دورية أكاديمية
Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice
| العنوان: | Non-neutralizing antibodies targeting the immunogenic regions of HIV-1 envelope reduce mucosal infection and virus burden in humanized mice |
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| المؤلفون: | Hioe, C.E., Li, G., Liu, X., Tsahouridis, O., He, X., Funaki, M., Klingler, J., Tang, A.F., Feyznezhad, R., Heindel, D.W., Wang, X.-H, Spencer, D.A., Hu, G., Satija, N., Prévost, J., Finzi, A., Hessell, A.J., Wang, S., Lu, S., Chen, B.K., Zolla-Pazner, S., Upadhyay, C., Alvarez, R., Su, L. |
| المصدر: | PLoS Pathogens, 18(1) |
| بيانات النشر: | Public Library of Science |
| سنة النشر: | 2022 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | flow cytometry, animal experiment, mucosa inflammation, antibody dependent cellular cytotoxicity, gene expression, antiretroviral therapy, complement activation, complement dependent cytotoxicity, binding affinity, enzyme linked immunosorbent assay, luciferase assay, virus transmission, infection risk, natural killer cell, hematopoietic stem cell, phagocytosis, Human immunodeficiency virus 1, upregulation, genetic transfection, virus load, controlled study, IC50, nonhuman, interferometry, in vitro study, animal cell, Human immunodeficiency virus infection, virus neutralization, T lymphocyte activation, limit of detection |
| الوصف: | Antibodies are principal immune components elicited by vaccines to induce protection from microbial pathogens. In the Thai RV144 HIV-1 vaccine trial, vaccine efficacy was 31% and the sole primary correlate of reduced risk was shown to be vigorous antibody response targeting the V1V2 region of HIV-1 envelope. Antibodies against V3 also were inversely correlated with infection risk in subsets of vaccinees. Antibodies recognizing these regions, however, do not exhibit potent neutralizing activity. Therefore, we examined the antiviral potential of poorly neutralizing monoclonal antibodies (mAbs) against immunodominant V1V2 and V3 sites by passive administration of human mAbs to humanized mice engrafted with CD34+ hematopoietic stem cells, followed by mucosal challenge with an HIV-1 infectious molecular clone expressing the envelope of a tier 2 resistant HIV-1 strain. Treatment with anti-V1V2 mAb 2158 or anti-V3 mAb 2219 did not prevent infection, but V3 mAb 2219 displayed a superior potency compared to V1V2 mAb 2158 in reducing virus burden. While these mAbs had no or weak neutralizing activity and elicited undetectable levels of antibody-dependent cellular cytotoxicity (ADCC), V3 mAb 2219 displayed a greater capacity to bind virus- and cell-associated HIV-1 envelope and to mediate antibody-dependent cellular phagocytosis (ADCP) and C1q complement binding as compared to V1V2 mAb 2158. Mutations in the Fc region of 2219 diminished these effector activities in vitro and lessened virus control in humanized mice. These results demonstrate the importance of Fc functions other than ADCC for antibodies without potent neutralizing activity. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/yath-v230Test; https://cdr.lib.unc.edu/downloads/b56452268?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/b56452268Test |
| DOI: | 10.17615/yath-v230 |
| الإتاحة: | https://doi.org/10.17615/yath-v230Test https://cdr.lib.unc.edu/downloads/b56452268?file=thumbnailTest https://cdr.lib.unc.edu/downloads/b56452268Test |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.17688116 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/yath-v230 |
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