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A single-gene encoded bispecific neutralizing antibody against diverse HIV infection

A single-gene encoded bispecific neutralizing antibody against diverse HIV infection. J. Guo 1 , M. An 1,2 , L. Cheng 1 , X. Wu 1 , H.Y. Tang 1 , H. Shang 2 , P. Zhou 3 , Z. Chen 1. Bispecific immunoadhesins (IAs) – PGT128 (Glycan-V3) & Hu5A8 (anti-CD4). 128. 128. 5A8. 128. 5A8.

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A single-gene encoded bispecific neutralizing antibody against diverse HIV infection

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  1. A single-gene encoded bispecific neutralizing antibody against diverse HIV infection J. Guo1, M. An1,2, L. Cheng1, X. Wu1, H.Y. Tang1, H. Shang2, P. Zhou3, Z. Chen1 • Bispecificimmunoadhesins (IAs) – PGT128 (Glycan-V3) & Hu5A8 (anti-CD4) 128 128 5A8 128 5A8 5A8 IA DG-bispecificIA SG-bispecificIA

  2. SG-Bi-IA: Improved neutralization breadth and potency compared to the parental IAs Breadth (%) 100 92 92 69 69 62 95 67 92 74 Median ± IQR Median ± IQR

  3. Conclusion • We engineered twotypes of bispecific IAs by combining the functional domains of Hu5A8 and PGT128 bNAbs. • SG-Bi-IA exhibited enhanced neutralization potency and 100% coverage of tested viruses, including the mutant viruses that resistant to both parental IAs. • Engineering of bispecific IA is an attractive way to improve anti-HIV properties of existing bNAbs, which have significant implications for antibody-based prophylactics in blocking diverse HIV-1 transmissions and infections. This work was supported by NSFC/RGC Joint Fund (N_HKU 709/11), HKU UDF, LKS Faculty of Medicine Matching Fund and China’s 12th Five-year National Science and Technology Mega Projects 2012ZX10001-009.

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