Evaluation of autophagy induction on HEV 239 vaccine immune response in a mouse model.

Hepatitis E virus (HEV) infection remains a serious threat to life and productivity in developing world. Vaccine seems to be an effective, safe, and affordable approach to address HEV disease burden. The HEV genome consists of three open reading frames (ORFs). Of these, ORF2 encodes a single structural protein (pORF2) for the HEV capsid which has been studied extensively as vaccine candidates. Recently, it has been recognized that autophagy plays an important role in innate and adaptive immunity defense against intracellular pathogens. This mechanism could therefore promote a protective immune response by inducing CD4+ and CD8+ T cells. In this study, HEV 239 and Beclin1 proteins were expressed in prokaryotic host cell [Escherichia coli (BL21)]. HEV 239 protein with different formulations (+Alum, +Beclin1, and +Alum-Beclin1) were used as candidate vaccines and administrated subcutaneously in BALB/c mice on 0, 14, and 28 days. Finally, elicited cellular and humoral immunity were evaluated. Taken together, although our results indicated that mice immunized with HEV 239 protein formulated with Alum, Beclin1, and Alum + Beclin1 displayed humoral and cellular response that was not significant in comparison with each other (P > 0.05); whereas they were significant while compared with control groups (P < 0.05). A comprehensive understanding of the intricate interplay between autophagy and immune response remains to be unraveled. Further study will clear the detailed impact of autophagy manipulation to enhance vaccine efficacy and boost the immune responses against the disease. © 2018 IUBMB Life, 70(3):207-214, 2018.

Evaluation of possible relationship between COL4A4 gene polymorphisms and risk of keratoconus.

PURPOSE: Keratoconus (KC) is a genetically heterogeneous corneal dystrophy with unknown etiology that causes loss of visual acuity. Evidence has shown that corneas from patients with KC contain reduced amounts of total collagen proteins, and collagen type IV has been suggested as a candidate gene in KC pathogenesis. This study aimed to evaluate the possible associations between collagen type IV alpha-4 chain (COL4A4) polymorphisms (rs2229813 G/A, M1327V and rs2228555 A/G, V1516V) and susceptibility to KC. METHODS: A total of 262 Iranian subjects including 112 patients with KC and 150 healthy individuals as controls were recruited in this case-control study. Diagnosis was based on clinical examination, electronic refractometry, and keratometry. Genotyping for the COL4A4 rs2229813 and rs2228555 variants was executed using allele-specific polymerase chain reaction and Tetra-ARMS polymerase chain reaction, respectively. RESULTS: A significant difference was found between the 2 groups regarding allelic and genotyping distribution of COL4A4 polymorphism at position rs2229813 G>A. The COL4A4 rs2229813 AA and GA+AA genotypes were risk factors for developing KC (odds ratio [OR] = 2.1, P = 0.036 and OR = 1.7, P = 0.042, for the AA and GA+AA genotypes, respectively). The COL4A4 rs2229813 A allele was also associated with an increased risk for KC (OR = 1.5, 95% confidence intervals: 1.1-2.2, P = 0.018). However, in our study, we found no association between COL4A4 rs2228555 polymorphism and the risk of KC. CONCLUSIONS: We suggest that the COL4A4 rs2229813 AA and GA+AA genotypes as well as the A allele play roles as risk factors for developing KC in our population.