National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI144462
United States
Citation
Journal: Science / Year: 2024 Title: mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies. Authors: Zhenfei Xie / Ying-Cing Lin / Jon M Steichen / Gabriel Ozorowski / Sven Kratochvil / Rashmi Ray / Jonathan L Torres / Alessia Liguori / Oleksandr Kalyuzhniy / Xuesong Wang / John E Warner / ...Authors: Zhenfei Xie / Ying-Cing Lin / Jon M Steichen / Gabriel Ozorowski / Sven Kratochvil / Rashmi Ray / Jonathan L Torres / Alessia Liguori / Oleksandr Kalyuzhniy / Xuesong Wang / John E Warner / Stephanie R Weldon / Gordon A Dale / Kathrin H Kirsch / Usha Nair / Sabyasachi Baboo / Erik Georgeson / Yumiko Adachi / Michael Kubitz / Abigail M Jackson / Sara T Richey / Reid M Volk / Jeong Hyun Lee / Jolene K Diedrich / Thavaleak Prum / Samantha Falcone / Sunny Himansu / Andrea Carfi / John R Yates / James C Paulson / Devin Sok / Andrew B Ward / William R Schief / Facundo D Batista / Abstract: Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells ...Germline-targeting (GT) HIV vaccine strategies are predicated on deriving broadly neutralizing antibodies (bnAbs) through multiple boost immunogens. However, as the recruitment of memory B cells (MBCs) to germinal centers (GCs) is inefficient and may be derailed by serum antibody-induced epitope masking, driving further B cell receptor (BCR) modification in GC-experienced B cells after boosting poses a challenge. Using humanized immunoglobulin knockin mice, we found that GT protein trimer immunogen N332-GT5 could prime inferred-germline precursors to the V3-glycan-targeted bnAb BG18 and that B cells primed by N332-GT5 were effectively boosted by either of two novel protein immunogens designed to have minimum cross-reactivity with the off-target V1-binding responses. The delivery of the prime and boost immunogens as messenger RNA lipid nanoparticles (mRNA-LNPs) generated long-lasting GCs, somatic hypermutation, and affinity maturation and may be an effective tool in HIV vaccine development.
Entire : N332-GT5 SOSIP in complex with base polyclonal Fabs isolated at d...
Entire
Name: N332-GT5 SOSIP in complex with base polyclonal Fabs isolated at day 42 from protein immunized BG18HCgl knock-in mice
Components
Complex: N332-GT5 SOSIP in complex with base polyclonal Fabs isolated at day 42 from protein immunized BG18HCgl knock-in mice
Complex: Base polyclonal Fabs
Complex: N332-GT5 SOSIP
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Supramolecule #1: N332-GT5 SOSIP in complex with base polyclonal Fabs isolated at d...
Supramolecule
Name: N332-GT5 SOSIP in complex with base polyclonal Fabs isolated at day 42 from protein immunized BG18HCgl knock-in mice type: complex / ID: 1 / Parent: 0
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