Human Immunodeficiency Virus (HIV)
HIV has a very fast replication cycle (producing 1010 virions every day) coupled with a high mutation rate of approximately 3 x 10−5 per nucleotide base per cycle of replication that leads to an unusually high genetic variability. This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day. Therefore, a true universal HIV vaccine needs to mount an antibody response against the mostly invariable regions of the viral coat, which are responsible for the docking of the virus and entry into the target cell. For HIV, these regions are epitopes of gp120, which bind to the dominant receptor CD4 and the co-receptor CCR5 on the surface of CD4+ lymphocytes. The receptor binding sites are thus a site of vulnerability of the HI virus, since they relate to a functional requirement for stable engagement with the receptors. The potential of such an approach was determined by several groups working with so-called broadly neutralizing antibodies (BnAbs) isolated from patients who are able to control their infection, which were given as passive immunotherapy. However, such an approach requires regular treatment with BnAbs for the rest of the patient’s life and may thus be prohibitively expensive in most parts of the world.
An active polyclonal IgG response to CD4 and/or CCR5 binding sites may therefore offer several advantages over passive immunotherapy with BnAbs. In fact, Viravaxx’s vaccine candidate VVX004 contains peptides derived from epitopes of gp120 that bind to the dominant receptor CD4 and the co-receptor CCR5 on the surface of CD4+ lymphocytes. The product is currently in lead optimization stage. With a prototype, elicitation of functional antibodies against gp120 has already been demonstrated after vaccination of rabbits.