A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials

Zoe Moodie; Shuying Sue Li; Elena E. Giorgi; La Tonya D. Williams; One Dintwe; Lindsay N. Carpp; Shiyu Chen; Kelly E. Seaton; Sheetal S. Sawant; Lu Zhang; Jack Heptinstall; Shuying Liu; Nicole Grunenberg; Frank Tomaka; Supachai Rerks-Ngarm; Punnee Pitisuttithum; Sorachai Nitayaphan; Julie A. Ake; Sandhya Vasan; Giuseppe Pantaleo; Ian Frank; Lindsey R. Baden; Paul A. Goepfert; Michael Keefer; Mike Chirenje; Mina C. Hosseinipour; Kathryn Mngadi; Fatima Laher; Nigel Garrett; Linda Gail Bekker; Stephen De Rosa; Erica Andersen-Nissen; James G. Kublin; Shan Lu; Peter B. Gilbert; Glenda E. Gray; Lawrence Corey; M. Juliana McElrath; Georgia D. Tomaras

doi:10.1080/22221751.2025.2485317

A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials

Zoe Moodie^*, Shuying Sue Li, Elena E. Giorgi, La Tonya D. Williams, One Dintwe, Lindsay N. Carpp, Shiyu Chen, Kelly E. Seaton, Sheetal S. Sawant, Lu Zhang, Jack Heptinstall, Shuying Liu, Nicole Grunenberg, Frank Tomaka, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Julie A. Ake, Sandhya Vasan, Giuseppe PantaleoIan Frank, Lindsey R. Baden, Paul A. Goepfert, Michael Keefer, Mike Chirenje, Mina C. Hosseinipour, Kathryn Mngadi, Fatima Laher, Nigel Garrett, Linda Gail Bekker, Stephen De Rosa, Erica Andersen-Nissen, James G. Kublin, Shan Lu, Peter B. Gilbert, Glenda E. Gray, Lawrence Corey, M. Juliana McElrath, Georgia D. Tomaras

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints–providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses–two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines. Trial registration:ClinicalTrials.gov identifier: NCT01799954. Trial registration:ClinicalTrials.gov identifier: NCT02109354. Trial registration:ClinicalTrials.gov identifier: NCT02404311. Trial registration:ClinicalTrials.gov identifier: NCT02207920. Trial registration:ClinicalTrials.gov identifier: NCT02296541. Trial registration:ClinicalTrials.gov identifier: NCT03284710. Trial registration:ClinicalTrials.gov identifier: NCT02915016. Trial registration:ClinicalTrials.gov identifier: NCT02997969. Trial registration:ClinicalTrials.gov identifier: NCT03122223. Trial registration:ClinicalTrials.gov identifier: NCT03409276. Trial registration:ClinicalTrials.gov identifier: NCT02968849. Trial registration:ClinicalTrials.gov identifier: NCT03060629. Trial registration:ClinicalTrials.gov identifier: NCT00223080.

Original language	English
Article number	2485317
Journal	Emerging Microbes and Infections
Volume	14
Issue number	1
DOIs	https://doi.org/10.1080/22221751.2025.2485317
State	Published - 2025
Externally published	Yes

Keywords

Binding antibody multiplex assay
cross-protocol analysis
Env V1V2 binding antibody response breadth score
intracellular cytokine staining
matched polyvalent DNA-polyvalent protein/GLA-SE prime-boost regimen

Access to Document

10.1080/22221751.2025.2485317

Cite this

Moodie, Z., Li, S. S., Giorgi, E. E., Williams, L. T. D., Dintwe, O., Carpp, L. N., Chen, S., Seaton, K. E., Sawant, S. S., Zhang, L., Heptinstall, J., Liu, S., Grunenberg, N., Tomaka, F., Rerks-Ngarm, S., Pitisuttithum, P., Nitayaphan, S., Ake, J. A., Vasan, S., ... Tomaras, G. D. (2025). A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerging Microbes and Infections, 14(1), Article 2485317. https://doi.org/10.1080/22221751.2025.2485317

