Preparation of functional IgY that potently neutralizes HIV-1 in TZM-bl Cell line

ABSTRACTAIDS caused by HIV is one of the most serious public health challenges in the world. As we all know, Antiretroviral therapy (ART) is the most effective way to treat AIDS so far, however, forthe reasons of drug resistance, side effects, compliance, economy, limited its using widely. On the other hand, AIDS cannot be completely cured by ART. While the characterization of bnAbs (broadly neutralizing antibodies) in potent HIV neutralization provides considerable insight into HIV curing, it also can be used for passive immunotherapy or combination with ART for HIV-1 treatment. Here we report a novel technology to produce an neutralized activity bnAbs named HIV-1-IgY, which was extracted from the immunized Chicken egg by pNL4-3 virus antigens, and further purified using Water dilution and Salting out method. The specificity, titer and neutralizing activity of HIV-1-IgY was analyzed by Western blotting, ELISA and TZM-bl cell line evaluation system respectively. The results showed that theHIV-1-IgY has high neutralized activity to HIV in vitro; nearly 90% of HIV-1 were neutralized at 1.89μM in TZM-blsystem, which indicated that IgY may be a source of antibodies for AIDS prevention and treatment. Despite its needs to further consider and evaluate neutralized activity in-vivo and the potential mechanisms, Our data showed that we obtained an HIV-1-IgY which could effectively neutralize HIV-l IIIB virus in vitro.

Download Full-text

Expression of HIV-1 broadly neutralizing antibodies mediated by recombinant adeno-associated virus 8 in vitro and in vivo

Molecular Immunology ◽

10.1016/j.molimm.2016.10.011 ◽

2016 ◽

Vol 80 ◽

pp. 68-77

Author(s):

Yongjiao Yu ◽

Lu Fu ◽

Xiaoyu Jiang ◽

Shanshan Guan ◽

Ziyu Kuai ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Broadly Neutralizing Antibodies ◽

Adeno Associated Virus ◽

Hiv 1

Download Full-text

Covalent Linkage of HIV-1 Trimers to Synthetic Liposomes Elicits Improved B Cell and Antibody Responses

Journal of Virology ◽

10.1128/jvi.00443-17 ◽

2017 ◽

Vol 91 (16) ◽

Cited By ~ 31

Author(s):

Shridhar Bale ◽

Geraldine Goebrecht ◽

Armando Stano ◽

Richard Wilson ◽

Takayuki Ota ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Germinal Center ◽

Neutralizing Antibodies ◽

Tier 2 ◽

Covalent Linkage ◽

His Tag ◽

Hiv 1

ABSTRACT We have demonstrated that a liposomal array of well-ordered trimers enhances B cell activation, germinal center formation, and the elicitation of tier-2 autologous neutralizing antibodies. Previously, we coupled well-ordered cleavage-independent NFL trimers via their C-terminal polyhistidine tails to nickel lipids integrated into the lipid bilayer. Despite favorable in vivo effects, concern remained over the potentially longer-term in vivo instability of noncovalent linkage of the trimers to the liposomes. Accordingly, we tested both cobalt coupling and covalent linkage of the trimers to the liposomes by reengineering the polyhistidine tail to include a free cysteine on each protomer of model BG505 NFL trimers to allow covalent linkage. Both cobalt and cysteine coupling resulted in a high-density array of NFL trimers that was stable in both 20% mouse serum and 100 mM EDTA, whereas the nickel-conjugated trimers were not stable under these conditions. Binding analysis and calcium flux with anti-Env-specific B cells confirmed that the trimers maintained conformational integrity following coupling. Following immunization of mice, serologic analysis demonstrated that the covalently coupled trimers elicited Env-directed antibodies in a manner statistically significantly improved compared to soluble trimers and nickel-conjugated trimers. Importantly, the covalent coupling not only enhanced gp120-directed responses compared to soluble trimers, it also completely eliminated antibodies directed to the C-terminal His tag located at the “bottom” of the spike. In contrast, soluble and noncovalent formats efficiently elicited anti-His tag antibodies. These data indicate that covalent linkage of well-ordered trimers to liposomes in high-density array displays multiple advantages in vitro and in vivo. IMPORTANCE Enveloped viruses typically encode a surface-bound glycoprotein that mediates viral entry into host cells and is a primary target for vaccine design. Liposomes with modified lipid head groups have a unique feature of capturing and displaying antigens on their surfaces, mimicking the native pathogens. Our first-generation nickel-based liposomes captured HIV-1 Env glycoprotein trimers via a noncovalent linkage with improved efficacy over soluble glycoprotein in activating germinal center B cells and eliciting tier-2 autologous neutralizing antibodies. In this study, we report the development of second-generation cobalt- and maleimide-based liposomes that have improved in vitro stability over nickel-based liposomes. In particular, the maleimide liposomes captured HIV-1 Env trimers via a more stable covalent bond, resulting in enhanced germinal center B cell responses that generated higher antibody titers than the soluble trimers and liposome-bearing trimers via noncovalent linkages. We further demonstrate that covalent coupling prevents release of the trimers prior to recognition by B cells and masks a nonneutralizing determinant located at the bottom of the trimer.

