Scholars@Duke
Kshitij G. Wagh

Kshitij G. Wagh

Instructor in the Department of Medicine
Duke Human Vaccine Institute

Selected Publications

Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development.

Journal Article Cell Host Microbe · February 12, 2025 Identifying HIV-1 envelope (Env) traits associated with neutralization cross-reactivity is crucial for vaccine design. Variable loops 1 and 2 (V1V2), positioned at the Env trimer apex, are key regions linked to neutralization. We describe non-canonical cys ... Full text Link to item Cite

Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: a phase 1/2a trial.

Journal Article Nat Med · December 2024 Human immunodeficiency virus type 1 (HIV-1)-specific broadly neutralizing monoclonal antibodies (bNAbs) have to date shown transient viral suppression when administered as monotherapy or as a cocktail of two antibodies1-4. A combination of three bNAbs prov ... Full text Link to item Cite

Neonatal immunity associated with heterologous HIV-1 neutralizing antibody induction in SHIV-infected Rhesus Macaques.

Journal Article Nat Commun · November 27, 2024 The details of the pediatric immune system that supports induction of antibodies capable of neutralizing geographically-diverse or heterologous HIV-1 is currently unclear. Here we explore the pediatric immune environment in neonatal macaque undergoing Simi ... Full text Link to item Cite

Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.

Journal Article Nat Commun · November 3, 2024 Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and-error search for ... Full text Link to item Cite

Viral Envelope Evolution in Simian-HIV-Infected Neonate and Adult-Dam Pairs of Rhesus Macaques.

Journal Article Viruses · June 25, 2024 We recently demonstrated that Simian-HIV (SHIV)-infected neonate rhesus macaques (RMs) generated heterologous HIV-1 neutralizing antibodies (NAbs) with broadly-NAb (bNAb) characteristics at a higher frequency compared with their corresponding dam. Here, we ... Full text Link to item Cite

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans.

Journal Article Cell · June 6, 2024 A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposom ... Full text Link to item Cite

HIResist: a database of HIV-1 resistance to broadly neutralizing antibodies.

Journal Article Bioinformatics · March 4, 2024 MOTIVATION: Changing the course of the human immunodeficiency virus type I (HIV-1) pandemic is a high public health priority with approximately 39 million people currently living with HIV-1 (PLWH) and about 1.5 million new infections annually worldwide. Br ... Full text Link to item Cite

Neutralization escape by SARS-CoV-2 Omicron subvariant BA.2.86.

Journal Article Vaccine · November 13, 2023 The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant BA.2.86 has over 30 mutations in spike compared with BA.2 and XBB.1.5, which raised the possibility that BA.2.86 might evade neutralizing antibodies (NAbs) induced by vaccination or i ... Full text Link to item Cite

Divide and conquer: broadly neutralizing antibody combinations for improved HIV-1 viral coverage.

Journal Article Curr Opin HIV AIDS · July 1, 2023 PURPOSE OF REVIEW: Successful HIV-1 prevention and therapy will require broad and potent coverage of within-host and global viral diversity. Broadly neutralizing antibody (bNAb) combination and multispecific therapeutics provide an opportunity to meet this ... Full text Link to item Cite

Structural basis for breadth development in the HIV-1 V3-glycan targeting DH270 antibody clonal lineage.

Journal Article Nat Commun · May 15, 2023 Antibody affinity maturation enables adaptive immune responses to a wide range of pathogens. In some individuals broadly neutralizing antibodies develop to recognize rapidly mutating pathogens with extensive sequence diversity. Vaccine design for pathogens ... Full text Link to item Cite

SARS-CoV-2 variant transition dynamics are associated with vaccination rates, number of co-circulating variants, and convalescent immunity.

Journal Article EBioMedicine · May 2023 BACKGROUND: Throughout the COVID-19 pandemic, the SARS-CoV-2 virus has continued to evolve, with new variants outcompeting existing variants and often leading to different dynamics of disease spread. METHODS: In this paper, we performed a retrospective ana ... Full text Link to item Cite

Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies.

