AAV-Mediated Expression of Broadly Neutralizing and Vaccine-like Antibodies Targeting the HIV-1 Envelope V2 Region.

AAV-Mediated Expression of Broadly Neutralizing and Vaccine-like Antibodies Targeting the HIV-1 Envelope V2 Region.

van den Berg, Fiona T;Makoah, Nigel A;Ali, Stuart A;Scott, Tristan A;Mapengo, Rutendo E;Mutsvunguma, Lorraine Z;Mkhize, Nonhlanhla N;Lambson, Bronwen E;Kgagudi, Prudence D;Crowther, Carol;Abdool Karim, Salim S;Balazs, Alejandro B;Weinberg, Marc S;Ely, Abdullah;Arbuthnot, Patrick B;Morris, Lynn;
molecular therapy methods & clinical development 2019 Vol. 14 pp. 100-112
279
van-den-berg2019aavmediatedmolecular

Abstract

HIV-1 infection continues to be a global health challenge and a vaccine is urgently needed. Broadly neutralizing antibodies (bNAbs) are considered essential as they inhibit multiple HIV-1 strains, but they are difficult to elicit by conventional immunization. In contrast, non-neutralizing antibodies that correlated with reduced risk of infection in the RV144 HIV vaccine trial are relatively easy to induce, but responses are not durable. To overcome these obstacles, adeno-associated virus (AAV) vectors were used to provide long-term expression of antibodies targeting the V2 region of the HIV-1 envelope protein, including the potent CAP256-VRC26.25 bNAb, as well as non-neutralizing CAP228 antibodies that resemble those elicited by vaccination. AAVs mediated effective antibody expression in cell culture and immunocompetent mice. Mean concentrations of human immunoglobulin G (IgG) in mouse sera increased rapidly following a single AAV injection, reaching 8-60 μg/mL for CAP256 antibodies and 44-220 μg/mL for CAP228 antibodies over 24 weeks, but antibody concentrations varied for individual mice. Secreted antibodies collected from serum retained the expected binding and neutralizing activity. The vectors generated here are, therefore, suitable for the delivery of V2-targeting HIV antibodies, and they could be used in a vectored immunoprophylaxis (VIP) approach to sustain the level of antibody expression required to prevent HIV infection.

Citation

ID: 17776
Ref Key: van-den-berg2019aavmediatedmolecular
Use this key to autocite in SciMatic or Thesis Manager

References

Blockchain Verification

Account:
NFT Contract Address:
0x95644003c57E6F55A65596E3D9Eac6813e3566dA
Article ID:
17776
Unique Identifier:
10.1016/j.omtm.2019.06.002
Network:
Scimatic Chain (ID: 481)
Loading...
Blockchain Readiness Checklist
Authors
Abstract
Journal Name
Year
Title
5/5
Creates 1,000,000 NFT tokens for this article
Token Features:
  • ERC-1155 Standard NFT
  • 1 Million Supply per Article
  • Transferable via MetaMask
  • Permanent Blockchain Record
Blockchain QR Code
Scan with Saymatik Web3.0 Wallet

Saymatik Web3.0 Wallet