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[Preprint]. 2024 Apr 8:rs.3.rs-3895128.

doi: 10.21203/rs.3.rs-3895128/v1.

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens

Jenna M DeLuca¹, Maria Blasi^{2

3}, Shalini Jha^{2

4}, Xiaoying Shen^{2

4}, Justin Pollara^{2

4}, Melissa Kerkau^{2

4}, Mansi Purwar⁵, Diane G Carnathan⁶, Donatella Negri^{2

3

7}, Andrea Cara^{2

3

8}, Kurt Wollenberg⁹, Kevin O Saunders^{2

4}, Shan Lu¹⁰, Guido Silvestri⁶, David B Weiner⁵, Mary E Klotman^{2

3}, Guido Ferrari^{2

4}, M Anthony Moody^{2

11}, Mattia Bonsignori¹

Affiliations

¹ Translational Immunobiology Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
² Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
³ Department of Medicine, Duke University, Durham, NC, USA.
⁴ Department of Surgery, Duke University, Durham, NC, USA.
⁵ Wistar Institute, Philadelphia, PA, USA.
⁶ Emory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
⁷ Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
⁸ National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
⁹ Bioinformatics & Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁰ University of Massachusetts Medical School, Worcester, MA, USA.
¹¹ Department of Pediatrics, Duke University, Durham, NC, USA.

PMID: 38659814
PMCID: PMC11042408
DOI: 10.21203/rs.3.rs-3895128/v1

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens

Jenna M DeLuca et al. Res Sq. 2024.

[Preprint]. 2024 Apr 8:rs.3.rs-3895128.

doi: 10.21203/rs.3.rs-3895128/v1.

Authors

Affiliations

¹ Translational Immunobiology Unit, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
² Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
³ Department of Medicine, Duke University, Durham, NC, USA.
⁴ Department of Surgery, Duke University, Durham, NC, USA.
⁵ Wistar Institute, Philadelphia, PA, USA.
⁶ Emory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
⁷ Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
⁸ National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.
⁹ Bioinformatics & Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
¹⁰ University of Massachusetts Medical School, Worcester, MA, USA.
¹¹ Department of Pediatrics, Duke University, Durham, NC, USA.

PMID: 38659814
PMCID: PMC11042408
DOI: 10.21203/rs.3.rs-3895128/v1

Update in

Convergence and divergence of B cell responses in two HIV-1 Env immunizations in Rhesus macaques.
DeLuca JM, Blasi M, McGee TJ, Jha S, Shen X, Gu S, Pollara J, Kerkau M, Purwar M, Carnathan DG, Negri D, Cara A, Wollenberg K, Wiehe K, Saunders KO, Lu S, Silvestri G, Weiner DB, Klotman ME, Ferrari G, Anthony Moody M, Bonsignori M. DeLuca JM, et al. Commun Med (Lond). 2025 May 15;5(1):175. doi: 10.1038/s43856-025-00899-3. Commun Med (Lond). 2025. PMID: 40374902 Free PMC article.

Abstract

Diverse and rapidly mutating viruses pose challenges to immunogen and vaccine design. In this study, we evaluated the ability of memory B-cells obtained from two independent NHP trials to cross-react with individual HIV-1 vaccine components of two different multivalent immunization strategies. We demonstrated that while an HIV-1 Env multiclade, multivalent immunization regimen resulted in a dominant memory B-cell response that converged toward shared epitopes, in a sequential immunization with clonally-related non-stabilized gp140 HIV-1 Envs followed by SOSIP-stabilized gp140 trimers, the change in immunogen format resulted in repriming of the B-cell response.

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Conflict of interest statement

Additional Declarations: There is NO Competing Interest.

Figures

**Figure 1.. Tetravalent gp120 Env immunization.**
a NHP immunization scheme with multivalent HIV-1 gp120 Env cocktails delivered as DNA and monomeric proteins. b Viremia time-course of the four NHPs included in this study post-seroconversion or after the fifteenth challenge for RVv15. c Immunogen binding profiles of 734 B-cells isolated from all four NHPs. Reactivity with individual and multiple gp120 Env immunogens is color coded as indicated. d Binding to individual immunogens of monoreactive B-cells, expressed as percentage of the total number of monoreactive B-cells. Data are shown as aggregate (“All NHPs”) and for each NHP. e Immunogen cross-reactivity of multireactive B-cells, expressed as percentage of the total number of multireactive B-cells, shown as aggregate (“All NHPs”) and for each NHP.

**Figure 2.. Sequential immunization with clonally related Envs.**
a NHP immunization scheme (see methods and ref). **b,c** Cross-reactivity of B-cells isolated **(b)** before and **(c)** after SOSIP trimer immunizations with non-stabilized gp140 Envs immunogens (outer ring) and stabilized CH505.w136 SOSIP trimer (inner ring). Data are shown as aggregate (“All NHPs”) and for each NHP. Number of B-cells analyzed is shown for each chart. Reactivity with one or more non-stabilized gp140 Env immunogens is color coded as indicated. Absence of binding to any of the four non-stabilized gp140 Env immunogens is shown in gray.

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References

1. Bedi R., Bayless N.L. & Glanville J. Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses. Annu Rev Biomed Data Sci 6, 419–441 (2023). - PubMed
1. Hurwitz J.L. & Bonsignori M. Multi-Envelope HIV-1 Vaccine Development: Two Targeted Immune Pathways, One Desired Protective Outcome. Viral Immunol 31, 124–132 (2018). - PMC - PubMed
1. Blasi M. et al. IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells. Commun Biol 1, 134 (2018). - PMC - PubMed
1. Blasi M. et al. Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs. NPJ Vaccines 5, 107 (2020). - PMC - PubMed
1. Cottrell C.A. et al. Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates. PLoS Pathog 16, e1008753 (2020). - PMC - PubMed

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This is a preprint.

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens

Affiliations

B cell immunofocusing and repriming in two HIV-1 Env immunization regimens

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

Figures

References

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