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Impact of pre-existing dengue immunity on human antibody and memory B cell responses to Zika.

ABSTRACT: Little is known about enduring memory B cell (MBC) responses to Zika virus (ZIKV) and their relationship with circulating antibodies. Here we comprehensively assess MBC frequency and specificity alongside serum binding and neutralizing antibody responses to ZIKV ~2 weeks and ~8 months postinfection in 31 pediatric subjects with 0, 1 or >1 prior infections with the related dengue virus (DENV). ZIKV infection elicits a robust type-specific MBC response, and the majority of late convalescent anti-ZIKV serum neutralizing activity is attributable to ZIKV-specific antibodies. The number of prior DENV infections does not influence type-specific or cross-reactive MBC responses, although ZIKV has the highest cross-reactivity with DENV3. DENV cross-reactive MBCs expanded by ZIKV infection decline in number and proportion by late convalescence. Finally, ZIKV induces greater cross-reactivity in the MBC pool than in serum antibodies. Our data suggest immunity to DENV only modestly shapes breadth and magnitude of enduring ZIKV antibody responses.

SUBMITTER: Andrade P

PROVIDER: S-EPMC6391383 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Impact of pre-existing dengue immunity on human antibody and memory B cell responses to Zika.

Andrade Paulina P Gimblet-Ochieng Ciara C Modirian Faraz F Collins Matthew M Cárdenas Maritza M Katzelnick Leah C LC Montoya Magelda M Michlmayr Daniela D Kuan Guillermina G Balmaseda Angel A Coloma Josefina J de Silva Aravinda M AM Harris Eva E

Nature communications 20190226 1

Little is known about enduring memory B cell (MBC) responses to Zika virus (ZIKV) and their relationship with circulating antibodies. Here we comprehensively assess MBC frequency and specificity alongside serum binding and neutralizing antibody responses to ZIKV ~2 weeks and ~8 months postinfection in 31 pediatric subjects with 0, 1 or >1 prior infections with the related dengue virus (DENV). ZIKV infection elicits a robust type-specific MBC response, and the majority of late convalescent anti-Z ...[more]

PMID: 30808875

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Project description:The mosquito-borne Zika virus (ZIKV) has spread rapidly into regions where dengue virus (DENV) is endemic, and flavivirus cross-reactive T cell responses have been observed repeatedly in animal models and in humans. Preexisting cellular immunity to DENV is thought to contribute to protection in subsequent ZIKV infection, but the epitope targets of cross-reactive T cell responses have not been comprehensively identified. Using human blood samples from the regions of Nicaragua and Sri Lanka where DENV is endemic that were collected before the global spread of ZIKV in 2016, we employed an in vitro expansion strategy to map ZIKV T cell epitopes in ZIKV-unexposed, DENV-seropositive donors. We identified 93 epitopes across the ZIKV proteome, and we observed patterns of immunodominance that were dependent on antigen size and sequence identity to DENV. We confirmed the immunogenicity of these epitopes through a computational HLA binding analysis, and we showed that cross-reactive T cells specifically recognize ZIKV peptides homologous to DENV sequences. We also found that these CD4 responses were derived from the memory T cell compartment. These data have implications for understanding the dynamics of flavivirus-specific T cell immunity in areas of endemicity.IMPORTANCE Multiple flaviviruses, including Zika virus (ZIKV) and the four serotypes of dengue virus (DENV), are prevalent in the same large tropical and equatorial areas, which are inhabited by hundreds of millions of people. The interplay of DENV and ZIKV infection is especially relevant, as these two viruses are endemic in largely overlapping regions, have significant sequence similarity, and share the same arthropod vector. Here, we define the targets of preexisting immunity to ZIKV in unexposed subjects in areas where dengue is endemic. We demonstrate that preexisting immunity to DENV could shape ZIKV-specific responses, and DENV-ZIKV cross-reactive T cell populations can be expanded by stimulation with ZIKV peptides. The issue of potential ZIKV and DENV cross-reactivity is of relevance for understanding patterns of natural immunity, as well as for the development of diagnostic tests and vaccines.

Project description:Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers before and after immunization with inactivated whole-virion SARS-CoV-2 vaccines for COVID-19, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level pre-vaccination as well as the relationship between pre-existing sCoV immunity and vaccine-induced neutralization. We observed large amounts of pre-existing cross-reactive antibodies in the conserved regions among sCoVs, especially the S2 subunit. Excep t for a few peptides, the IgG and IgM fluorescence intensities against S, M and N peptides did not differ significantly between pre-vaccination and post-vaccination sera of vaccinees who developed a neutralization inhibition rate (%inhibition) <40 and %inhibition ≥40 after two doses of the COVID-19 vaccine. Participants with strong and weak pre-existing cross-reactive antibodies (strong pre-CRA; weak pre-CRA) had similar %inhibition pre-vaccination (10.9% ± 2.9% vs. 12.0% ± 2.2%, P=0.990) and post-vaccination (43.8% ± 25.1% vs. 44.6% ± 21.5%, P=0.997). Overall, the strong pre-CRA group did not show a significantly greater increase in antibody responses to the S protein linear peptides post-vaccination compared with the weak pre-CRA group. Therefore, we found no evidence for a significant impact of pre-existing antibody responses on inactivated vaccine-induced neutralization and antibody responses. Our research provides an important basis for inactivated SARS-CoV-2 vaccine use in the context of high sCoV seroprevalence.

Dataset Information

Impact of pre-existing dengue immunity on human antibody and memory B cell responses to Zika.

Publications

Impact of pre-existing dengue immunity on human antibody and memory B cell responses to Zika.

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