Beyond PrEP—immune technologies for prevention

Editor’s notes: Last month, we discussed developments in antibody technology.  This month there is a useful perspective paper in Science from Cohen and Corey that lays out the rationale and history of the development of broadly neutralising antibodies for the prevention of HIV.  Animal studies show that lower doses of antibody are needed to prevent HIV infection than to control it after the infection has occurred.  However, many animal studies are conducted with a narrow range of viruses in the infecting inoculum. Humans are generally exposed to a whole swarm of viruses, meaning that greater breadth of coverage may be needed to protect from infection.  Nonetheless, the rapid advances in synthesis of molecules that have additional active sites, such as the bioengineered triphasic antibody, combined with the ongoing proof of concept studies such as antibody-mediated prevention (AMP) mean that we can hope that biomedical prevention beyond PrEP is only just over the horizon.

Broadly neutralizing antibodies to prevent HIV-1.

Cohen MS, Corey L. Science. 2017 Oct 6;358(6359):46-47. doi: 10.1126/science.aap8131.

Advances in technology—especially single-cell antibody cloning techniques—have led to the isolation and characterization of antibodies from people with HIV infection that can neutralize many variants. These are referred to as broadly neutralizing antibodies (bnAbs). Such antibodies can be detected in about 25% of persons with untreated HIV-1 infection, reflecting a host immune response to unremitting viral replication, generation of large numbers of viral variants, and shifting antigen exposure. Although bnAbs may exert some selective pressure as they develop, they generally do not reduce viral burden, improve health, or slow the progression of disease. However, they offer considerable opportunities for treatment and prevention of HIV-1 infection in others. At this time, hundreds of bnAbs have been identified; those that have attracted the most attention are bnAbs with the greatest breadth, neutralizing the largest number of HIV-1 strains, including those traditionally most neutralization resistant; or bnAbs that have the greatest potency, requiring the smallest concentration to neutralize resistant strains of HIV-1.

Abstract access  [1]

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