag) region according to two principles: the immunogen must (i) include strictly conserved elements of the virus that cannot mutate readily, and (ii) exclude both HIV regions capable of mutating without limiting virus viability, and also immunodominant epitopes located in variable regions. We engineered two HIV-1 p24(gag) DNA immunogens that express 7 highly Conserved Elements (CE) of 12-24 amino acids in length and differ by only 1 amino acid in each CE ('toggle site'), together covering >99% of the HIV-1 Group M sequences. Altering intracellular trafficking of the immunogens changed protein localization, stability, and also the nature of elicited immune responses. Immunization of C57BL/6 mice with p55(gag) DNA induced poor, CD4(+) mediated cellular responses, to only 2 of the 7 CE; in contrast, vaccination with p24CE DNA induced cross-clade reactive, robust T cell responses to 4 of the 7 CE. The responses were multifunctional and composed of both CD4(+) and CD8(+) T cells with mature cytotoxic phenotype. These findings provide a method to increase immune response to universally conserved Gag epitopes, using the p24CE immunogen. p24CE DNA vaccination induced humoral immune responses similar in magnitude to those induced by p55(gag), which recognize the virus encoded p24(gag) protein. The inclusion of DNA immunogens composed of conserved elements is a promising vaccine strategy to induce broader immunity by CD4(+) and CD8(+) T cells to additional regions of Gag compared to vaccination with p55(gag) DNA, achieving maximal cross-clade reactive cellular and humoral responses. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC3610668?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0060245 |
| URL الوصول: | https://doaj.org/article/6e5bcd65126b4ecd85d70afccbff0b95 |
| رقم الأكسشن: | edsdoj.6e5bcd65126b4ecd85d70afccbff0b95 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0060245 |