Journal Article Nat Rev Immunol · March 2023 After nearly four decades of research, a safe and effective HIV-1 vaccine remains elusive. There are many reasons why the development of a potent and durable HIV-1 vaccine is challenging, including the extraordinary genetic diversity of HIV-1 and its compl ... Full text Link to item Cite

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies.

Journal Article mBio · February 28, 2023 HIV-1 and its SIV precursors share a broadly neutralizing antibody (bNAb) epitope in variable loop 2 (V2) at the envelope glycoprotein (Env) trimer apex. Here, we tested the immunogenicity of germ line-targeting versions of a chimpanzee SIV (SIVcpz) Env in ... Full text Link to item Cite

Immunogenicity and protective efficacy of a rhesus adenoviral vaccine targeting conserved COVID-19 replication transcription complex

Journal Article npj Vaccines · December 1, 2022 The COVID-19 pandemic marks the third coronavirus pandemic this century (SARS-CoV-1, MERS, SARS-CoV-2), emphasizing the need to identify and evaluate conserved immunogens for a pan-sarbecovirus vaccine. Here we investigate the potential utility of a T-cell ... Full text Cite

Safety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial.

Journal Article Nat Med · June 2022 HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a two-part study consisting of a single-center, r ... Full text Link to item Cite

mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.

Journal Article Cell Rep · March 15, 2022 The success of nucleoside-modified mRNAs in lipid nanoparticles (mRNA-LNP) as COVID-19 vaccines heralded a new era of vaccine development. For HIV-1, multivalent envelope (Env) trimer protein nanoparticles are superior immunogens compared with trimers alon ... Full text Link to item Cite

Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial.

Journal Article Nat Med · October 2021 Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial ... Full text Link to item Cite

Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens.

Journal Article PLoS Pathog · October 2021 HIV-1 vaccine immunofocusing strategies may be able to induce broadly-reactive neutralizing antibodies (NAbs). Here, we engineered a panel of diverse, membrane-resident native HIV-1 trimers vulnerable to two broad targets-the V2 apex and fusion peptide (FP ... Full text Link to item Cite

Development of Martini 2.2 parameters for N-glycans: a case study of the HIV-1 Env glycoprotein dynamics.

Journal Article Glycobiology · August 7, 2021 N-linked glycans are ubiquitous in nature and play key roles in biology. For example, glycosylation of pathogenic proteins is a common immune evasive mechanism, hampering the development of successful vaccines. Due to their chemical variability and complex ... Full text Link to item Cite

Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates.

Journal Article PLoS Pathog · June 2021 A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccinati ... Full text Link to item Cite

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines.

Journal Article Cell Host Microbe · April 14, 2021 All current vaccines for COVID-19 utilize ancestral SARS-CoV-2 spike with the goal of generating protective neutralizing antibodies. The recent emergence and rapid spread of several SARS-CoV-2 variants carrying multiple spike mutations raise concerns about ... Full text Link to item Cite

Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.

Journal Article Science · January 8, 2021 Neutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency virus ... Full text Open Access Link to item Cite

Combinations of Single Chain Variable Fragments From HIV Broadly Neutralizing Antibodies Demonstrate High Potency and Breadth.

Journal Article Front Immunol · 2021 Broadly neutralizing antibodies (bNAbs) are currently being assessed in clinical trials for their ability to prevent HIV infection. Single chain variable fragments (scFv) of bNAbs have advantages over full antibodies as their smaller size permits improved ... Full text Link to item Cite

Hitting the sweet spot: exploiting HIV-1 glycan shield for induction of broadly neutralizing antibodies.

