Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques
CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vacc...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/89395 |
| _version_ | 1797300068830674944 |
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| author | Anil Verma Chase E Hawes Sonny R Elizaldi Justin C Smith Dhivyaa Rajasundaram Gabriel Kristian Pedersen Xiaoying Shen LaTonya D Williams Georgia D Tomaras Pamela A Kozlowski Rama R Amara Smita S Iyer |
| author_facet | Anil Verma Chase E Hawes Sonny R Elizaldi Justin C Smith Dhivyaa Rajasundaram Gabriel Kristian Pedersen Xiaoying Shen LaTonya D Williams Georgia D Tomaras Pamela A Kozlowski Rama R Amara Smita S Iyer |
| author_sort | Anil Verma |
| collection | DOAJ |
| description | CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA +QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml- MPLA; 5500; CAF01, 2155; p<0.05). Notably, interferon γ+Env-specific Tfh responses were consistently higher with gp140 in MPLA +QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC Tfh1 induction promote persistent Env antibodies, important for protective immunity against HIV. |
| first_indexed | 2024-03-07T23:01:53Z |
| format | Article |
| id | doaj.art-25f016ab6a0344d78af967a9cbf3f47a |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-07T23:01:53Z |
| publishDate | 2024-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-25f016ab6a0344d78af967a9cbf3f47a2024-02-22T13:31:44ZengeLife Sciences Publications LtdeLife2050-084X2024-02-011210.7554/eLife.89395Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaquesAnil Verma0Chase E Hawes1Sonny R Elizaldi2Justin C Smith3https://orcid.org/0000-0001-7702-7920Dhivyaa Rajasundaram4Gabriel Kristian Pedersen5Xiaoying Shen6LaTonya D Williams7Georgia D Tomaras8Pamela A Kozlowski9Rama R Amara10Smita S Iyer11https://orcid.org/0000-0002-8918-7005Department of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United StatesGraduate Group in Immunology, University of California, Davis, Davis, United States; California National Primate Research Center, University of California, Davis, Davis, United StatesGraduate Group in Immunology, University of California, Davis, Davis, United States; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, United StatesDepartment of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, United StatesBioinformatics Core, Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, Pittsburgh, United StatesStatens Serum Institute, Copenhagen, DenmarkCenter for Human Systems Immunology, Durham, United States; Department of Surgery, Duke University Medical Center, Durham, United States; Duke Human Vaccine Institute, Duke University Medical Center, Durham, United StatesCenter for Human Systems Immunology, Durham, United States; Department of Surgery, Duke University Medical Center, Durham, United States; Duke Human Vaccine Institute, Duke University Medical Center, Durham, United StatesCenter for Human Systems Immunology, Durham, United States; Department of Surgery, Duke University Medical Center, Durham, United States; Duke Human Vaccine Institute, Duke University Medical Center, Durham, United States; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States; Department of Integrative Immunobiology, Duke University Medical Center, Durham, United StatesDepartment of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, United StatesDepartment of Microbiology and Immunology, Emory University, Atlanta, United States; Yerkes National Primate Research Center, Emory University, Atlanta, United StatesDepartment of Pathology, School of Medicine, University of Pittsburgh, Pittsburgh, United States; California National Primate Research Center, University of California, Davis, Davis, United States; Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, United StatesCD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA +QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml- MPLA; 5500; CAF01, 2155; p<0.05). Notably, interferon γ+Env-specific Tfh responses were consistently higher with gp140 in MPLA +QS-21 and positively correlated with Env antibody persistence. These findings suggest that vaccine platforms maximizing GC Tfh1 induction promote persistent Env antibodies, important for protective immunity against HIV.https://elifesciences.org/articles/89395T-dependent B cell responseantibody persistencevaccine efficacy |
| spellingShingle | Anil Verma Chase E Hawes Sonny R Elizaldi Justin C Smith Dhivyaa Rajasundaram Gabriel Kristian Pedersen Xiaoying Shen LaTonya D Williams Georgia D Tomaras Pamela A Kozlowski Rama R Amara Smita S Iyer Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques eLife T-dependent B cell response antibody persistence vaccine efficacy |
| title | Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques |
| title_full | Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques |
| title_fullStr | Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques |
| title_full_unstemmed | Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques |
| title_short | Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques |
| title_sort | tailoring tfh profiles enhances antibody persistence to a clade c hiv 1 vaccine in rhesus macaques |
| topic | T-dependent B cell response antibody persistence vaccine efficacy |
| url | https://elifesciences.org/articles/89395 |
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