Biology subjects

Coleon, S.

Publications and source records attributed to Coleon, S..

3 recordsLinked to original sources

bioRxiv2026

Rapid vaccine induction of macaque HIV-1 V2 Apex broadly neutralizing antibodies with immunogenetic signatures that are potentially translatable to humans

Due to the complex biology of HIV-1 broadly neutralizing antibodies (bnAbs), HIV-1 vaccines must target unmutated germline precursor antibodies with B cell receptors that have the appropriate specificity and genetic features to develop neutralization breadth. Previous work has shown that immunization or infection in macaques primes unmutated precursor antibodies that target the broadly neutralizing epitope composed of the second variable region and proximal glycans (termed V2-apex site) of HIV-1 envelope (Env). Macaque V2-apex bnAb precursors elicited thus far have homogeneous usage of the second reading frame of a diversity (D) gene found only in macaques, calling into question whether HIV-1 Env immunogens can elicit only this canonical, macaque-specific V2-apex antibody response, limiting human vaccination success. Here, we show that vaccination of rhesus macaques with Env conjugated to a ferritin nanoparticle (OPT4-scNP) rapidly elicited V2-apex bnAbs with distinct D gene segment usage and motifs that are not restricted only to macaques. After two priming immunizations, V2-apex antibodies with non-canonical HCDR3s exhibited greater neutralization potency and breadth than V2-apex antibodies with previously observed HCDR3 motifs. Following sequential boosting immunizations, a V2-apex bnAb lineage with a novel HCDR3-encoded EDGED motif increased its neutralization breadth, including neutralization of viral isolates bearing the N130 glycan, which shields the V2-apex from recognition. High-resolution structures of two members of this V2-apex bnAb lineage, called DH2050, defined a novel binding mode in which it used its EDGED motif to contact the C-strand peptide and the N160 glycan within the V2-apex site. Altogether, we define a novel bnAb binding mode to the V2 Apex and demonstrate that HIV-1 Env sequential vaccination elicits V2-apex bnAbs with immunogenetic signatures that are potentially translatable to the human immune system.

immunology↗

bioRxiv2021

Design, immunogenicity, and efficacy of a pan-sarbecovirus dendritic-cell targeting vaccine

The emergence of SARS-CoV-2 variants of concern (VOCs) that escape pre-existing antibody neutralizing responses increases the need for vaccines that target conserved epitopes and induce cross-reactive B- and T-cell responses. We used a computational approach and sequence alignment analysis to design a new-generation subunit vaccine targeting conserved sarbecovirus B- and T-cell epitopes from Spike (S) and Nucleocapsid (N) to antigen-presenting cells expressing CD40 (CD40.CoV2). We demonstrate the potency of CD40.CoV2 to elicit high levels of cross-neutralizing antibodies against SARS-CoV-2, VOCs, and SARS-CoV-1 in K18-hACE2 transgenic mice, associated with improved viral control and survival after challenge. In addition, we demonstrate the potency of CD40.CoV2 in vitro to recall human multi-epitope, functional, and cytotoxic SARS-CoV-2 S- and N-specific T-cell responses that are unaffected by VOC mutations and cross-reactive with SARS-CoV-1 and, to a lesser extent, MERS epitopes. Overall, these findings provide a framework for a pan-sarbecovirus vaccine.

immunology↗

bioRxiv2018

Antiviral Response by Plasmacytoid Dendritic Cells via Interferogenic Synapse with Infected Cells

Type I interferon (IFN-I) is critical for protection against viral infections. Plasmacytoid dendritic cells (pDCs) massively produce IFN-I against viruses. Physical contacts are required for pDC-mediated sensing of cells infected by genetically distant viruses. How and why these contacts are established remains enigmatic. Using dengue, hepatitis C, zika viruses, we demonstrate that the pDC/infected cell interface is a specialized platform for viral immunostimulatory-RNA transfer, which we named interferogenic synapse and required for pDC-mediated antiviral response. This synapse is an exquisitely differentiated territory with polarized adhesion complexes and regulators of actin network and endocytosis. Toll-like receptor 7-induced signaling in pDCs promotes the interferogenic synapse establishment, thus providing a feed-forward regulation that sustains contacts with infected cells. We propose that the interferogenic synapse is crucial to pDC function as it allows scanning of infected cells to locally secrete IFN-I at the infection site, thereby confining a response potentially deleterious to the host.\n\nHighlightsO_LIpDCs adhere to infected cells via L{beta}2 integrin/ICAM-1\nC_LIO_LIRegulators of actin network and endocytosis polarize at contact\nC_LIO_LITLR7-induced signaling potentiates pDC polarity\nC_LIO_LIInfected cells activate pDCs by interferogenic synapse\nC_LI

microbiology↗