Journal Article Curr Opin HIV AIDS · September 2020 PURPOSE OF REVIEW: The surface of the HIV-1 Env glycoprotein, the target of neutralizing antibodies, is extensively covered by N-linked glycans that create a glycan shield. Broadly neutralizing antibodies (bNAbs), the primary targets of HIV-1 vaccine desig ... Full text Link to item Cite

Vaccines and Broadly Neutralizing Antibodies for HIV-1 Prevention.

Journal Article Annu Rev Immunol · April 26, 2020 Development of improved approaches for HIV-1 prevention will likely be required for a durable end to the global AIDS pandemic. Recent advances in preclinical studies and early phase clinical trials offer renewed promise for immunologic strategies for block ... Full text Link to item Cite

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Journal Article Cell Host Microbe · January 9, 2019 Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large vir ... Full text Link to item Cite

Completeness of HIV-1 Envelope Glycan Shield at Transmission Determines Neutralization Breadth.

Journal Article Cell Rep · October 23, 2018 Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interp ... Full text Link to item Cite

Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines Features that Contribute to Protection.

Journal Article Cell · August 9, 2018 Antibodies are promising post-exposure therapies against emerging viruses, but which antibody features and in vitro assays best forecast protection are unclear. Our international consortium systematically evaluated antibodies against Ebola virus (EBOV) usi ... Full text Link to item Cite

Potential of conventional & bispecific broadly neutralizing antibodies for prevention of HIV-1 subtype A, C & D infections.

Journal Article PLoS Pathog · March 2018 There is great interest in passive transfer of broadly neutralizing antibodies (bnAbs) and engineered bispecific antibodies (Abs) for prevention of HIV-1 infections due to their in vitro neutralization breadth and potency against global isolates and long i ... Full text Link to item Cite

Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody.

Journal Article Cell Rep · February 13, 2018 Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for i ... Full text Link to item Cite

A single, continuous metric to define tiered serum neutralization potency against HIV.

Journal Article Elife · January 19, 2018 HIV-1 Envelope (Env) variants are grouped into tiers by their neutralization-sensitivity phenotype. This helped to recognize that tier 1 neutralization responses can be elicited readily, but do not protect against new infections. Tier 3 viruses are the lea ... Full text Link to item Cite

Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail.

Journal Article Sci Transl Med · September 20, 2017 HIV-1 sequence diversity presents a major challenge for the clinical development of broadly neutralizing antibodies (bNAbs) for both therapy and prevention. Sequence variation in critical bNAb epitopes has been observed in most HIV-1-infected individuals a ... Full text Link to item Cite

Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge.

Journal Article Sci Transl Med · September 6, 2017 Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, ha ... Full text Link to item Cite

Correction: Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization.

Journal Article PLoS Pathog · September 2017 [This corrects the article DOI: 10.1371/journal.ppat.1005742.]. ... Full text Link to item Cite

Antigenicity-defined conformations of an extremely neutralization-resistant HIV-1 envelope spike.

Journal Article Proc Natl Acad Sci U S A · April 25, 2017 The extraordinary genetic diversity of the HIV-1 envelope spike [Env; trimeric (gp160)3, cleaved to (gp120/gp41)3] poses challenges for vaccine development. Envs of different clinical isolates exhibit different sensitivities to antibody-mediated neutraliza ... Full text Link to item Cite

Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies.

Journal Article Sci Transl Med · March 15, 2017 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 successful in indu ... Full text Link to item Cite

Histidine 375 Modulates CD4 Binding in HIV-1 CRF01_AE Envelope Glycoproteins.

Journal Article J Virol · February 15, 2017 UNLABELLED: The envelope glycoproteins (Envs) from human immunodeficiency virus type 1 (HIV-1) mediate viral entry. The binding of the HIV-1 gp120 glycoprotein to CD4 triggers conformational changes in gp120 that allow high-affinity binding to its corecept ... Full text Link to item Cite

Potent and broad HIV-neutralizing antibodies in memory B cells and plasma.

