Repeated exposure to dengue virus elicits robust cross neutralizing antibodies against Zika virus in residents of Northeastern Thailand (original) (raw)
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The Journal of infectious diseases, 2018
The four dengue virus serotypes (DENV1-4) and Zika virus (ZIKV) are related mosquito-borne flaviviruses of major importance globally. While monoclonal antibodies and plasma from DENV-immune donors can neutralize or enhance ZIKV in vitro and in small animal models, and vice versa, the extent, duration, and significance of cross-reactivity remains unknown, particularly in flavivirus-endemic regions. We studied neutralizing antibodies to ZIKV and DENV1-4 in longitudinal serologic specimens through 3 years post-infection from people in Latin America and Asia with laboratory-confirmed DENV infections. We also evaluated neutralizing antibodies to ZIKV and DENV1-4 in Zika patients through 6 months post-infection. In Zika patients, the highest neutralizing antibody titers were to ZIKV, with low-level cross-reactivity to DENV1-4 that was greater in DENV-immune individuals. We found in primary and secondary DENV infections, neutralizing antibody titers to ZIKV were markedly lower than to the ...
Analysis of Zika virus neutralizing antibodies in normal healthy Thais
Scientific Reports
Zika virus (ZIKV) infections have been reported from all over Thailand, but the number of reported cases remains low, suggesting a degree of immune protection against ZIKV infection. To address this possibility, the presence of ZIKV neutralizing antibodies was determined in serum from 135 healthy Thai adults with a plaque reduction neutralization test (PRNT), and a number of samples were subsequently analyzed for the presence of neutralizing antibodies to dengue virus (DENV) and Japanese encephalitis virus (JEV). Results showed that 70.4% (PRNT 50 ≥ 10), 55.6 (PRNT 50 ≥ 20) or 22.2% (PRNT 90 ≥ 20) of the samples showed neutralizing antibodies to ZIKV. Detailed analysis showed no association between the presence of neutralizing antibodies to other flaviviruses (DENV, JEV) and the presence of ZIKV neutralizing antibodies. These results suggest that the level of ZIKV neutralizing antibodies in the Thai population is enough to dampen the transmission of the virus in Thailand. ZIKV was first isolated from a sentinel monkey in Zika forest Uganda in 1947 1 , and the virus was isolated from Aedes africanus mosquitoes in the same forest a year later 1. The first reported human case of ZIKV infection was reported nearly a decade later, with infection again occurring in Zika forest in Uganda 2,3. Between the initial identification of ZIKV and 2007 only a few sporadic cases of human ZIKV infection in Africa and Asia were reported (as reviewed elsewhere 4). In 2007 a small outbreak on the islands of Yap State in Micronesia represented the first time the virus was detected outside of Africa and Asia and analysis suggested this virus has originated in Southeast Asia 5. The virus again emerged from Southeast Asia in 2013 where it was detected as the causative agent in an outbreak of Zika fever in French Polynesia 6. The virus subsequently spread to many of the islands in the Pacific Ocean, and was detected in Brazil in March 2015 7,8 , and within one year more than a million cases of infection were reported. From Brazil the virus spread quickly to other countries in South, Central and North America (as reviewed elsewhere 4). While serological studies have suggested the presence of ZIKV in Southeast Asia for more than 60 years 9-11 , definitive evidence of the presence of the virus was first reported in 1966 12 , and the first virologically confirmed case of human infection was reported from Cambodia in 2010 13. In 2013 two tourists to Thailand were diagnosed on their return to their home countries with ZIKV infection 14,15 and a subsequent retrospective study by the Thai Ministry of Health confirmed that the virus was present in Thailand and causing disease in the local population 16 , with the earliest confirmed cases dating to infections occurring in 2012. Currently, some 1,600 cases of ZIKV infection are reported to have occurred in 2016 and 2017 by the Thai Ministry of Public Health 17. The basis of the markedly different population impact of ZIKV in the Americas and Southeast Asia remains unknown. At least three human pathogenic mosquito transmitted flavivirus circulate in Thailand, and in addition to ZIKV, both dengue virus (DENV) and