A recent study published in Nature Immunology showed that germline-targeting epitope scaffold nanoparticles elicit rare broadly neutralizing antibody (bnAb) precursors against human immunodeficiency virus (HIV). Study: Vaccination induces broadly neutralizing antibody precursors to HIV gp41 . Image Credit: Salov Evgeniy/Shutterstock.
com Broad vaccination protection against antigenically diverse viruses, such as beta coronaviruses, hepatitis C virus, HIV, and influenza virus, requires bnAbs against the conserved epitopes on variable membrane glycoproteins . While monoclonal bnAbs have been identified for these viruses, strategies to elicit bnAbs with predefined binding specificities and genetic features are needed. In germline-targeting vaccine design, the priming immunogen elicits responses from rare bnAb-precursor B cells with the required genetic features for bnAb development.
After priming, sequential boosting with immunogens similar to native glycoproteins can guide B cell maturation to produce bnAbs against the target epitope. This approach has been demonstrated for VRC01 class bnAbs for the HIV envelope CD4-binding site in humans. However, most VRC01-class bnAbs exhibit heavy chain complementarity determining region 3 (HCDR3)-dominant interactions.
HCDR3-dominant bnAbs against the HIV envelop protein’s (Env) membrane-proximal external region (MPER) will be crucial as such bnAbs (e.g., DH511, LN01, and 10E8) have high neutralization breadth.
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