Download Full-text

Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1606636113 ◽

2016 ◽

Vol 113 (24) ◽

pp. E3413-E3422 ◽

Cited By ~ 111

Author(s):

Hui Li ◽

Shuyi Wang ◽

Rui Kong ◽

Wenge Ding ◽

Fang-Hua Lee ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Germ Line ◽

Virus Entry ◽

Rhesus Macaques ◽

Critical Determinant ◽

Human Immunodeficiency Viruses ◽

Subtype A ◽

Hiv 1

Most simian–human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication and could be enhanced by substituting naturally occurring simian immunodeficiency virus Env residues at position 375, which resides at a critical location in the CD4-binding pocket and is under strong positive evolutionary pressure across the broad spectrum of primate lentiviruses. SHIVs containing primary or transmitted/founder HIV-1 subtype A, B, C, or D Envs with genotypic variants at residue 375 were constructed and analyzed in vitro and in vivo. Bulky hydrophobic or basic amino acids substituted for serine-375 enhanced Env affinity for rhCD4, virus entry into cells bearing rhCD4, and virus replication in primary rhCD4 T cells without appreciably affecting antigenicity or antibody-mediated neutralization sensitivity. Twenty-four RMs inoculated with subtype A, B, C, or D SHIVs all became productively infected with different Env375 variants—S, M, Y, H, W, or F—that were differentially selected in different Env backbones. Notably, SHIVs replicated persistently at titers comparable to HIV-1 in humans and elicited autologous neutralizing antibody responses typical of HIV-1. Seven animals succumbed to AIDS. These findings identify Env–rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors.

Download Full-text

New SHIVs and Improved Design Strategy for Modeling HIV-1 Transmission, Immunopathogenesis, Prevention and Cure

Journal of Virology ◽

10.1128/jvi.00071-21 ◽

2021 ◽

Author(s):

Hui Li ◽

Shuyi Wang ◽

Fang-Hua Lee ◽

Ryan S. Roark ◽

Alex I. Murphy ◽

...

Keyword(s):

