Association of CR2 genotypes with the acquisition of HIV infection in a trial of recombinant glycoprotein 120 Vaccine.

Meza, Giovanna; Expósito, Almudena; Royo, José Luis; Ruiz-García, Celia; Sánchez-Arcas, Beatriz; Marquez, Francisco J; Gómez-Vidal, María Amparo; Omar, Mohamed; Sinangil, Faruk; Higgins, Keith; Forthal, Donald; Real, Luis Miguel; Caruz, Antonio

OBJECTIVES CR2 is the main receptor for complement protein C3 and plays an important role in adaptive immune responses. CR2 genetic variants are associated with susceptibility to systemic lupus erythematosus as well as to HIV-1 infection. Additionally, CR2 function can be subverted by HIV-1 for an efficient entry into target cells; in a process known as antibody-dependent enhancement of viral infection. We sought to determine the association between CR2 gene variants with HIV-1 acquisition after vaccination with recombinant gp120 protein (Vax004 clinical trial). DESIGN AND METHODS This is a retrospective cross-sectional study, comprising male subjects of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for 3 SNPs in the CR2 gene region. RESULTS An interaction was observed between the baseline sexual behaviour and the SNP rs3813946 for higher risk of infection in vacinees (interaction term p = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in subjects with low behavioral risk OR [95%CI]: 5.5 [1.4-21.7], p = 0.006 but not vaccinees with high behavioral risk or subjects given placebo (p = 0.7). Moreover, CR2 genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low risk subjects (Hazard odds ratio [95%CI]: 3.3 [1.6-7.0], p = 0.001). CONCLUSIONS This study suggests that CR2 may play a role in HIV-1 acquisition after vaccination with rgp120 proteins.