Towards Multispecific Anti‐Gp120 Artificial Antibody

Broadly neutralizing antibodies are potential therapeutic drugs that can recognize and block viral entry. But many viruses, such as human immunodeficiency virus (HIV), mutate rapidly and thus evade therapeutic antibodies. Multispecific antibodies and combinations of different antibodies can effectively suppress immune evasion. However, many barriers hinder the development of multispecific antibodies, and the cost of combining multiple antibodies is very high. Previously, a class of gold nanoparticle (AuNP)-based artificial antibodies, called goldbodies, were created by simply grafting the complementary-determining regions of antibodies onto AuNPs. In this study, four monospecific anti-gp120 goldbodies are created by grafting the HIV gp120-binding fragment of the CD4 protein and the CDR3 loops of three anti-gp120 antibodies onto AuNPs, respectively. Remarkably, as a first proof of concept, the study shows that all four different fragments can be grafted onto the same AuNP particle, thus creating a new type of goldbody with a very high binding affinity for gp120. In principle, this new type of goldbody costs the same as a single monospecific goldbody, but it has the potential to serve as a multispecific goldbody or a combination of multiple goldbodies.