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Displaying record number 3313

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MAb ID	VRC01-LS (VRC01LS)
HXB2 Location	gp160	gp160 Epitope Map
Author Location
Epitope
Subtype	B
Ab Type	gp120 V2-CD4BS
Neutralizing	P
Species (Isotype)	human
Patient	NIH45
Immunogen	HIV-1 infection
Keywords	ADCC, antibody binding site, antibody generation, broad neutralizer, enhancing activity, immunoprophylaxis, immunotherapy, neutralization, review, therapeutic vaccine

Notes

Showing 7 of 7 notes.

VRC01-LS: This review focuses on the potential for bnAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines, or other novel therapeutics. Ongoing human trials aimed at HIV therapy or remission are utilizing the following antibodies, alone or in combination: VRC01, VRC01-LS, VRC07-523-LS, 3BNC117, 10-1074, 10-1074-LS, PGT121, PGDM1400, 10E8.4-iMab, and SAR441236 (trispecific VRC01/PGDM1400-10E8v4). Ongoing non-human primate studies aimed to target, control, or potentially eliminate the viral reservoir are utilizing the following antibodies, alone or in combination: 3BNC117, 10-1074, N6-LS, PGT121, and the GS9721 variant of PGT121. Hsu2021 (immunotherapy, review)
VRC01-LS: A series of mutants was produced in the CAP256-VRC26.25 heavy chain, for the purpose of avoiding the previously-identified proteolytic cleavage at position K100m. Neutralization of the mutants was tested, and the cleavage-resistant variant that showed the greatest potency was K100mA. In addition to the K100mA mutation, an LS mutation was added to the Fc portion of the heavy chain, as this change has been shown to improve the half-life of antibodies used for passive administration without affecting neutralization potency. The resulting construct was named CAP256V2LS. The pharmacokinetics of CAP256V2LS were assessed in macaques and mice, and it showed a profile similar to other antibodies used for immunotherapy. The antibody lacked autoreactivity. Structural analysis of wild-type CAP256-VRC26.25 showed that the K100m residue is not involved in interaction with the Env trimer. Neutralization data for VRC and VRC01-LS were used for comparison purposes. Zhang2022 (neutralization, immunotherapy, broad neutralizer)
VRC01-LS: VRC 606 (clinicaltrials.gov NCT02599896) was a single-site Phase I open-label dose-escalation study that evaluated a variant of VRC01, VRC01LS for safety and pharmacokinetic (PK) parameters. VRC01LS has mutations M428L and N434S in the Fc region intended to extend serum half-life, these LS mutations result in enhanced IgG-FcRn binding. It was observed that VRC01LS was safe and well tolerated and displayed a serum half-life more than four times longer than wild-type VRC01. The VRC01LS Ab retained its neutralizing activity in serum for the 48-week duration of this study, and no Abs were detected to it. The first 37 volunteers (healthy, HIV-negative) who received administrations of VRC01LS showed no serious adverse events (SAEs) or dose-limiting toxicities. The PK half life reported here from an LS mutation is comparable to those of Abs with the YTE mutation (M252Y/S254T/T256E); but in contrast the LS mutation does not significantly impact Fc-gamma binding and thus retains the Fc-mediated ADCC function of the antibody. Gaudinski2018 (ADCC, enhancing activity, therapeutic vaccine, immunotherapy, broad neutralizer)
VRC01-LS: This review discusses the identification of super-Abs, where and how such Abs may be best applied and future directions for the field. VRC01-LS is in Phase I clinical trial (Table 2). Walker2018 (antibody binding site, review, broad neutralizer)
VRC01-LS: This review focuses on the potential role of HIV-1-specific NAbs in preventing HIV-1 infection. Several NAbs have provided protection from infection in SHIV challenge studies in primates: b12, VRC01, VRC07-523LS, 3BNC117, PG9, PGT121, PGT126, 10-1074, 2G12, 4E10, 2F5, 10E8. Engineered variant VRC01-LS had greater persistence and improved protection against SHIV challenge, compared to VRC01. Pegu2017 (immunoprophylaxis, review)
VRC01-LS: VRC01 was modified by site-directed mutagenesis to increase its binding affinity for the neonatal Fc receptor (FcRn). One mutant, VRC01-LS, had enhanced binding. It carried two mutations of the heavy chain, M428L and N434S. Its neutralization and ADCC activities were similar to VRC01, and it had a longer serum half-life. In a SHIV challange, 10/12 macaques that received VRC01 were infected, in contrast to 5/12 VRC01-LS-injected macaques. Ko2014 (antibody generation, neutralization, immunotherapy)
VRC01-LS: Four bNAbs (VRC01, VRC01-LS, 3BNC117, and 10-1074) were administered, singly or in combination, to macaques, followed by weekly challenges with clade B SHIV_AD8. In all cases, the administration of MAbs delayed virus acquisition. Control animals required 2 to 6 challenges before becoming infected, while animals receiving VRC01 required 4–12 challenges; 3BNC117 required 7–20 challenges; 10-1074 required 6–23 challenges; and VRC01-LS required 9–18 challenges. Animals that received a single antibody infusion resisted infection for up to 23 weekly challenges. Gautam2016 (immunotherapy)

