Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.

dc.contributor.author

Nettere, Danielle

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Unnithan, Shakthi

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Rodgers, Nicole

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Nohara, Junsuke

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Cray, Paul

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Berry, Madison

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Jones, Caroline

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Armand, Lawrence

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Li, Shuk Hang

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Berendam, Stella J

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Fouda, Genevieve G

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Cain, Derek W

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Spence, Taylor N

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Granek, Joshua A

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Davenport, Clemontina A

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Edwards, Robert J

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Wiehe, Kevin

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Van Rompay, Koen KA

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Moody, M Anthony

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Permar, Sallie R

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Pollara, Justin

dc.date.accessioned

2023-12-27T13:34:20Z

dc.date.available

2023-12-27T13:34:20Z

dc.date.issued

2023-11

dc.description.abstract

An effective HIV-1 vaccine remains a critical unmet need for ending the AIDS epidemic. Vaccine trials conducted to date have suggested the need to increase the durability and functionality of vaccine-elicited antibodies to improve efficacy. We hypothesized that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T cell help and improve antibody production against HIV-1. To test this, we developed an innovative conjugate vaccine regimen that used a modified vaccinia virus Ankara (MVA) co-expressing HIV-1 envelope (Env) and the hepatitis B virus surface antigen (HBsAg) as a prime, followed by two Env-HBsAg conjugate protein boosts. We compared the immunogenicity of this conjugate regimen to matched HIV-1 Env-only vaccines in two groups of 5 juvenile rhesus macaques previously immunized with hepatitis B vaccines in infancy. We found expansion of both HIV-1 and HBsAg-specific circulating T follicular helper cells and elevated serum levels of CXCL13, a marker for germinal center activity, after boosting with HBsAg-Env conjugate antigens in comparison to Env alone. The conjugate vaccine elicited higher levels of antibodies binding to select HIV Env antigens, but we did not observe significant improvement in antibody functionality, durability, maturation, or B cell clonal expansion. These data suggests that conjugate vaccination can engage both HIV-1 Env and HBsAg specific T cell help and modify antibody responses at early time points, but more research is needed to understand how to leverage this strategy to improve the durability and efficacy of next-generation HIV vaccines.

dc.identifier

10.1038/s41541-023-00775-y

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2059-0105

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2059-0105

dc.identifier.uri

https://hdl.handle.net/10161/29559

dc.language

eng

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Springer Science and Business Media LLC

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NPJ vaccines

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10.1038/s41541-023-00775-y

dc.rights.uri

https://creativecommons.org/licenses/by-nc/4.0

dc.title

Conjugation of HIV-1 envelope to hepatitis B surface antigen alters vaccine responses in rhesus macaques.

dc.type

Journal article

duke.contributor.orcid

Nettere, Danielle|0000-0002-6238-1991

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Unnithan, Shakthi|0000-0002-7863-8712

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Cain, Derek W|0000-0002-5988-6729

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Granek, Joshua A|0000-0003-3908-5016

duke.contributor.orcid

Moody, M Anthony|0000-0002-3890-5855

pubs.begin-page

183

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1

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Duke

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School of Medicine

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Student

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Staff

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Biostatistics & Bioinformatics

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Integrative Immunobiology

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Molecular Genetics and Microbiology

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Medicine

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Pathology

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Pediatrics

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Surgery

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Medicine, Duke Human Vaccine Institute

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Pediatrics, Infectious Diseases

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Surgery, Surgical Sciences

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Duke Human Vaccine Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

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Initiatives

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Duke Science & Society

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Biostatistics & Bioinformatics, Division of Integrative Genomics

pubs.publication-status

Published

pubs.volume

8

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