Flavivirus serocomplex cross-reactive immunity is protective by activating heterologous memory CD4 T cells

Abstract

Purpose:The discovery of Lloviu virus (LLOV) in Miniopterus schreibersii bat samples from Spain, 2003 dramatically changed our understanding of the genetic diversity, geographic distribution, and host preference of filoviruses. However, the ecology of LLOV is largely unclear mainly due to the lack of reports following the first report of LLOV. In our study, we try to solve the open questions regarding LLOV genetics and ecology, based on a continuous screening of a selected M. schreibersii colony, proved to be positive for LLOV during a mortality event in 2016. Methods & Materials:We established a countrywide surveillance system in Hungary for the early detection of M. schreibersii dye-offs in 2012 in collaboration with conservation bilogists and chiropterologists. In each case, carcasses were collected as soon as possible and transported to the laboratory in liquid nitrogen. Multiple events were examined during the past few years with viral metagenomic analyses and LLOV-specific TaqMan-based real-time PCR screening.Results: In 2016, we detected LLOV virus RNA in tissue samples of a M. schreibersii individual. Partial sequences of the nucleoprotein and the RNA-dependent RNA-polymerase gene suggests a close genetic relatedness with the original isolate in Spain. Following this event, several additional mortalities were registered to date in the same habitat with the same gross pathology of hemorrhagic symptoms, but no other positives were verified with PCR method, possibly because of the bad conditioned carcasses. In 2018, we started a monthly sampling activity, after the maternity period, in order to examine the seroprevalence, and other related factors of the virus in this cave.Conclusion: Here we present the current results of our survey programme, showing the relation of the Hungarian isolate to the original Spanish virus from 2003. A major goal of our presentation is to call attention to this pathogen, possibly affecting the stability of M. schreibersii colonies across Europe, representing a paramount concern for conservation biology. We discuss the possible factors leading to the dispersal of the virus in Europe and the possible transmission routes between bats to be examined in future studies and we also summarize current knowledge about the virus.

Transcriptomic immune profiles of human flavivirus‐specific T‐cell responses

“…YFV, JEV), multiple factors are challenging the design of protective vaccination against WNV, DENV, and ZIKV . Among those, the viral variability has a considerable impact, and is particularly important in the case of DENV, where the co‐circulation of multiple serotypes with only 50%–60% homology leads to heterologous infections strongly associated with increased risk of severe DENV disease …”

“…Additionally, co‐circulation of multiple flaviviruses in the same geographical areas is often observed, making it difficult to separate the immune response specific for a single flavivirus without considering the effect that previous flavivirus exposure or the following exposure can have in shaping the immune system, as previously reported between DENV and ZIKV . This observation also has implications in vaccine development, as in order to design an efficient vaccination able to protect from a specific flavivirus infection, it should be considered that the target populations are most likely flavivirus‐exposed.…”

When Can One Vaccinate with a Live Vaccine after Wild-Type Dengue Infection?

“…This is can be due to a "booster" effect linked to previous immunity and memory (for a review see [23]). Different mechanisms could be linked to such a booster effect, such as induction of cross-reactive CD4+ cells supporting cross-reactive B cell responses, as seen between different flaviviruses [37], and/or through a boosting effect linked to cross-reactive antibodies allowing a better vaccine take and infectivity. This has been seen for instance in subjects presenting a specific range of cross-reactive antibody titers from a prior inactivated Japanese encephalitis (JE) vaccination and then developing enhanced Yellow Fever (YF) immunogenicity upon YF17D vaccination [29].…”

The Global Distribution and Burden of Dengue and Japanese Encephalitis Co-Infection in Acute Encephalitis Syndrome

“…PA-AES shows a wide range of symptoms including headache, vomiting and severe illness, reduced consciousness, altered sensorium, convulsions, and tremors [12]. Flaviviruses share substantial sequence similarities to stimulate sero-cross-reactivity which results in the antibody-dependent enhancement (ADE) of infection with other flaviviruses [13].…”