eCD4-IG against HIV

CD4 has been known as the receptor for HIV since 1984. Various forms of stabilized CD4 which are tethered to human immunoglobulin molecules (eCD4-Ig) have been proposed and tested as potential therapeutics.  This idea is based on the fact that viral binding would neutralize the virus by preventing it from binding and entering the cells. However this approach failed bringing about another way of using human CD4 derivatives to prevent infection. The second approach involved engineering CD4 by fusing it with a mimetic of the amino terminus of CCR5. CCR5 is the host cell co-receptor used by most HIV-1 strains during infection and disease progression. The mimetic was based on an antibody that binds to the CCR5 binding site of the viral envelope. Ecd4-ig has potent and broad neutralizing activity against all HIV isolates ever tested including highly resistant viral strains. ECD4-Ig achieved neutralization effects at lower concentration when using the neutralizing monoclonal antibodies (NmAbs) that arise during the immune responses of some patients to HIV. Currently HIV vaccines that neutralize monoclonal antibodies are being preferred to those which modulate viraemia once infection has occurred. CD4 binding leads to a conformational change in the envelope of all HIV-1strains though at lower affinity than the super potent (Nmabs). The e-CD4I-g construct imparted resistance to HIV-1. ECD4 –I g use in humans raises questions on its safety (Haigwood, 2015).

Current research is being conducted in regards to eCD4-IG whereby monkeys and mice that model human HIV infections are used. The animals expressed the transgene stably and all animals were fully protected against repeated challenge with increasing doses of SHIV (aVirus combining parts of the simian immunodeficiency virus (SIV) and HIV genomes). The research also seeks to understand­ the safety of eCD4–Ig in humans (Haigwood, 2015).

References

Haigwood, N., l., (2015). News & Views: HIV-Tied Down by its own Receptor. Macmillan Publishers Limited, USA.