Broadly neutralizing antibodies targeting HIV: Progress and challenges

Paneerselvam, Nandagopal; Khan, Amber; Lawson, Brian R.

doi:10.1016/j.clim.2023.109809

Cited by 9 publications

(5 citation statements)

References 226 publications

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“…In recent years, several studies have revealed that broadly neutralizing antibodies against HIV-1 are a class of preventive antiviral drugs with advantages of high efficacy and few side effects, and they have shown promising antiviral effects in laboratory and clinical studies [ 26 , 27 , 28 , 29 ], indicating that these may be used as a supplement to the current antiretroviral HIV-1 drugs. A large number of HIV-1 bNAbs have been developed, including bNAbs that recognize various conserved epitopes on HIV-1 envelope glycoprotein, bNAbs that recognize HIV-1 cell receptors and co-receptors, as well as bispecific and trispecific antibodies engineered based on the above single antibodies [ 30 , 31 , 32 ]. One of the main reasons why HIV-1 can pose a significant challenge to humans is that HIV-1 is very easy to mutate and has many subtypes.…”

Section: Discussionmentioning

confidence: 99%

Rational Design and Characterization of Trispecific Antibodies Targeting the HIV-1 Receptor and Envelope Glycoprotein

Liang,

Zhai,

Liang

et al. 2023

Vaccines

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Multitudinous broadly neutralizing antibodies (bNAbs) against HIV-1 have been developed as novel antiviral prophylactic and therapeutic agents. Combinations of bNAbs are generally even more effective than when they are applied individually, showing excellent neutralization coverage and limiting the emergence of escape mutants. In this study, we investigated the design and characterization of three trispecific antibodies that allow a single molecule to interact with independent HIV-1 envelope determinants—(1) the host receptor CD4, (2) the host co-receptor CCR5 and (3) distinct domains in the envelope glycoprotein of HIV-1—using an ELISA, an HIV-1 pseudovirus neutralization assay and in vivo antiviral experiments in humanized mice. We found that trispecific bNAbs and monovalent ones all had satisfactory binding activities against the corresponding antigens in the ELISA, exhibited higher potency and breadth than any previously described single bnAb in the HIV-1 pseudovirus neutralization assay and showed an excellent antiviral effect in vivo. The trispecific antibodies simultaneously recognize the host receptor CD4, host co-receptor CCR5 and HIV-1 envelope glycoprotein, which could mean they have promise as prophylactic and therapeutic agents against HIV-1.

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Section: Discussionmentioning

confidence: 99%

Rational Design and Characterization of Trispecific Antibodies Targeting the HIV-1 Receptor and Envelope Glycoprotein

Liang,

Zhai,

Liang

et al. 2023

Vaccines

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“…Encouragingly, as some highly efficient bnAbs, GINPs have strong neutralizing potency against both tier 1 and tier 2 strains. It is also worth noting that the IC 50 values of GINPs were at comparable levels between tier 1 and tier 2 strains and much lower than that of a bnAb N6 (280 pM), 46,47 reflecting that GINPs may have an advantage over the first-class bnAbs in inhibiting HIV-1 infection.…”

Section: ■ Broad Antiviral Capability Of Ginpsmentioning

confidence: 98%

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition

Zhou,

Wang,

Liu

et al. 2024

Nano Lett.

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The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4 + immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1. The prepared envelope glycan-imprinted nanoparticles (GINPs) can successfully prevent HIV-1 from infecting target cells by shielding the glycans on the envelope protein. In vitro experiments showed that GINPs have strong affinity toward HIV-1 (K d = 36.7 ± 2.2 nM) and possess high anti-interference and specificity. GINPs demonstrate broad inhibition activity against both tier 1 and tier 2 HIV-1 strains with a pM-level IC 50 and exhibit a significant inhibitory effect on long-term viral replication by more than 95%. The strategy provides a promising method for the inhibition and therapy of HIV-1 infection.

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“…In another study by Casazza et al, the AAV8-mediated delivery of VRC01 resulted in the development of non-idiotypic ADAs directed against the Fab portion of VRC01 in three out of eight participants (37.5%), which appeared to decrease the production of VRC01 in two out these three participants [ 117 ]. A comprehensive overview of all the possible strategies to improve immunotherapy is reviewed in [ 28 ].…”

Section: Challenges Considerations and Improvementsmentioning

confidence: 99%

“…There are several conserved regions on the HIV-1-Env trimer that are particularly susceptible to neutralization, to which these bNAbs bind. These include the CD4-binding site, V3-glycan, V1/V2 glycan, gp41 membrane-proximal external region (MPER), gp120-gp41 interface, and the gp120 silent-face center [ 25 , 27 , 28 ] ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention

Thavarajah,

Hønge,

Wejse

2024

Viruses

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Background: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. Objective: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. Main findings: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a “proof of concept” for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.

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Broadly neutralizing antibodies targeting HIV: Progress and challenges

Cited by 9 publications

References 226 publications

Rational Design and Characterization of Trispecific Antibodies Targeting the HIV-1 Receptor and Envelope Glycoprotein

Rational Design and Characterization of Trispecific Antibodies Targeting the HIV-1 Receptor and Envelope Glycoprotein

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition

The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention

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