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Vaccination induces maturation in a mouse model of diverse unmutated VRC01-class precursors to HIV-neutralizing antibodies with >50% breadth

Immunity. 2021-01; 
Xuejun Chen, Tongqing Zhou, Stephen D Schmidt, Hongying Duan, Cheng Cheng, Gwo-Yu Chuang, Ying Gu, Mark K Louder, Bob C Lin, Chen-Hsiang Shen, Zizhang Sheng, Michelle X Zheng, Nicole A Doria-Rose, M Gordon Joyce, Lawrence Shapiro, Ming Tian, Frederick W Alt, Peter D Kwong, John R Mascola
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PCR Cloning and Subcloning … The confirmed heavy or light chain sequences containing the whole V(D) J or VJ segments were synthesized by GenScript and cloned into a mouse IgG2a (VRC2742) or mouse Kappa (… Get A Quote

摘要

Vaccine elicitation of broadly neutralizing antibodies (bnAbs) is a key HIV-research goal. The VRC01 class of bnAbs targets the CD4-binding site on the HIV-envelope trimer and requires extensive somatic hypermutation (SHM) to neutralize effectively. Despite substantial progress, vaccine-induced VRC01-class antibodies starting from unmutated precursors have exhibited limited neutralization breadth, particularly against viruses bearing glycan on loop D residue N276 (glycan276), present on most circulating strains. Here, using sequential immunization of immunoglobulin (Ig)-humanized mice expressing diverse unmutated VRC01-class antibody precursors, we elicited serum responses capable of neutralizing viruses bearin... More

关键词

HIV-1 vaccine, antibody VRC01, broadly neutralizing antibody, glyan276, somatic hypermutation