Parul Agrawal

Diverse germline-targeting HIV Env immunogens select for distinct mutations in the same knock-in mice B cell receptors

Parul Agrawal, Junli Feng, Latha Kallur Siddaramaiah, Arineh Khechaduri et autres

VRC01-class HIV broadly neutralizing antibodies have been isolated from people living with HIV. Their unmutated (germline) forms do not bind Env and do not neutralize HIV. They acquire their broadly neutralizing potentials through the accumulation of specific somatic mutations. Here, we identify …

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Antibody-mediated diversification of primary and secondary humoral immune responses

Dennis J. Schaefer-Babajew, Laurine Binet, Gabriela S. Silva Santos, Chiara Ruprecht et autres

Humoral immune responses are characterized by increasing antibody affinity and diversity over time. Increased affinity is mediated by a combination of immunoglobulin gene somatic mutation and iterative cycles of selection in germinal centers. Less is understood about how diversity increases. Here, we …

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Antibody Mediated Diversification of Primary and Secondary Humoral Immune Responses

Dennis J. Schaefer-Babajew, Laurine Binet, Gabriela S. Silva Santos, Lachlan Paul Deimel et autres

Abstract Humoral immune responses are characterized by increasing antibody affinity and diversity over time. Increased affinity is mediated by a combination of immunoglobulin gene somatic mutation and iterative cycles of selection in germinal centers. Less is understood about how diversity increases. Here …

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Self-amplifying RNA-based activation of HIV-1 broadly neutralizing antibody B cell precursors 2690

Parul Agrawal, Madison M. Means, Karli Hinton, Arineh Khechaduri et autres

Abstract Description Elicitation of broadly HIV neutralizing antibody (Ab) responses requires sequential immunizations with specifically designed HIV Env-derived proteins. Such constructs are presently in pre-clinical and clinical evaluation, but the production of multiple immunogens is costly, and the implementation of prolonged immunization …

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Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies

Parul Agrawal, Arineh Khechaduri, Kelsey R. Salladay, Anna J. MacCamy et autres

Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class …

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Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-class antibodies

Parul Agrawal, Arineh Khechaduri, Kelsey R. Salladay, Anna J. MacCamy et autres

ABSTRACT Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. …

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Short CDRL1 in intermediate VRC01-like mAbs is not sufficient to overcome key glycan barriers on HIV-1 Env

Parul Agrawal, Maria L. Knudsen, Anna J. MacCamy, Nicholas K. Hurlburt et autres

VRC01-class broadly neutralizing antibodies (bnAbs) have been isolated from people with HIV-1, but they have not yet been elicited by vaccination. They are extensively somatically mutated and sometimes accumulate CDRL1 deletions. Such indels may allow VRC01-class antibodies to accommodate the glycans expressed …

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Adjuvants influence the maturation of VRC01-like antibodies during immunization

Maria L. Knudsen, Parul Agrawal, Anna J. MacCamy, K. Rachael Parks et autres

Once naive B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full maturation of VRC01-class antibodies. Here, we examined whether and …

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Adjuvants influence the maturation of VRC01-like antibodies during immunization

Maria L. Knudsen, Parul Agrawal, Anna J. MacCamy, K. Rachael Parks et autres

ABSTRACT Once naïve B cells expressing germline VRC01-class B cell receptors become activated by germline-targeting immunogens, they enter germinal centers and undergo affinity maturation. Booster immunizations with heterologous Envs are required for the full maturation of VRC01-class antibodies. Here, we examined whether …

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HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors

Yu‐Ru Lin, K. Rachael Parks, Connor E. Weidle, Anika S. Naidu et autres

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Overcoming Steric Restrictions of VRC01 HIV-1 Neutralizing Antibodies through Immunization

K. Rachael Parks, Anna J. MacCamy, Josephine J. Trichka, Matthew D. Gray et autres

02 antibody heavy chains paired with rare light chains expressing 5-amino acid-long CDRL3s. They have been isolated from infected subjects but have not yet been elicited by immunization. Env-derived immunogens capable of binding the germline forms of VRC01 B cell receptors on …

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Stoichiometric Analyses of Soluble CD4 to Native-like HIV-1 Envelope by Single-Molecule Fluorescence Spectroscopy

Parul Agrawal, Anthony L. DeVico, James S. Foulke, George K. Lewis et autres

Analyses of HIV-1 envelope (Env) binding to CD4, and the conformational changes the interactions induce, inform the molecular mechanisms and factors governing HIV-1 infection. To address these questions, we used a single-molecule detection (SMD) approach to study the nature of reactions between …

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