Association of Complement C3d Receptor 2 Genotypes with the Acquisition of HIV Infection in a Trial of Recombinant Glycoprotein 120 Vaccine.

Objectives: Complement C3d receptor 2 (CR2) is the main receptor for complement protein C3d 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. In addition, 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 betweenCR2gene 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 volunteers of European ancestry including infected (n = 273) and uninfected (n = 402) vaccinees and placebo, who were genotyped for three single nucleotide polymorphisms (SNPs) in theCR2gene region. Results: An interaction was observed between the baseline sexual behavior and the SNP rs3813946 for higher risk of infection in vacinees (interaction termP = 0.02). This SNP was associated with increased susceptibility to HIV-1 infection after vaccination in volunteers with low behavioral risk odds ratio (95% confidence interval): 5.5 (1.4-21.7)P = 0.006 but not vaccinees with high behavioral risk or volunteers given placebo (P = 0.7). Moreover,CR2genotype was strongly associated with the rate of HIV-1 acquisition after vaccination in low-risk volunteers [hazard odds ratio (95% confidence interval): 3.3 (1.6-7.0),P = 0.001]. Conclusion: The current study suggests thatCR2may play a role in HIV-1 acquisition after vaccination with rgp120 proteins.