T Cells ◽

Neutralizing Antibodies ◽

Large Scale ◽

Rhesus Macaques ◽

Passive Immunization ◽

Design Strategy ◽

Efficient Replication ◽

Hiv 1

Previously, we showed that substitution of HIV-1 Env residue 375-Ser by bulky aromatic residues enhances binding to rhesus CD4 and enables primary HIV-1 Envs to support efficient replication as simian-human immunodeficiency virus (SHIV) chimeras in rhesus macaques (RMs). Here, we test this design strategy more broadly by constructing SHIVs containing ten primary Envs corresponding to HIV-1 subtypes A, B, C, AE and AG. All ten SHIVs bearing wildtype Env375 residues replicated efficiently in human CD4+ T cells, but only one replicated efficiently in primary rhesus cells. This was a subtype AE SHIV that naturally contained His at Env375. Replacement of wildtype Env375 residues by Trp, Tyr, Phe or His in the other nine SHIVs led to efficient replication in rhesus CD4+ T cells in vitro and in vivo. Nine SHIVs containing optimized Env375 alleles were grown large-scale in primary rhesus CD4+ T cells to serve as challenge stocks in preclinical prevention trials. These virus stocks were genetically homogeneous, native-like in Env antigenicity and tier-2 neutralization sensitivity, and transmissible by rectal, vaginal, penile, oral or intravenous routes. To facilitate future SHIV constructions, we engineered a simplified second-generation design scheme and validated it in RMs. Overall, our findings demonstrate that SHIVs bearing primary Envs with bulky aromatic substitutions at Env375 consistently replicate in RMs, recapitulating many features of HIV-1 infection in humans. Such SHIVs are efficiently transmitted by mucosal routes common to HIV-1 infection and can be used to test vaccine efficacy in preclinical monkey trials. Importance SHIV infection of Indian rhesus macaques is an important animal model for studying HIV-1 transmission, prevention, immunopathogenesis and cure. Such research is timely, given recent progress with active and passive immunization and novel approaches to HIV-1 cure. Given the multifaceted roles of HIV-1 Env in cell tropism and virus entry, and as a target for neutralizing and non-neutralizing antibodies, Envs selected for SHIV construction are of paramount importance. Until recently, it has been impossible to strategically design SHIVs bearing clinically relevant Envs that replicate consistently in monkeys. This changed with the discovery that bulky aromatic substitutions at residue Env375 confer enhanced affinity to rhesus CD4. Here, we show that 10 new SHIVs bearing primary HIV-1 Envs with residue 375 substitutions replicated efficiently in RMs and could be transmitted efficiently across rectal, vaginal, penile and oral mucosa. These findings suggest an expanded role for SHIVs as a model of HIV-1 infection.

Download Full-text

Optimizing Lentiviral Transduction of Human Natural Killer Cells

Blood ◽

10.1182/blood.v118.21.4714.4714 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4714-4714 ◽

Cited By ~ 2

Author(s):

Su Su ◽

Dawn M Betters ◽

Muthalagu Ramanathan ◽

Keyvan Keyvanfar ◽

Aleah Smith ◽

...

Keyword(s):

