Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV
Background: Understanding the mechanism(s) by which broadly neutralizing antibodies (bNAbs) emerge naturally following infection is crucial for the development of a protective vaccine against human immunodeficiency virus (HIV). Although previous studies have implicated high viremia and associated im...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Oxford University Press
2018
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| Online Access: | http://hdl.handle.net/1721.1/118388 https://orcid.org/0000-0002-0050-989X |
| _version_ | 1826217706328686592 |
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| author | Dugast, Anne-Sophie Lofano, Giuseppe Moore, Sarah Hoffner, Michelle Simek, Melissa Poignard, Pascal Seaman, Michael Suscovich, Todd J. Pereyra, Florencia Walker, Bruce D. Kwon, Douglas S. Keele, Brandon F. Alter, Galit Arnold, Kelly Benedict Lauffenburger, Douglas A |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Dugast, Anne-Sophie Lofano, Giuseppe Moore, Sarah Hoffner, Michelle Simek, Melissa Poignard, Pascal Seaman, Michael Suscovich, Todd J. Pereyra, Florencia Walker, Bruce D. Kwon, Douglas S. Keele, Brandon F. Alter, Galit Arnold, Kelly Benedict Lauffenburger, Douglas A |
| author_sort | Dugast, Anne-Sophie |
| collection | MIT |
| description | Background: Understanding the mechanism(s) by which broadly neutralizing antibodies (bNAbs) emerge naturally following infection is crucial for the development of a protective vaccine against human immunodeficiency virus (HIV). Although previous studies have implicated high viremia and associated immune activation as potential drivers for the development of bNAbs, here we sought to unlink the effect of these 2 parameters by evaluating the key inflammatory predictors of bNAb development in HIV-infected individuals who spontaneously control HIV in the absence of antiretroviral therapy (“controllers”).
Methods: The breadth of antibody-mediated neutralization against 11 tier 2 or 3 viruses was assessed in 163 clade B spontaneous controllers of HIV. Plasma levels of 17 cytokines were screened in the same set of subjects. The relationship of the inflammatory signature was assessed in the context of viral blips or viral RNA levels in peripheral blood or gastrointestinal biopsies from aviremic controllers (<50 copies RNA/mL) and in the context of viral sequence diversity analysis in the plasma of viremic controllers (<50–2000 copies RNA/mL).
Results: A unique inflammatory profile, including high plasma levels of CXCL13, sCD40L, IP10, RANTES, and TNFα, was observed in HIV controllers who developed bNAbs. Interestingly, viral load and tissue viremia, but not intermittent viral blips, were associated with these cytokine profiles. However, viral diversity was not significantly associated with increased breadth in controllers.
Conclusion: These results suggest that low antigenic diversity in the setting of a unique inflammatory profile associated with antigen persistence may be linked to the evolution of neutralizing antibody breadth. Keywords: neutralizing antibodies, inflammation, HIV vaccine. |
| first_indexed | 2024-09-23T17:07:52Z |
| format | Article |
| id | mit-1721.1/118388 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T17:07:52Z |
| publishDate | 2018 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/1183882022-09-29T23:52:40Z Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV Dugast, Anne-Sophie Lofano, Giuseppe Moore, Sarah Hoffner, Michelle Simek, Melissa Poignard, Pascal Seaman, Michael Suscovich, Todd J. Pereyra, Florencia Walker, Bruce D. Kwon, Douglas S. Keele, Brandon F. Alter, Galit Arnold, Kelly Benedict Lauffenburger, Douglas A Massachusetts Institute of Technology. Department of Biological Engineering Lauffenburger Arnold, Kelly Benedict Lauffenburger, Douglas A Background: Understanding the mechanism(s) by which broadly neutralizing antibodies (bNAbs) emerge naturally following infection is crucial for the development of a protective vaccine against human immunodeficiency virus (HIV). Although previous studies have implicated high viremia and associated immune activation as potential drivers for the development of bNAbs, here we sought to unlink the effect of these 2 parameters by evaluating the key inflammatory predictors of bNAb development in HIV-infected individuals who spontaneously control HIV in the absence of antiretroviral therapy (“controllers”). Methods: The breadth of antibody-mediated neutralization against 11 tier 2 or 3 viruses was assessed in 163 clade B spontaneous controllers of HIV. Plasma levels of 17 cytokines were screened in the same set of subjects. The relationship of the inflammatory signature was assessed in the context of viral blips or viral RNA levels in peripheral blood or gastrointestinal biopsies from aviremic controllers (<50 copies RNA/mL) and in the context of viral sequence diversity analysis in the plasma of viremic controllers (<50–2000 copies RNA/mL). Results: A unique inflammatory profile, including high plasma levels of CXCL13, sCD40L, IP10, RANTES, and TNFα, was observed in HIV controllers who developed bNAbs. Interestingly, viral load and tissue viremia, but not intermittent viral blips, were associated with these cytokine profiles. However, viral diversity was not significantly associated with increased breadth in controllers. Conclusion: These results suggest that low antigenic diversity in the setting of a unique inflammatory profile associated with antigen persistence may be linked to the evolution of neutralizing antibody breadth. Keywords: neutralizing antibodies, inflammation, HIV vaccine. Bill & Melinda Gates Foundation (OPP1066973) Bill & Melinda Gates Foundation (OPP1032817) National Institutes of Health (U.S.) (R01 AI080289) National Institutes of Health (U.S.) (R01 A102660-01) National Institutes of Health (U.S.) (R37 AI080289-06A1) Ragon Institute of MGH, MIT and Harvard 2018-10-09T15:14:51Z 2018-10-09T15:14:51Z 2017-02 Article http://purl.org/eprint/type/JournalArticle 1058-4838 1537-6591 http://hdl.handle.net/1721.1/118388 Dugast, Anne-Sophie, et al. “Virus-Driven Inflammation Is Associated With the Development of BNAbs in Spontaneous Controllers of HIV.” Clinical Infectious Diseases, vol. 64, no. 8, Apr. 2017, pp. 1098–104. https://orcid.org/0000-0002-0050-989X en_US https://doi.org/10.1093/cid/cix057 Clinical Infectious Diseases Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Oxford University Press Prof. Lauffenburger via Howard Silver |
| spellingShingle | Dugast, Anne-Sophie Lofano, Giuseppe Moore, Sarah Hoffner, Michelle Simek, Melissa Poignard, Pascal Seaman, Michael Suscovich, Todd J. Pereyra, Florencia Walker, Bruce D. Kwon, Douglas S. Keele, Brandon F. Alter, Galit Arnold, Kelly Benedict Lauffenburger, Douglas A Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV |
| title | Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV |
| title_full | Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV |
| title_fullStr | Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV |
| title_full_unstemmed | Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV |
| title_short | Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV |
| title_sort | virus driven inflammation is associated with the development of bnabs in spontaneous controllers of hiv |
| url | http://hdl.handle.net/1721.1/118388 https://orcid.org/0000-0002-0050-989X |
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