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title = "A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials",

abstract = "Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints–providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses–two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines. Trial registration:ClinicalTrials.gov identifier: NCT01799954. Trial registration:ClinicalTrials.gov identifier: NCT02109354. Trial registration:ClinicalTrials.gov identifier: NCT02404311. Trial registration:ClinicalTrials.gov identifier: NCT02207920. Trial registration:ClinicalTrials.gov identifier: NCT02296541. Trial registration:ClinicalTrials.gov identifier: NCT03284710. Trial registration:ClinicalTrials.gov identifier: NCT02915016. Trial registration:ClinicalTrials.gov identifier: NCT02997969. Trial registration:ClinicalTrials.gov identifier: NCT03122223. Trial registration:ClinicalTrials.gov identifier: NCT03409276. Trial registration:ClinicalTrials.gov identifier: NCT02968849. Trial registration:ClinicalTrials.gov identifier: NCT03060629. Trial registration:ClinicalTrials.gov identifier: NCT00223080.",

keywords = "Binding antibody multiplex assay, cross-protocol analysis, Env V1V2 binding antibody response breadth score, intracellular cytokine staining, matched polyvalent DNA-polyvalent protein/GLA-SE prime-boost regimen",

author = "Zoe Moodie and Li, {Shuying Sue} and Giorgi, {Elena E.} and Williams, {La Tonya D.} and One Dintwe and Carpp, {Lindsay N.} and Shiyu Chen and Seaton, {Kelly E.} and Sawant, {Sheetal S.} and Lu Zhang and Jack Heptinstall and Shuying Liu and Nicole Grunenberg and Frank Tomaka and Supachai Rerks-Ngarm and Punnee Pitisuttithum and Sorachai Nitayaphan and Ake, {Julie A.} and Sandhya Vasan and Giuseppe Pantaleo and Ian Frank and Baden, {Lindsey R.} and Goepfert, {Paul A.} and Michael Keefer and Mike Chirenje and Hosseinipour, {Mina C.} and Kathryn Mngadi and Fatima Laher and Nigel Garrett and Bekker, {Linda Gail} and {De Rosa}, Stephen and Erica Andersen-Nissen and Kublin, {James G.} and Shan Lu and Gilbert, {Peter B.} and Gray, {Glenda E.} and Lawrence Corey and McElrath, {M. Juliana} and Tomaras, {Georgia D.}",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group, on behalf of Shanghai Shangyixun Cultural Communication Co., Ltd.",

year = "2025",

doi = "10.1080/22221751.2025.2485317",

language = "English",

volume = "14",

journal = "Emerging Microbes and Infections",

issn = "2222-1751",

number = "1",

}

Moodie, Z, Li, SS, Giorgi, EE, Williams, LTD, Dintwe, O, Carpp, LN, Chen, S, Seaton, KE, Sawant, SS, Zhang, L, Heptinstall, J, Liu, S, Grunenberg, N, Tomaka, F, Rerks-Ngarm, S, Pitisuttithum, P, Nitayaphan, S, Ake, JA, Vasan, S, Pantaleo, G, Frank, I, Baden, LR, Goepfert, PA, Keefer, M, Chirenje, M, Hosseinipour, MC, Mngadi, K, Laher, F, Garrett, N, Bekker, LG, De Rosa, S, Andersen-Nissen, E, Kublin, JG, Lu, S, Gilbert, PB, Gray, GE, Corey, L, McElrath, MJ & Tomaras, GD 2025, 'A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials', Emerging Microbes and Infections, vol. 14, no. 1, 2485317. https://doi.org/10.1080/22221751.2025.2485317

A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. / Moodie, Zoe; Li, Shuying Sue; Giorgi, Elena E. et al.
In: Emerging Microbes and Infections, Vol. 14, No. 1, 2485317, 2025.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials

AU - Moodie, Zoe

AU - Li, Shuying Sue

AU - Giorgi, Elena E.

AU - Williams, La Tonya D.

AU - Dintwe, One

AU - Carpp, Lindsay N.

AU - Chen, Shiyu

AU - Seaton, Kelly E.

AU - Sawant, Sheetal S.

AU - Zhang, Lu

AU - Heptinstall, Jack

AU - Liu, Shuying

AU - Grunenberg, Nicole

AU - Tomaka, Frank

AU - Rerks-Ngarm, Supachai

AU - Pitisuttithum, Punnee

AU - Nitayaphan, Sorachai

AU - Ake, Julie A.

