National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
A1144462
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM129547
米国
引用
ジャーナル: Science / 年: 2024 タイトル: mRNA-LNP HIV-1 trimer boosters elicit precursors to broad neutralizing antibodies. 著者: 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 / ...著者: 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 / 要旨: 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.
名称: HIV Env germline targeting BG505_MD64_N332-GT5 SOSIP in complex with V3-glycan polyclonal Fab isolated from immunized BG18HCgl knock-in mice V3-glycan epitope polyclonal Fab heavy chain タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES
分子量
実験値: NO
由来(天然)
生物種: Mus musculus (ハツカネズミ)
緩衝液
pH: 7.4
試料
濃度: 2.6 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES
試料支持
グリッドの材料: GOLD / グリッドのタイプ: UltrAuFoil R1.2/1.3
急速凍結
装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K