HIV-1 Envelope Evolution and Vaccine Efficacy

Abstract

Transmission of human immunodeficiency virus type 1 (HIV-1) selects for envelope variants with a number of defined properties, including use of CCR5 as the preferred coreceptor, binding to CCR5 in a distinct manner compared to HIV-1 isolated later in infection, shorter variable (V) regions, and fewer N-linked glycosylation sites. These features define the ideal target for an envelope-containing vaccine designed to elicit neutralizing antibody. If a candidate vaccine were sufficiently potent to elicit sterilizing immunity, virus evolution would not be an issue. However, all results to date suggest that an envelope-containing vaccine will have a lesser impact, and that virus evolution will contribute to escape from the vaccine-induced antibody response. The key question is whether or not the early selection pressure imposed by neutralizing antibody will have a long term impact on HIV disease progression. Several recent reports suggest that HIV-1 will evolve to rapidly escape antibody selection, and that the cost to the virus in terms of entry fitness will be small. Durable effects of vaccination are predicted to be associated with a reduction in peak viremia and viral set point at the time of primary infection.

Genetic Signatures of HIV-1 Envelope-mediated Bystander Apoptosis

“…The CD8 cytotoxic T cell response (29,30) and the neutralizing antibody production are largely responsible for the viral control leading into the chronic phase. During the chronic phase, the highest selection pressure due to neutralizing antibodies is on the Env glycoprotein of the virus (31), which undergoes rapid evolution via changes in the pattern of N-glycosylation and charge on the Env glycoprotein (32). Recently, several genetic signatures have been identified that can distinguish viruses from different stages of the disease that include but are not limited to changes in putative N-glycosylation sites (PNGS) (18,(32)(33)(34)(35).…”

Validation Processes of Protein Biomarkers in Serum—A Cross Platform Comparison

“…However, post-translational modified target antigens often contribute to diagnosis of autoimmune diseases like rheumatoid arthritis and systemic lupus erythematosus [15,16]. Post-translational glycosylation of antigens also represents an important target of anti-viral responses against HIV and influenza [17]. …”

Defining Carbohydrate Antigens as HIV Vaccine Candidates

“…Modification of the glycan shield under immunological pressure seems to afford a mechanism of immunological escape that allows the virus to persist in the presence of an evolving antibody repertoire [19,20]. Apparently there is immunologically mediated selection pressure both to change the position of individual glycans and to conserve the overall glycan shield of Env since mutations are selected that both destroy and create N glycosylation sites.…”