AU - Vasan, Sandhya

AU - Pantaleo, Giuseppe

AU - Frank, Ian

AU - Baden, Lindsey R.

AU - Goepfert, Paul A.

AU - Keefer, Michael

AU - Chirenje, Mike

AU - Hosseinipour, Mina C.

AU - Mngadi, Kathryn

AU - Laher, Fatima

AU - Garrett, Nigel

AU - Bekker, Linda Gail

AU - De Rosa, Stephen

AU - Andersen-Nissen, Erica

AU - Kublin, James G.

AU - Lu, Shan

AU - Gilbert, Peter B.

AU - Gray, Glenda E.

AU - Corey, Lawrence

AU - McElrath, M. Juliana

AU - Tomaras, Georgia D.

PY - 2025

Y1 - 2025

N2 - Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints–providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses–two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines. Trial registration:ClinicalTrials.gov identifier: NCT01799954. Trial registration:ClinicalTrials.gov identifier: NCT02109354. Trial registration:ClinicalTrials.gov identifier: NCT02404311. Trial registration:ClinicalTrials.gov identifier: NCT02207920. Trial registration:ClinicalTrials.gov identifier: NCT02296541. Trial registration:ClinicalTrials.gov identifier: NCT03284710. Trial registration:ClinicalTrials.gov identifier: NCT02915016. Trial registration:ClinicalTrials.gov identifier: NCT02997969. Trial registration:ClinicalTrials.gov identifier: NCT03122223. Trial registration:ClinicalTrials.gov identifier: NCT03409276. Trial registration:ClinicalTrials.gov identifier: NCT02968849. Trial registration:ClinicalTrials.gov identifier: NCT03060629. Trial registration:ClinicalTrials.gov identifier: NCT00223080.

AB - Developing an effective HIV vaccine is a momentous challenge. An exceptionally wide range of candidate HIV vaccines have been tested, yet many were poorly immunogenic, and of the select few that advanced into efficacy trials, only one demonstrated any efficacy. Here we report the results of the largest-scale cross-protocol immunogenicity comparison to date: 13 HIV vaccine trials (including 36 vaccine regimens) conducted across nine countries worldwide, strengthened by standardized trial designs, validated assays in centralized laboratories, and harmonized immunogenicity endpoints–providing an objective approach to identify the HIV vaccine candidate(s) with the best immunogenicity. A polyvalent DNA prime + protein boost regimen (HVTN 124) including Env immunogens of four subtypes, matched between prime and boost, achieved the best anti-V1V2 antibody responses by a large margin and also induced high CD4+ T-cell responses–two key immune responses implicated in HIV vaccine protection. Our results provide strong support to test this promising HIV vaccine design in more advanced phase clinical trials and will also guide the future design of additional HIV vaccines. Trial registration:ClinicalTrials.gov identifier: NCT01799954. Trial registration:ClinicalTrials.gov identifier: NCT02109354. Trial registration:ClinicalTrials.gov identifier: NCT02404311. Trial registration:ClinicalTrials.gov identifier: NCT02207920. Trial registration:ClinicalTrials.gov identifier: NCT02296541. Trial registration:ClinicalTrials.gov identifier: NCT03284710. Trial registration:ClinicalTrials.gov identifier: NCT02915016. Trial registration:ClinicalTrials.gov identifier: NCT02997969. Trial registration:ClinicalTrials.gov identifier: NCT03122223. Trial registration:ClinicalTrials.gov identifier: NCT03409276. Trial registration:ClinicalTrials.gov identifier: NCT02968849. Trial registration:ClinicalTrials.gov identifier: NCT03060629. Trial registration:ClinicalTrials.gov identifier: NCT00223080.

KW - Binding antibody multiplex assay

KW - cross-protocol analysis

KW - Env V1V2 binding antibody response breadth score

KW - intracellular cytokine staining

KW - matched polyvalent DNA-polyvalent protein/GLA-SE prime-boost regimen

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U2 - 10.1080/22221751.2025.2485317

DO - 10.1080/22221751.2025.2485317

M3 - Article

AN - SCOPUS:105002219198

SN - 2222-1751

VL - 14

JO - Emerging Microbes and Infections

JF - Emerging Microbes and Infections

IS - 1

M1 - 2485317

ER -