Background: Secondary spread of hepatitis E virus (HEV) infection occurs often in endemic settings in developing countries. The host immune signatures contributing to protection against subsequent HEV reinfection are unknown.
Methods: Twelve seroconverted rhesus macaques were reinoculated with homologous HEV genotype 1 (gt1, Sar-55) and followed for 115 days. HEV RNA, HEV-specific T-cell responses, IgG anti-HEV antibody, and the IgG anti-HEV avidity index were tested.
Results: Four animals with baseline IgG anti-HEV levels from 1.5 to 13.4 World Health Organization (WHO) U/mL evidenced reinfection as determined by HEV RNA in stool, and increase in IgG anti-HEV levels between 63- and 285-fold (P = .003). Eight animals with baseline IgG anti-HEV levels from 2.8 to 90.7 WHO U/mL did not develop infection or shed virus in feces, and IgG anti-HEV antibody levels were unchanged (P = .017). The 4 reinfected animals showed a lower HEV-IgG avidity index (average 35.5%) than the 8 protected animals (average 62.1%). HEV-specific interferon-gamma-producing T cells were 2-fold higher in reinfected animals (P = .018).
Conclusions: Preexisting antibody and high IgG avidity index (>50%) are important factors for protection against HEV reinfection. HEV-specific T-cell responses were elevated in reinfected animals after subsequent exposure to HEV.
Keywords: IgG anti-HEV antibody; avidity of IgG anti-HEV antibody; genotype 1; hepatic host immune response gene expression; hepatitis E virus; reinfection; rhesus macaques.
Published by Oxford University Press for the Infectious Diseases Society of America 2018.