Corrigendum: Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection

Zika virus (ZIKV) has recently caused explosive outbreaks in Pacific islands, South- and Central America. Like with other flaviviruses, protective immunity is strongly dependent on potently neutralizing antibodies (Abs) directed against the viral envelope protein E. Such Ab formation is promoted by CD4 T cells through direct interaction with B cells that present epitopes derived from E or other structural proteins of the virus. Here, we examined the extent and epitope dominance of CD4 T cell responses to capsid (C) and envelope proteins in Zika patients. All patients developed ZIKV-specific CD4 T cell responses, with substantial contributions of C and E. In both proteins, immunodominant epitopes clustered at sites that are structurally conserved among flaviviruses but have highly variable sequences, suggesting a strong impact of protein structural features on immunodominant CD4 T cell responses. Our data are particularly relevant for designing flavivirus vaccines and their evaluation in T cell assays and provide insights into the importance of viral protein structure for epitope selection and antigenicity.(VLID)470226

Different Cross-Reactivities of IgM Responses in Dengue, Zika and Tick-Borne Encephalitis Virus Infections

Flaviviruses circulate worldwide and cause a number of medically relevant human diseases, such as dengue, Zika, yellow fever, and tick-borne encephalitis (TBE). Serology plays an important role in the diagnosis of flavivirus infections, but can be impeded by antigenic cross-reactivities among flaviviruses. Therefore, serological diagnosis of a recent infection can be insufficiently specific, especially in areas where flaviviruses co-circulate and/or vaccination coverage against certain flaviviruses is high. In this study, we developed a new IgM assay format, which is well suited for the specific diagnosis of TBE, Zika and dengue virus infections. In the case of TBE and Zika, the IgM response proved to be highly specific for the infecting virus. In contrast, primary dengue virus infections induced substantial amounts of cross-reactive IgM antibodies, which is most likely explained by structural peculiarities of dengue virus particles. Despite the presence of cross-reactive IgM, the standardized nature and the quantitative read-out of the assay even allowed the serotype-specific diagnosis of recent dengue virus infections in most instances

Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection

Zika virus (ZIKV) has recently caused explosive outbreaks in Pacific islands, South- and Central America. Like with other flaviviruses, protective immunity is strongly dependent on potently neutralizing antibodies (Abs) directed against the viral envelope protein E. Such Ab formation is promoted by CD4 T cells through direct interaction with B cells that present epitopes derived from E or other structural proteins of the virus. Here, we examined the extent and epitope dominance of CD4 T cell responses to capsid (C) and envelope proteins in Zika patients. All patients developed ZIKV-specific CD4 T cell responses, with substantial contributions of C and E. In both proteins, immunodominant epitopes clustered at sites that are structurally conserved among flaviviruses but have highly variable sequences, suggesting a strong impact of protein structural features on immunodominant CD4 T cell responses. Our data are particularly relevant for designing flavivirus vaccines and their evaluation in T cell assays and provide insights into the importance of viral protein structure for epitope selection and antigenicity

Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans

Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals

Data_Sheet_1_Structural Influence on the Dominance of Virus-Specific CD4 T Cell Epitopes in Zika Virus Infection.PDF

<p>Zika virus (ZIKV) has recently caused explosive outbreaks in Pacific islands, South- and Central America. Like with other flaviviruses, protective immunity is strongly dependent on potently neutralizing antibodies (Abs) directed against the viral envelope protein E. Such Ab formation is promoted by CD4 T cells through direct interaction with B cells that present epitopes derived from E or other structural proteins of the virus. Here, we examined the extent and epitope dominance of CD4 T cell responses to capsid (C) and envelope proteins in Zika patients. All patients developed ZIKV-specific CD4 T cell responses, with substantial contributions of C and E. In both proteins, immunodominant epitopes clustered at sites that are structurally conserved among flaviviruses but have highly variable sequences, suggesting a strong impact of protein structural features on immunodominant CD4 T cell responses. Our data are particularly relevant for designing flavivirus vaccines and their evaluation in T cell assays and provide insights into the importance of viral protein structure for epitope selection and antigenicity.</p