Research ArticleHIV

AAV-delivered eCD4-Ig protects rhesus macaques from high-dose SIVmac239 challenges

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Science Translational Medicine  24 Jul 2019:
Vol. 11, Issue 502, eaau5409
DOI: 10.1126/scitranslmed.aau5409

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Stepping up protection against SIV

HIV and the related simian immunodeficiency virus (SIV) enter cells through the CD4 receptor, so therapeutics have been designed based on CD4 to prevent viral binding and cell entry. Gardner et al. tested the ability of a modified CD4 protein to protect against a stringent SIV challenge. The protein, rh-eCD4-IgI39N, was delivered to nonhuman primates with an adeno-associated virus vector before repeated escalated SIVmac239 challenges. All control animals quickly became infected, but much higher doses were needed to infect rh-eCD4-IgI39N–treated animals. Subsequent analysis revealed that viral loads in the treated group were lower and that rh-eCD4-IgI39N puts selective pressure on SIV. Their results show that gene therapy with CD4-based proteins could protect against HIV infection.

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