Journal Article Sci Immunol · January 27, 2017 Induction of broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development. Antibody 10E8, reactive with the distal portion of the membrane-proximal external region (MPER) of HIV-1 gp41, is broadly neutralizing. However, the ontogeny of di ... Full text Link to item Cite

Polyvalent vaccine approaches to combat HIV-1 diversity.

Journal Article Immunol Rev · January 2017 A key unresolved challenge for developing an effective HIV-1 vaccine is the discovery of strategies to elicit immune responses that are able to cross-protect against a significant fraction of the diverse viruses that are circulating worldwide. Here, we sum ... Full text Link to item Cite

Features of Recently Transmitted HIV-1 Clade C Viruses that Impact Antibody Recognition: Implications for Active and Passive Immunization.

Journal Article PLoS Pathog · July 2016 The development of biomedical interventions to reduce acquisition of HIV-1 infection remains a global priority, however their potential effectiveness is challenged by very high HIV-1 envelope diversity. Two large prophylactic trials in high incidence, clad ... Full text Link to item Cite

Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G.

Journal Article Cell · May 5, 2016 The HIV-1-envelope (Env) trimer is covered by a glycan shield of ∼90 N-linked oligosaccharides, which comprises roughly half its mass and is a key component of HIV evasion from humoral immunity. To understand how antibodies can overcome the barriers impose ... Full text Link to item Cite

Optimal Combinations of Broadly Neutralizing Antibodies for Prevention and Treatment of HIV-1 Clade C Infection.

Journal Article PLoS Pathog · March 2016 The identification of a new generation of potent broadly neutralizing HIV-1 antibodies (bnAbs) has generated substantial interest in their potential use for the prevention and/or treatment of HIV-1 infection. While combinations of bnAbs targeting distinct ... Full text Link to item Cite

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants.

Journal Article Viruses · October 21, 2015 Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that gener ... Full text Link to item Cite

Improving neutralization potency and breadth by combining broadly reactive HIV-1 antibodies targeting major neutralization epitopes.

Journal Article J Virol · March 2015 UNLABELLED: The isolation of broadly neutralizing HIV-1 monoclonal antibodies (MAbs) to distinct epitopes on the viral envelope glycoprotein (Env) provides the potential to use combinations of MAbs for prevention and treatment of HIV-1 infection. Since man ... Full text Link to item Cite

Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

Journal Article J Virol · February 2015 UNLABELLED: Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses ... Full text Link to item Cite

Bird to human transmission biases and vaccine escape mutants in H5N1 infections.

Journal Article PLoS One · 2014 BACKGROUND: The avian influenza A H5N1 virus occasionally infects humans, with high mortality rates. Although all current human infections are from avian-to-human transmission, it has been shown that H5N1 can be evolved to transmit between mammals, and is ... Full text Link to item Cite

Lactase persistence and lipid pathway selection in the Maasai.

Journal Article PLoS One · 2012 The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseas ... Full text Link to item Cite

The link between integrability, level crossings and exact solution in quantum models

Journal Article Journal of Physics A: Mathematical and Theoretical · April 20, 2009 We investigate the connection between energy level crossings in integrable systems and their integrability, i.e. the existence of a set of non-trivial integrals of motion. In particular, we consider a general quantum Hamiltonian linear in the coupling u, H ... Full text Cite

Top production at the Tevatron/LHC and nonstandard, strongly interacting spin one particles

Journal Article Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics · November 29, 2007 In this Letter, we consider possible constraints from t over(t, ̄) production on the gauge bosons of theories with an extended strong interaction sector such as axigluons or flavour universal colorons. Such constraints are found to be competitive with those ... Full text Cite

Equilibration problem for the generalized Langevin equation

Journal Article EPL · September 1, 2007 We consider the problem of equilibration of a single-oscillator system with dynamics given by the generalized classical Langevin equation. It is well known that this dynamics can be obtained if one considers a model where the single oscillator is coupled t ... Full text Cite