References

Showing 7 of 7 references.

Isolation Paper
Ko2014 Sung-Youl Ko, Amarendra Pegu, Rebecca S. Rudicell, Zhi-yong Yang, M. Gordon Joyce, Xuejun Chen, Keyun Wang, Saran Bao, Thomas D. Kraemer, Timo Rath, Ming Zeng, Stephen D. Schmidt, John-Paul Todd, Scott R. Penzak, Kevin O. Saunders, Martha C. Nason, Ashley T. Haase, Srinivas S. Rao, Richard S. Blumberg, John R. Mascola, and Gary J. Nabel. Enhanced Neonatal Fc Receptor Function Improves Protection against Primate SHIV Infection. Nature, 514(7524):642-645, 30 Oct 2014. PubMed ID: 25119033. Show all entries for this paper.

Gaudinski2018 Martin R. Gaudinski, Emily E. Coates, Katherine V. Houser, Grace L. Chen, Galina Yamshchikov, Jamie G. Saunders, LaSonji A. Holman, Ingelise Gordon, Sarah Plummer, Cynthia S. Hendel, Michelle Conan-Cibotti, Margarita Gomez Lorenzo, Sandra Sitar, Kevin Carlton, Carolyn Laurencot, Robert T. Bailer, Sandeep Narpala, Adrian B. McDermott, Aryan M. Namboodiri, Janardan P. Pandey, Richard M. Schwartz, Zonghui Hu, Richard A. Koup, Edmund Capparelli, Barney S. Graham, John R. Mascola, Julie E. Ledgerwood, and VRC 606 Study Team. Safety and Pharmacokinetics of the Fc-Modified HIV-1 Human Monoclonal Antibody VRC01LS: A Phase 1 Open-Label Clinical Trial in Healthy Adults. PLoS Med., 15(1):e1002493, Jan 2018. PubMed ID: 29364886. Show all entries for this paper.

Gautam2016 Rajeev Gautam, Yoshiaki Nishimura, Amarendra Pegu, Martha C. Nason, Florian Klein, Anna Gazumyan, Jovana Golijanin, Alicia Buckler-White, Reza Sadjadpour, Keyun Wang, Zachary Mankoff, Stephen D. Schmidt, Jeffrey D. Lifson, John R. Mascola, Michel C. Nussenzweig, and Malcolm A. Martin. A Single Injection of Anti-HIV-1 Antibodies Protects against Repeated SHIV Challenges. Nature, 533(7601):105-109, 5 May 2016. PubMed ID: 27120156. Show all entries for this paper.

Pegu2017 Amarendra Pegu, Ann J. Hessell, John R. Mascola, and Nancy L. Haigwood. Use of Broadly Neutralizing Antibodies for HIV-1 Prevention. Immunol. Rev., 275(1):296-312, Jan 2017. PubMed ID: 28133803. Show all entries for this paper.

Walker2018 Laura M. Walker and Dennis R. Burton. Passive Immunotherapy of Viral Infections: `Super-Antibodies' Enter the Fray. Nat. Rev. Immunol., 18(5):297-308, May 2018. PubMed ID: 29379211. Show all entries for this paper.

Zhang2022 and Jason Gorman Baoshan Zhang. Engineering of {HIV-1} Neutralizing Antibody {CAP256V2LS} for Manufacturability and Improved Half life. , :, 22 Apr 2022. Show all entries for this paper.

Hsu2021 Denise C. Hsu, John W. Mellors, and Sandhya Vasan. Can Broadly Neutralizing HIV-1 Antibodies Help Achieve an ART-Free Remission? Front Immunol, 12:710044 doi, 2021. PubMed ID: 34322136 Show all entries for this paper.