HIV Broadly Neutralizing Antibodies: VRC01 and Beyond

Wu, Xueling

doi:10.1007/978-981-13-0484-2_3

Cited by 10 publications

(6 citation statements)

References 82 publications

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“…The majority of bNAbs isolated from HIV-infected patients have exceedingly high levels of somatic hypermutation (SHM) [5,26]. Accurately measuring levels of SHM elicited during immunization experiments is a critical component to ensuring the elicited antibodies are acquiring the level of mutations associated with neutralization breadth.…”

Section: Indian Origin Rhesus Macaque Bcr Germline Databasementioning

confidence: 99%

“…The HIV-1 envelope glycoprotein (Env) is the sole target for neutralizing antibody (NAb) responses. Studies of infected patients have led to the isolation of NAbs against multiple different epitopes on the Env surface that are capable of both neutralizing most circulating strains and providing passive protection against repeated viral challenges in non-human primates (NHPs) [2][3][4][5]. Extensive research efforts, including structure-based engineering of Env immunogens, are currently directed towards developing vaccine strategies to successfully elicit broadly neutralizing antibodies (bNAbs) against specific Env epitopes [6][7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

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Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

et al. 2020

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The induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several humanderived broadly neutralizing antibodies.

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Section: Indian Origin Rhesus Macaque Bcr Germline Databasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

et al. 2020

View full text Add to dashboard Cite

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“…The majority of bNAbs isolated from HIV-infected patients have exceedingly high levels of 90 somatic hypermutation (SHM) (Landais and Moore, 2018;Wu, 2018). Accurately measuring levels 91 of SHM elicited during immunization experiments is a critical component to ensuring the elicited 92 antibodies are acquiring the level of mutations associated with neutralization breadth.…”

Section: Indian Origin Rhesus Macaque Bcr Germline Database 89mentioning

confidence: 99%

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

Cottrell

Schooten

Bowman

et al. 2020

Preprint

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34The induction of broad and potent immunity by vaccines is the key focus of research efforts 35 aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins 36 have shown promise as vaccine candidates as they can induce potent autologous neutralizing 37 responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated 38 and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better 39 understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of 40 antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-41 epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 42 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and 43 have characteristics akin to several human-derived broadly neutralizing antibodies. 44 (nucleotide level) was 6.4% (range: 2.1%-10.2%) with an average HC complementarity-126 determining region 3 (CDR-H3) length of 15 amino acids (aa) (range: 7-23) ( Table S2). The rh1987 127 KC mAbs utilized HC variable genes from the IGHV3 and IGHV4 families and predominantly used 128 KC V genes from the IGKV1 family (Table S2). All of the rh1987 KC mAbs had a CDR-L3 length of 9 129 aa and their average KC SHM (nucleotide level) was 4.7% (range: 2.6%-6.0%) (Table S2). A single 130 clonal family with 4 members (RM19A) was detected among rh1987 KC mAbs with members 131 isolated from both week 22 and week 25 samples (Table S2). The rh1987 LC mAbs used HC V 132 genes from the IGHV1, IGHV3 and IGHV4 families and LC V genes mainly from the IGLV2 gene 133 family ( Table S2). The rh1987 LC mAbs had an average CDR-L3 length of 10 aa (range: 9-11) with 134 an average LC SHM (nucleotide level) of 3.8% (range: 0.9%-10.6%) (Table S2). Two clonal families 135

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“…Several promising broadly neutralizing antibodies have been identified targeting the HIV env protein and are demonstrating promising results for HIV treatment (reviewed in Ref. [128]). Pardi et al [49] encoded the HIV-VRC01 antibody into a nucleoside modified mRNA.…”

Section: Mrna-mabs Targeting Infectious Diseasesmentioning

confidence: 99%

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

2020

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Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others. Key PointsDirect in vivo delivery of synthetic nucleic acidencoded antibodies employing plasmid DNA [plasmid DNA-encoded monoclonal antibodies (pDNA-mAbs)] and messenger RNA-encoded monoclonal antibodies (mRNA-mAbs) platforms represent new approaches for the in vivo delivery of antibody-like biologics.While there are more preclinical data using pDNA-mAbs, both platforms have made significant progress and are demonstrating promising efficacy in infectious disease and cancer studies in small and large animal models.These platforms have advantages such as rapid product development and simpler manufacturing processes, yet they represent different strategies for deployment, with unique advantages and challenges.

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HIV Broadly Neutralizing Antibodies: VRC01 and Beyond

Cited by 10 publications

References 82 publications

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

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