Possible Impact of 190G > A CCR2 and Δ32 CCR5 Mutations on Decrease of the HBV Vaccine Immunogenicity-A Preliminary Report.

Abstract

Background: Chemokine genetic variations are involved in infectious diseases such as hepatitis B virus (HBV). Several allelic variants might, in theory, affect the outcome of vaccination. Objectives: This study was carried out to examine the associations of Δ32 CCR5 and 190G > A CCR2 polymorphisms with a response to a primary course of three HBV vaccinations. Methods: Between December 2014 and December 2016, patients from three randomly selected primary care clinics in the West Pomeranian region (Poland), 1 month after receiving the third dose of HBV vaccine, were enrolled. Enzyme-linked immunosorbent assay (ELISA) system version 3.0 was used to detect anti-HBs and anti-HBc totals. The identification of polymorphisms were performed by a polymerase chain reaction technique using a single primer extension assay. Genotype distributions of responders versus non-responders to HBV vaccination were compared on the basis of anti-HBs level. Results: In 149 patients (mean age 60 years) the mean anti-HBs level was 652.2 ± 425.9 mIU/mL (range: 0–1111.0 mIU/mL). There were 14.1% (n = 21) non-responders to the HBV vaccine (anti-HBs < 10.0 mIU/mL). The wild type/Δ32 genotype of CCR5 gene was found in 18.1% participants, and 1.3% were Δ32/Δ32 homozygotes. The frequency of allele A of the CCR2 gene was 11.1%. Lower anti-HBs levels in Δ32/Δ32 homozygotes were observed (Me = 61 mIU/mL vs. Me = 660.2 mIU/mL; p = 0.048). As age was found to be a correlate to the anti-HBs titer (r = −0.218, p = 0.0075; 95% CI: −0.366–−0.059)—an analysis of a co-variance was performed which found a statistically significant (p = 0.04) difference in anti-HBs titres between Δ32/Δ32 homozygotes and other CCR5 genotypes. The association between anti-HBs titres and CCR2 genotypes was not statistically significant. Conclusions: Our study—which is a preliminary report that suggest this topic deserves further observation with larger sample sizes, different ethnicities, and other single nucleotide poly-morphisms (SNPs)—suggests the possible involvement of CCR5 polymorphism in impairing the immunologic response to HBV vaccination, predominantly in relation to the passage of time.