Synthetic carbohydrate-based HIV-1 vaccines

Forty years on: how close is an HIV vaccine?

“…HIV's notoriously high mutation rate -up to 10 nucleotide changes during each replication cycle -generates marked genetic diversity, which include numerous ways to evade the immune system's attention. 2,9 "HIV is genetically very variable across all the potential epitopes, including the binding sites for neutralising antibodies," Professor Geretti comments. (Neutralising antibodies bind to a virus and block infection.)…”

“…2 The proteins on the surface of HIV virions, which are the extracellular viral particles, have a large number of attached carbohydrates (glycosylation). 9 For example, each virion expresses between 7 and 14 'envelope spikes'. Each spike is a trimer of two glycoproteins: a surface subunit (gp120) and a transmembrane subunit (gp41) (see Figure 1).…”

“…2 So, a vaccine may need to generate bnAbs that block infection with several HIV-1 strains. 9 In the meantime, passive immunisation with bnAbs seem promising. 15 The Antibody Mediated Prevention (AMP) studies assessed the monoclonal antibody VRC01.…”

“…About 20% of people infected with HIV-1 produce circulating bnAbs as part of their natural immune response to HIV infection. 9 Several bnAbs seem to penetrate the carbohydrate shielding and bind to the prot e i n . O t h e r b n A b s b i n d t o t h e carbohydrate groups.…”

“…O t h e r b n A b s b i n d t o t h e carbohydrate groups. 9 Indeed, some bnAbs neutralise up to 99% of known HIV-1 isolates. 2 So, a vaccine may need to generate bnAbs that block infection with several HIV-1 strains.…”