Krisha McKee
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View article: Yeast Display Reveals Plentiful Mutations That Improve Fusion Peptide Vaccine-Elicited Antibodies Beyond 59% HIV-1 Neutralization Breadth
Yeast Display Reveals Plentiful Mutations That Improve Fusion Peptide Vaccine-Elicited Antibodies Beyond 59% HIV-1 Neutralization Breadth Open
Background/Objectives: Vaccine elicitation of antibodies with high HIV-1 neutralization breadth is a long-standing goal. Recently, the induction of such antibodies has been achieved at the fusion peptide site of vulnerability. Questions re…
View article: Vaccine Elicitation of HIV-1 Neutralizing Antibodies Against Both V2 Apex and Fusion Peptide in Rhesus Macaques
Vaccine Elicitation of HIV-1 Neutralizing Antibodies Against Both V2 Apex and Fusion Peptide in Rhesus Macaques Open
SUMMARY Broadly neutralizing antibodies targeting multiple sites of HIV-1 Env vulnerability can be induced by infection, but simultaneous elicitation of neutralizing antibodies (NAbs) against multiple epitopes has not yet been achieved by …
View article: Yeast Display Reveals Plentiful Mutations that Improve Fusion-Peptide Vaccine-Elicited Antibodies Beyond 59% HIV-1-Neutralization Breadth
Yeast Display Reveals Plentiful Mutations that Improve Fusion-Peptide Vaccine-Elicited Antibodies Beyond 59% HIV-1-Neutralization Breadth Open
Background/Objectives: Vaccine elicitation of antibodies with high HIV-1-neutralization breadth is a long-standing goal. Recently, induction of such antibodies has been achieved at the fusion peptide-site of vulnerability; questions remain…
View article: BRAVE: a highly accurate method for predicting HIV-1 antibody resistance using large language models for proteins
BRAVE: a highly accurate method for predicting HIV-1 antibody resistance using large language models for proteins Open
Motivation Broadly neutralizing antibodies (bNAbs) that target the envelope glycoprotein (Env) of human immunodeficiency virus-1 (HIV-1) have been utilized in clinical trials aimed at preventing and treating HIV-1 infections. However, the …
View article: Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage
Structural development of the HIV-1 apex-directed PGT145-PGDM1400 antibody lineage Open
View article: Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains Open
View article: Ultrapotent Broadly Neutralizing Human‐llama Bispecific Antibodies against HIV‐1
Ultrapotent Broadly Neutralizing Human‐llama Bispecific Antibodies against HIV‐1 Open
Broadly neutralizing antibodies are proposed as therapeutic and prophylactic agents against HIV‐1, but their potency and breadth are less than optimal. This study describes the immunization of a llama with the prefusion‐stabilized HIV‐1 en…
View article: An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals
An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals Open
Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in mo…
View article: Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site
Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site Open
The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.0…
View article: Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases
Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases Open
Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these trimers from their native membrane-bound context. To assess whether glycosylation could limit these …
View article: Improved HIV-1 neutralization breadth and potency of V2-apex antibodies by in silico design
Improved HIV-1 neutralization breadth and potency of V2-apex antibodies by in silico design Open
Broadly neutralizing antibodies (bNAbs) against HIV can reduce viral transmission in humans, but an effective therapeutic will require unusually high breadth and potency of neutralization. We employ the OSPREY computational protein design …
View article: Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections
Trispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections Open
View article: Improved pharmacokinetics of HIV-neutralizing VRC01-class antibodies achieved by reduction of net positive charge on variable domain
Improved pharmacokinetics of HIV-neutralizing VRC01-class antibodies achieved by reduction of net positive charge on variable domain Open
The amino-acid composition of the immunoglobulin variable region has been observed to impact antibody pharmacokinetics (PK). Here, we sought to improve the PK of the broad HIV-1-neutralizing VRC01-class antibodies, VRC07-523LS and N6LS, by…
View article: Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization
Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization Open
The HIV-1 fusion peptide has been identified as a site for elicitation of broadly neutralizing antibodies, with prior studies demonstrating that priming with fusion peptide-based immunogens and boosting with soluble envelope (Env) trimers …
View article: Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency
Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency Open
Antibody CAP256-VRC26.25 targets the second hypervariable region (V2) at the apex of the HIV envelope (Env) trimer with extraordinary neutralization potency, although less than optimal breadth. To improve breadth, we linked the light chain…
View article: Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life
Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life Open
The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, …
View article: Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life
Engineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life Open
The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed several unusual features. First, …
View article: Potent anti-viral activity of a trispecific HIV neutralizing antibody in SHIV-infected monkeys
Potent anti-viral activity of a trispecific HIV neutralizing antibody in SHIV-infected monkeys Open
Broadly neutralizing antibodies (bNAbs) represent an alternative to drug therapy for the treatment of HIV-1 infection. Immunotherapy with single bNAbs often leads to emergence of escape variants, suggesting a potential benefit of combinati…
View article: Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography
Structures of HIV-1 Neutralizing Antibody 10E8 Delineate the Mechanistic Basis of Its Multi-Peak Behavior on Size-Exclusion Chromatography Open
Antibody 10E8 is capable of effectively neutralizing HIV through its recognition of the membrane-proximal external region (MPER), and a suitably optimized version of 10E8 might have utility in HIV therapy and prophylaxis. However, 10E8 dis…
View article: A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention
A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention Open
Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve VRC01-class antibodies, we combined structu…
View article: Potent Anti-Viral Activity of a Trispecific HIV Antibody in SHIV-Infected Monkeys
Potent Anti-Viral Activity of a Trispecific HIV Antibody in SHIV-Infected Monkeys Open
View article: Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors Open
The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated…
View article: Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody
Fc-mediated effector function contributes to the in vivo antiviral effect of an HIV neutralizing antibody Open
Significance Neutralizing antibodies (NAbs) against HIV-1 are under clinical development. Despite demonstrated antiviral activity when used as treatment in HIV-infected people, the mechanism of action of NAbs remains controversial. Quantif…
View article: Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies
Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies Open
A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been s…
View article: Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition
Structure of Super-Potent Antibody CAP256-VRC26.25 in Complex with HIV-1 Envelope Reveals a Combined Mode of Trimer-Apex Recognition Open
Antibodies targeting the V1V2 apex of the HIV-1 envelope (Env) trimer comprise one of the most commonly elicited categories of broadly neutralizing antibodies. Structures of these antibodies indicate diverse modes of Env recognition typifi…
View article: Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen
Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen Open
View article: A Structure-Based Matrix Approach Yields Improved VRC01-Class Antibodies for HIV-1 Therapy and Prevention
A Structure-Based Matrix Approach Yields Improved VRC01-Class Antibodies for HIV-1 Therapy and Prevention Open
View article: Removal of variable domain <i>N</i> -linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies
Removal of variable domain <i>N</i> -linked glycosylation as a means to improve the homogeneity of HIV-1 broadly neutralizing antibodies Open
Broadly neutralizing antibodies are showing promise in the treatment and prevention of HIV-1, with several now being evaluated clinically. Some lead clinical candidates, including antibodies CAP256-VRC26.25, N6, PGT121, and VRC07-523, have…
View article: Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability Open
View article: Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual
Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual Open