Nk Cells ◽

Natural Killer ◽

Cell Line ◽

Nk Cell ◽

K562 Cells ◽

Cell Phenotype ◽

Human Renal Cell Carcinoma ◽

Hiv 1

Abstract Abstract 4714 The development of an efficient method to genetically modify natural killer (NK) cells could be used to characterize NK cell differentiation, acquisition of self-tolerance, tumor trafficking in vivo, as well as to manipulate NK cells to enhance their activity against infectious diseases and tumors. Although HIV-1 based lentiviral vectors (LVs) have been used to efficiently transfer genes into human T-cells, little data exists on LV transduction of either fresh or in vitro expanded human NK cells or its effects on NK cell phenotype and cytolytic function. In this study, we used an HIV-based LV expressing enhanced green fluorescence protein (EGFP) driven by a murine stem cell virus long terminal repeat (MSCV-LTR) promoter to transduce CD3− and CD56+ and/or CD16+ human NK cells that were either resting, IL-2 activated, or expanded in vitro using an irradiated EBV-LCL feeder cell line. We observed that resting NK cells were difficult to transduce with LVs, even at high multiplicities of infection (MOI), with transduction efficiencies (TE) in the range of only 3–14%. The efficiency of LV transduction improved when the NK cells were pre-stimulated in vitro with IL-2: TE improved to 21±0.2% in NK cells cultured for 24 hours in media containing IL-2 (200 U/mL) and 28.7±12.9% in NK cells that underwent in vitro expansion over 9 days prior to transduction using irradiated EBV-LCL feeder cells and media containing IL-2 (200U/mL). Subsequently, we evaluated incremental MOIs (3-200) to optimize LV transduction of expanded NK cells; optimal transduction was achieved using a spinoculation protocol at a MOI of 25 which resulted in the highest transduction efficiencies with the least amount of cell death. Increasing the MOI above this level resulted in a small increase in transduction, but was offset by an increase in NK cell apoptosis/death. Using a one-round, non-spinoculation protocol and an MOI of 30, we obtained a median transduction efficiency of 29% (range 16–41) with excellent retention of NK cell viability. This optimized protocol was used to transduce expanded NK cells with a LV vector encoding an shRNA targeting a region of the NK cell inhibitory receptor transcript NKG2A. Following transduction, surface expression of NKG2A decreased significantly on expanded NK cells compared to non-transduced expanded NK cells and “scramble transduced” LV controls; at a MOI of 10, the MFI of NKG2A on expanded human NK cells decreased 35% compared to non-transduced and LV transduced scramble controls (median MFI 428, 673, 659 in shRNA, non-transduced and scramble LV control transduced NK cells respectively). A comparison of transduction efficiencies using LVs expressing EGFP driven by MSCV-LTR, EF1a, and Ubi promoters showed MSCV-LTR mediated the highest level of gene expression in expanded NK cells. Transduced NK cells maintained stable EGFP transgene expression in vitro, which peaked 5 days following LV transduction and remained stable for an additional 9 days. The phenotype of lentiviral transduced NK cells was similar to non-transduced NK cells. Specifically, expression of CD56, CD16, granzyme A and B, perforin, the inhibitory receptors NKG2A, KIR3DL1, KIR3DL2, and KIR2DL1/DL2, and the activating receptors NKG2D, NCRs NKp46, and NKp30 were not altered in either fresh or expanded NK cells following LV transduction, although we did observe a significant reduction in NKp44 expression in LV transduced cells (22% compared to 50% on untransduced NK cells; 0.02). Furthermore, NK cell function, as assessed by cytokine production and cytotoxicity vs tumor targets was not altered in LV transduced NK cells. A 51Cr release cytotoxicity assay showed GFP+ NK cells, flow sorted following LV transduction of expanded NK cells, had similar cytotoxicity against K562 cells and human renal cell carcinoma cells (RCC) compared to non-transduced expanded NK cell controls (figures). In conclusion, we show that an HIV-1 based lentiviral vector driven by a MSCV-LTR, mediated efficient and stable gene transfer in IL-2 activated and in vitro expanded human NK cells. This study provides valuable insights for methods to optimize the long-term expression of LV transduced genes in human NK cells which could be used to improve their anti-tumor function in vivo. Target: K562 cells Target: RCC cell line Disclosures: No relevant conflicts of interest to declare.

Download Full-text

HIV-1-Based Virus-like Particles that Morphologically Resemble Mature, Infectious HIV-1 Virions

Viruses ◽

10.3390/v11060507 ◽

2019 ◽

Vol 11 (6) ◽

pp. 507 ◽

Cited By ~ 4

Author(s):

Christopher A. Gonelli ◽

Georges Khoury ◽

Rob J. Center ◽

Damian F.J. Purcell

Keyword(s):

T Cell ◽

Dna Vaccine ◽

Neutralizing Antibodies ◽

T Cell Responses ◽

Expression Vectors ◽

Virus Like Particles ◽

Cell Responses ◽

Hiv 1

A prophylactic vaccine eliciting both broad neutralizing antibodies (bNAbs) to the HIV-1 envelope glycoprotein (Env) and strong T cell responses would be optimal for preventing HIV-1 transmissions. Replication incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present authentic-structured, virion-associated Env to elicit bNAbs, and also stimulate T cell responses. Here, we optimize our DNA vaccine plasmids as VLP expression vectors for efficient Env incorporation and budding. The original vector that was used in human trials inefficiently produced VLPs, but maximized safety by inactivating RNA genome packaging, enzyme functions that are required for integration into the host genome, and deleting accessory proteins Vif, Vpr, and Nef. These original DNA vaccine vectors generated VLPs with incomplete protease-mediated cleavage of Gag and were irregularly sized. Mutations to restore function within the defective genes revealed that several of the reverse transcriptase (RT) deletions mediated this immature phenotype. Here, we made efficient budding, protease-processed, and mature-form VLPs that resembled infectious virions by introducing alternative mutations that completely removed the RT domain, but preserved most other safety mutations. These VLPs, either expressed from DNA vectors in vivo or purified after expression in vitro, are potentially useful immunogens that can be used to elicit antibody responses that target Env on fully infectious HIV-1 virions.

