Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1

Xu, K.; Acharya, P.; Kong, R.; Cheng, C.; Chuang, G.-Y.; Liu, K.; Louder, M. K.; O Dell, S.; Rawi, R.; Sastry, M.; Shen, C.-H.; Zhang, B.; Zhou, T.; Asokan, M.; Bailer, R. T.; Chambers, M.; Chen, X.; Choi, C. W.; Dandey, V. P.; Doria-Rose, N. A.; Druz, A.; Eng, E. T.; Farney, S. K.; Foulds, K. E.; Geng, H.; Georgiev, I. S.; Gorman, J.; Hill, K. R.; Jafari, A. J.; Kwon, Y. D.; Lai, Y.-T.; Lemmin, T.; McKee, K.; Ohr, T. Y.; Ou, L.; Peng, D.; Rowshan, A. P.; Sheng, Z.; Todd, J.-P.; Tsybovsky, Y.; Viox, E. G.; Wang, Y.; Wei, H.; Yang, Y.; Zhou, A. F.; Chen, R.; Yang, L.; Scorpio, D. G.; McDermott,

doi:10.1101/306282

Home/Archive/bioRxiv

bioRxiv · 10.1101/306282

Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1

View original source ↗Export metadata ↓

Abstract

A central goal of HIV-1-vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion-stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryo-electron microscopy structures of these antibodies revealed fusion peptide-conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses suggesting translatability. The N terminus of the HIV-1-fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

Source connections

Published article ↗

Explore related subjects

immunology Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Xu, K., Acharya, P., Kong, R., Cheng, C., Chuang, G.-Y., Liu, K., Louder, M. K., O Dell, S., Rawi, R., Sastry, M., Shen, C.-H., Zhang, B., Zhou, T., Asokan, M., Bailer, R. T., Chambers, M., Chen, X., Choi, C. W., Dandey, V. P., Doria-Rose, N. A., Druz, A., Eng, E. T., Farney, S. K., Foulds, K. E., Geng, H., Georgiev, I. S., Gorman, J., Hill, K. R., Jafari, A. J., Kwon, Y. D., Lai, Y.-T., Lemmin, T., McKee, K., Ohr, T. Y., Ou, L., Peng, D., Rowshan, A. P., Sheng, Z., Todd, J.-P., Tsybovsky, Y., Viox, E. G., Wang, Y., Wei, H., Yang, Y., Zhou, A. F., Chen, R., Yang, L., Scorpio, D. G., McDermott,. 2018-04-23. Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. https://doi.org/10.1101/306282

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

CD19-CAR T-cell therapy resets the EBV+ autoreactive B cell repertoire in autoimmune disease

Epstein-Barr virus (EBV) reprograms autoreactive B cells into activated antigen-presenting cells that drive pathogenic T- and B-cell responses in autoimmune disease. Using EBV B-cell sequencing (EBV-seq), we profiled EBV+ B cells in patients treated with CD19 chimeric antigen receptor (CAR) T cells (systemic lupus, n=6; idiopathic inflammatory myopathies, n=3; systemic sclerosis, n=3) or rituximab (n=15). CAR T cells, but not rituximab, depleted EBV+ B cells, resetting the repertoire toward a naive state: predominantly IgM+ with minimal somatic hypermutation. Post-rituximab B-cells remained class-switched, hypermutated, and activated. Monoclonal antibodies cloned from EBV+ B cells lost autoreactivity after CAR T cells but not rituximab. Sustained drug-free remission occurred in 8/12 CAR-treated but 0/15 rituximab-treated patients. EBV+ B cells were predominantly Latency III and resisted anti-CD20 and anti-CD19 antibodies, yet were killed by CAR T cells and T-cell engagers. CD19-CAR T-cell therapy resets the autoreactive EBV+ B-cell repertoire, which may underlie sustained drug-free remission.

immunology↗

bioRxiv2026

A minimal two-residue C-terminal truncation of AID in adult-onset hyper-IgM syndrome type 2 (HIGM2)

Activation-induced cytidine deaminase (AID), encoded by AICDA, facilitates class-switch recombination (CSR) and somatic hypermutation (SHM) in activated B cells. Loss of AID function causes hyper-IgM syndrome type 2 (HIGM2). While typically autosomal recessive, three C-terminal truncation variants have been reported to act in autosomal dominant manner. We describe a novel heterozygous AICDA nonsense variant, c.589G>T (p.G197*), that truncates the final two C-terminal residues of AID and results in adult-onset HIGM2. Single-cell sequencing of primary patient B cells revealed a complete block in CSR and a [~]10-fold reduction in SHM. AICDA mRNA expression was balanced between wild-type and variant alleles, yet AID protein abundance was reduced to [~]56% with normal subcellular localization. Remarkably, inducible germinal center (iGB) cultures restored CSR in purified naive patient B cells. CRISPR-Cas9 editing of healthy donor B cells confirmed that the iGB platform can rescue B cells harboring heterozygous, but not homozygous, AICDA variants. These results demonstrate that even a two-amino-acid truncation at the AID C-terminus is sufficient to disrupt its function and cause HIGM2.

immunology↗

bioRxiv2026

Defining the Functional Consequence of the Human Ocular Microbiome

The ocular surface is one of the body's most environmentally exposed mucosal barriers, yet it is considered low biomass and harbors orders of magnitude fewer bacteria than microbe-rich sites like the gut. This has cast doubt on whether a functional core ocular microbiome exists at all. Having previously defined a protective gd T cell and IL-17 axis engaged by the murine commensal Corynebacterium mastitidis, we asked whether human-derived bacteria could do the same. Pairing sequencing and culturomics of healthy human conjunctiva from two geographically distinct cohorts, we define a stable core microbiome and identify Corynebacterium bovis as a consistent eye-resident commensal rather than a transient contaminant. In humans, C. bovis elicits a non-pathogenic response marked by IL-17 secretion by {gamma}{delta} T cells and circulating C. bovis-specific IgG, which suggests commensalism rather than pathology. Colonizing mice with human C. bovis strains from Pittsburgh or Miami reproduced this program and conferred protection against ocular infection with Staphylococcus aureus. Together, these findings identify C. bovis as a human-derived ocular commensal that can drive protective {gamma}{delta} T cell immunity, translating a mechanism previously defined only in mice into human relevance and a rational target against sight-threatening infection.

immunology↗