Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1
IntroductionNeutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge.ObjectiveThis study sought to te...
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1271686/full |
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| author | Catarina E. Hioe Catarina E. Hioe Xiaomei Liu Andrew N. Banin Daniel W. Heindel Jéromine Klingler Priyanka G. Rao Christina C. Luo Xunqing Jiang Shilpi Pandey Tracy Ordonez Philip Barnette Maxim Totrov Jiang Zhu Arthur Nádas Susan Zolla-Pazner Chitra Upadhyay Xiaoying Shen Xiang-Peng Kong Ann J. Hessell |
| author_facet | Catarina E. Hioe Catarina E. Hioe Xiaomei Liu Andrew N. Banin Daniel W. Heindel Jéromine Klingler Priyanka G. Rao Christina C. Luo Xunqing Jiang Shilpi Pandey Tracy Ordonez Philip Barnette Maxim Totrov Jiang Zhu Arthur Nádas Susan Zolla-Pazner Chitra Upadhyay Xiaoying Shen Xiang-Peng Kong Ann J. Hessell |
| author_sort | Catarina E. Hioe |
| collection | DOAJ |
| description | IntroductionNeutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge.ObjectiveThis study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env).MethodsFour groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope in vitro.ResultsRabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses.ConclusionThese data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158. |
| first_indexed | 2024-03-11T10:57:34Z |
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| id | doaj.art-bd3b1a8708a244ec9f1494a4fcb1f13f |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T10:57:34Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bd3b1a8708a244ec9f1494a4fcb1f13f2023-11-13T04:57:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12716861271686Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1Catarina E. Hioe0Catarina E. Hioe1Xiaomei Liu2Andrew N. Banin3Daniel W. Heindel4Jéromine Klingler5Priyanka G. Rao6Christina C. Luo7Xunqing Jiang8Shilpi Pandey9Tracy Ordonez10Philip Barnette11Maxim Totrov12Jiang Zhu13Arthur Nádas14Susan Zolla-Pazner15Chitra Upadhyay16Xiaoying Shen17Xiang-Peng Kong18Ann J. Hessell19Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesResearch Service, James J. Peters VA Medical Center, Bronx, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, United StatesDivision of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesDivision of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesDivision of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesMolsoft L.L.C., San Diego, CA, United StatesDepartment of Integrative Structural and Computational Biology and Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, United StatesDepartment of Environment Medicine, New York University Grossman School of Medicine, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesDivision of Surgical Sciences, Department of Surgery, Duke University School of Medicine, Durham, NC, United StatesDepartment of Biochemistry and Molecular Pharmacology, New York University Grossman School of Medicine, New York, NY, United StatesDivision of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, United StatesIntroductionNeutralizing antibodies (Abs) are one of the immune components required to protect against viral infections. However, developing vaccines capable of eliciting neutralizing Abs effective against a broad array of HIV-1 isolates has been an arduous challenge.ObjectiveThis study sought to test vaccines aimed to induce Abs against neutralizing epitopes at the V1V2 apex of HIV-1 envelope (Env).MethodsFour groups of rabbits received a DNA vaccine expressing the V1V2 domain of the CRF01_AE A244 strain on a trimeric 2J9C scaffold (V1V2-2J9C) along with a protein vaccine consisting of an uncleaved prefusion-optimized A244 Env trimer with V3 truncation (UFO-BG.ΔV3) or a V1V2-2J9C protein and their respective immune complexes (ICs). These IC vaccines were made using 2158, a V1V2-specific monoclonal Ab (mAb), which binds the V2i epitope in the underbelly region of V1V2 while allosterically promoting the binding of broadly neutralizing mAb PG9 to its V2 apex epitope in vitro.ResultsRabbit groups immunized with the DNA vaccine and uncomplexed or complexed UFO-BG.ΔV3 proteins (DNA/UFO-UC or IC) displayed similar profiles of Env- and V1V2-binding Abs but differed from the rabbits receiving the DNA vaccine and uncomplexed or complexed V1V2-2J9C proteins (DNA/V1V2-UC or IC), which generated more cross-reactive V1V2 Abs without detectable binding to gp120 or gp140 Env. Notably, the DNA/UFO-UC vaccine elicited neutralizing Abs against some heterologous tier 1 and tier 2 viruses from different clades, albeit at low titers and only in a fraction of animals, whereas the DNA/V1V2-UC or IC vaccines did not. In comparison with the DNA/UFO-UC group, the DNA/UFO-IC group showed a trend of higher neutralization against TH023.6 and a greater potency of V1V2-specific Ab-dependent cellular phagocytosis (ADCP) but failed to neutralize heterologous viruses.ConclusionThese data demonstrate the capacity of V1V2-2J9C-encoding DNA vaccine in combination with UFO-BG.ΔV3, but not V1V2-2J9C, protein vaccines, to elicit homologous and heterologous neutralizing activities in rabbits. The elicitation of neutralizing and ADCP activities was modulated by delivery of UFO-BG.ΔV3 complexed with V2i mAb 2158.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1271686/fullHIV-1 vaccineHIV-1 Envantibodyimmune complex (IC)virus neutralizationADCP |
| spellingShingle | Catarina E. Hioe Catarina E. Hioe Xiaomei Liu Andrew N. Banin Daniel W. Heindel Jéromine Klingler Priyanka G. Rao Christina C. Luo Xunqing Jiang Shilpi Pandey Tracy Ordonez Philip Barnette Maxim Totrov Jiang Zhu Arthur Nádas Susan Zolla-Pazner Chitra Upadhyay Xiaoying Shen Xiang-Peng Kong Ann J. Hessell Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1 Frontiers in Immunology HIV-1 vaccine HIV-1 Env antibody immune complex (IC) virus neutralization ADCP |
| title | Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1 |
| title_full | Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1 |
| title_fullStr | Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1 |
| title_full_unstemmed | Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1 |
| title_short | Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1 |
| title_sort | vaccination with immune complexes modulates the elicitation of functional antibodies against hiv 1 |
| topic | HIV-1 vaccine HIV-1 Env antibody immune complex (IC) virus neutralization ADCP |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1271686/full |
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