Download Full-text

Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo

Journal of Experimental Medicine ◽

10.1084/jem.20161160 ◽

2017 ◽

Vol 214 (9) ◽

pp. 2573-2590 ◽

Cited By ~ 74

Author(s):

Max Medina-Ramírez ◽

Fernando Garces ◽

Amelia Escolano ◽

Patrick Skog ◽

Steven W. de Taeye ◽

...

Keyword(s):

Crystal Structure ◽

B Cells ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Effective Vaccine ◽

Major Advance ◽

Cd4 Binding Site ◽

Hiv 1

Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resulting in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.

Download Full-text

SDF-1/CXCL12 Production by Mature Dendritic Cells Inhibits the Propagation of X4-Tropic HIV-1 Isolates at the Dendritic Cell-T-Cell Infectious Synapse

Journal of Virology ◽

10.1128/jvi.02449-09 ◽

2010 ◽

Vol 84 (9) ◽

pp. 4341-4351 ◽

Cited By ~ 17

Author(s):

Nuria González ◽

Mercedes Bermejo ◽

Esther Calonge ◽

Clare Jolly ◽

Fernando Arenzana-Seisdedos ◽

...

Keyword(s):

Dendritic Cells ◽

Lymph Nodes ◽

Neutralizing Antibodies ◽

Small Interfering Rnas ◽

Cxcl12 Expression ◽

Chemokine Production ◽

Hiv 1 ◽

Infectious Synapse

ABSTRACT An efficient mode of HIV-1 infection of CD4 lymphocytes occurs in the context of infectious synapses, where dendritic cells (DCs) enhance HIV-1 transmission to lymphocytes. Emergence of CXCR4-using (X4) HIV-1 strains occurs late in the course of HIV-1 infection, suggesting that a selective pressure suppresses the switch from CCR5 (R5) to X4 tropism. We postulated that SDF-1/CXCL12 chemokine production by DCs could be involved in this process. We observed CXCL12 expression by DCs in vivo in the parafollicular compartment of lymph nodes. The role of mature monocyte-derived dendritic cells (mMDDCs) in transmitting R5 and X4 HIV-1 strains to autologous lymphocytes was studied using an in vitro infection system. Using this model, we observed a strong enhancement of lymphocyte infection with R5, but not with X4, viruses. This lack of DC-mediated enhancement in the propagation of X4 viruses was proportional to CXCL12 production by mMDDCs. When CXCL12 activity was inhibited with specific neutralizing antibodies or small interfering RNAs (siRNAs), the block to mMDDC transfer of X4 viruses to lymphocytes was removed. These results suggest that CXCL12 production by DCs resident in lymph nodes represents an antiviral mechanism in the context of the infectious synapse that could account for the delayed appearance of X4 viruses.

Download Full-text

Different In Vivo Effects of HIV-1 Immunodominant Epitope-Specific Cytotoxic T Lymphocytes on Selection of Escape Mutant Viruses

Journal of Virology ◽

10.1128/jvi.02483-09 ◽

2010 ◽

Vol 84 (11) ◽

pp. 5508-5519 ◽

Cited By ~ 9

Author(s):

Hirokazu Koizumi ◽

Masao Hashimoto ◽

Mamoru Fujiwara ◽

Hayato Murakoshi ◽

Takayuki Chikata ◽

...

