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Heavy-chain CDR3-engineered B cells facilitate in vivo evaluation of HIV-1 vaccine candidates.
He, Wenhui; Ou, Tianling; Skamangas, Nickolas; Bailey, Charles C; Bronkema, Naomi; Guo, Yan; Yin, Yiming; Kobzarenko, Valerie; Zhang, Xia; Pan, Andi; Liu, Xin; Xu, Jinge; Zhang, Lizhou; Allwardt, Ava E; Mitra, Debasis; Quinlan, Brian; Sanders, Rogier W; Choe, Hyeryun; Farzan, Michael.
Afiliação
  • He W; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Immu
  • Ou T; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Immu
  • Skamangas N; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.
  • Bailey CC; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.
  • Bronkema N; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Skaggs Graduate School, Scripps Research, La Jolla, CA 92037, USA.
  • Guo Y; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.
  • Yin Y; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Kobzarenko V; Department of Computer Engineering and Sciences, Florida Institute of Technology, Melbourne, FL 32901, USA.
  • Zhang X; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.
  • Pan A; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Skaggs Graduate School, Scripps Research, La Jolla, CA 92037, USA.
  • Liu X; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Xu J; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Zhang L; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.
  • Allwardt AE; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Mitra D; Department of Computer Engineering and Sciences, Florida Institute of Technology, Melbourne, FL 32901, USA.
  • Quinlan B; Department of Immunology and Microbiology, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.
  • Sanders RW; Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
  • Choe H; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
  • Farzan M; Division of Infectious Disease, Boston Children's Hospital, Boston, MA 02115, USA; The Center for Integrated Solutions to Infectious Diseases, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Skaggs Graduate Sc
Immunity ; 56(10): 2408-2424.e6, 2023 10 10.
Article em En | MEDLINE | ID: mdl-37531955
V2-glycan/apex broadly neutralizing antibodies (bnAbs) recognize a closed quaternary epitope of the HIV-1 envelope glycoprotein (Env). This closed structure is necessary to elicit apex antibodies and useful to guide the maturation of other bnAb classes. To compare antigens designed to maintain this conformation, we evaluated apex-specific responses in mice engrafted with a diverse repertoire of B cells expressing the HCDR3 of the apex bnAb VRC26.25. Engineered B cells affinity matured, guiding the improvement of VRC26.25 itself. We found that soluble Env (SOSIP) variants differed significantly in their ability to raise anti-apex responses. A transmembrane SOSIP (SOSIP-TM) delivered as an mRNA-lipid nanoparticle elicited more potent neutralizing responses than multimerized SOSIP proteins. Importantly, SOSIP-TM elicited neutralizing sera from B cells engineered with the predicted VRC26.25-HCDR3 progenitor, which also affinity matured. Our data show that HCDR3-edited B cells facilitate efficient in vivo comparisons of Env antigens and highlight the potential of an HCDR3-focused vaccine approach.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas / Infecções por HIV / HIV-1 / Vacinas contra a AIDS Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas / Infecções por HIV / HIV-1 / Vacinas contra a AIDS Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article