Keyword(s):

T Lymphocytes ◽

Cytotoxic T Lymphocytes ◽

Neutralizing Antibodies ◽

Escape Mutant ◽

Escape Mutants ◽

Hiv 1 ◽

Selection Of ◽

Strong Ability

ABSTRACT HIV-1 escape mutants are well known to be selected by immune pressure via HIV-1-specific cytotoxic T lymphocytes (CTLs) and neutralizing antibodies. The ability of the CTLs to suppress HIV-1 replication is assumed to be associated with the selection of escape mutants from the CTLs. Therefore, we first investigated the correlation between the ability of HLA-A*1101-restricted CTLs recognizing immunodominant epitopes in vitro and the selection of escape mutants. The result showed that there was no correlation between the ability of these CTLs to suppress HIV-1 replication in vitro and the appearance of escape mutants. The CTLs that had a strong ability to suppress HIV-1 replication in vitro but failed to select escape mutants expressed a higher level of PD-1 in vivo, whereas those that had a strong ability to suppress HIV-1 replication in vitro and selected escape mutants expressed a low level of PD-1. Ex vivo analysis of these CTLs revealed that the latter CTLs had a significantly stronger ability to recognize the epitope than the former ones. These results suggest that escape mutations are selected by HIV-1-specific CTLs that have a stronger ability to recognize HIV-1 in vivo but not in vitro.

Download Full-text

Comprehensive Cross-Clade Characterization of Antibody-Mediated Recognition, Complement-Mediated Lysis, and Cell-Mediated Cytotoxicity of HIV-1 Envelope-Specific Antibodies toward Eradication of the HIV-1 Reservoir

Journal of Virology ◽

10.1128/jvi.00634-17 ◽

2017 ◽

Vol 91 (16) ◽

Cited By ~ 15

Author(s):

Shariq Mujib ◽

Jun Liu ◽

A. K. M. Nur-ur Rahman ◽

Jordan A. Schwartz ◽

Phil Bonner ◽

...

Keyword(s):

T Cells ◽

Cd4 T Cells ◽

Neutralizing Antibodies ◽

Specific Antibodies ◽

Global Epidemic ◽

Infected Cells ◽

Hiv 1 ◽

Hiv Aids

ABSTRACT Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. In this study, we determined the ability of 12 well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1 belonging to clades A, B, C, and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro. We further tested unique combinations of these antibodies to determine the optimal antibody cocktails to be tested in future clinical trials. We report that antibody binding to infected CD4 T cells is highly variable and correlates with ADCML and ADCC processes. Particularly, antibodies targeting the envelope glycan shield (2G12) and V1/V2 site (PG9, PG16, and PGT145) are best at recognizing HIV-1-infected CD4 T cells. However, only PG9 and PG16 and their combinations with other bnAbs sufficiently induced the elimination of HIV-1-infected CD4 T cells by ADCML, ADCC, or both. Notably, CD4 binding site antibodies VRC01, 3BNC117, and NIH45-46 G54W did not exhibit recognition of infected cells and were unable to induce their killing. Future trials geared toward the development of a cure for HIV/AIDS should incorporate V1/V2 antibodies for maximal clearance of infected cells. With the use of only primary immune cells, we conducted a comprehensive cross-clade physiological analysis to aid the direction of antibodies as therapeutics toward the development of a cure for HIV/AIDS. IMPORTANCE Several antibodies capable of neutralizing the majority of circulating HIV-1 strains have been identified to date and have been shown to prevent infection in animal models. However, the use of combinations of such broadly neutralizing antibodies (bnAbs) for the treatment and eradication of HIV-1 in infected humans remains uncertain. In this study, we tested the ability of bnAbs to directly recognize and eliminate primary human CD4 T cells infected with diverse HIV-1 strains representative of the global epidemic by antibody-dependent pathways. We also tested several combinations of bnAbs in our assays in order to maximize the clearance of infected cells. We show that the ability of bnAbs to identify and kill infected cells is highly variable and that only a few of them are able to exert this function. Our data will help guide the formulation of bnAbs to test in future human trials aimed at the development of a cure.

Download Full-text