Japanese encephalitis virus (JEV) circulate. DENV consists of four closely related, but antigenically distinct viruses 18 , termed DENV 1 to 4 all of which are endemic in Thailand 19. Currently the main public health problem caused by these viruses is infections with DENV, as there are an average of 50,000 cases per year in Thailand, and DENV infection is the leading cause of hospitalization amongst children in Southeast Asia 20. There is a national vaccination program to protect against JEV infections established in 1990 21 , however, JEV infection was the leading cause of hospitalizations for encephalitis in a study undertaken between 2003 and 2005 22. DENV infection induces protective immunity that lasts for many decades and possibly lifelong 23. However the immunity raised is against the homotypic virus only, and only limited or transient protection is generated against heterotypic DENV, and thus multiple infections with DENV are possible 24. Studies have shown that some 90% of Thai adults have antibodies against at least one DENV 25-27. Given the national JEV vaccination campaign, adults
mSphere, 2021
Thailand is a hyperendemic country for flavivirus infections in Southeast Asia. Although the reporting system for flavivirus surveillance in Thailand is well established, syndromic surveillance tends to underestimate the true epidemiological status of flaviviruses due to the majority of infections being asymptomatic. To accurately understand the prevalence of flaviviruses in endemic regions, we performed neutralization tests against multiple flaviviruses using 147 serum samples from healthy donors collected from four distinct regions in Thailand. Single-round infectious particles (SRIP) for six flaviviruses, dengue virus types 1 to 4 (DENV-1 to-4), Japanese encephalitis virus (JEV), and Zika virus (ZIKV), were used as antigens for developing a safe, high-throughput neutralization assay. Titers of neutralizing antibodies (NAbs) against the six flaviviruses revealed that DENV-1 and DENV-2, followed by ZIKV were the predominant circulating flaviviruses in a total of four regions, whereas the prevalence of NAbs against JEV varied among regions. Although the seroprevalence of ZIKV was low relative to that of DENV-1 and DENV-2, the findings strongly suggested that ZIKV has been circulating at a sustained level in Thailand since before 2012. These findings not only demonstrated the application of an SRIPneutralization test in a serological study, but also elucidated the circulation and distribution trends of different flaviviruses in Thailand. IMPORTANCE Neutralization tests are the most reliable assay for flavivirus antibody detection; however, these assays are not suitable for high-throughput processing due to their time-consuming and labor-intensive nature. In this study, we developed single-round infectious particles (SRIPs) with a luciferase gene for dengue virus types 1 to 4, Japanese encephalitis virus, and Zika virus for use in a safe, high-throughput neutralization assay. We performed neutralization tests against multiple flaviviruses using 147 serum samples that were collected from healthy donors residing in four distinct regions of Thailand in 2011 to 2012. The assay was useful for surveys of flavivirus seroprevalence. The data revealed that dengue virus type 1 (DENV-1) and DENV-2 were the predominant circulating flaviviruses in Thailand and that Zika virus has been circulating at a sustained level in Thailand since before 2012.
Impact of preexisting dengue immunity on Zika virus emergence in a dengue endemic region
Science, 2019
Zika dynamics in South America The infection dynamics of Zika virus (ZIKV) are difficult to characterize. Many ZIKV infections are asymptomatic, and the clinical presentation of ZIKV is nonspecific. Rodriguez-Barraquer et al. took advantage of a long-term health study under way in Salvador, Brazil, the epicenter of the recent outbreak in the Americas. They used multiple serological assays, from before and after the emergence of ZIKV in October 2015, to distinguish ZIKV immune responses from those against Dengue virus (DENV). About 73% of the population was attacked by ZIKV. The presence of preexisting antibodies to DENV was associated with less risk of ZIKV infection and fewer symptoms. Science , this issue p. 607
Scientific Reports, 2019
Despite the widespread presence of the mosquito transmitted Zika virus (ZIKV) over much of Southeast Asia, the number of reported cases remains low. One possibility is that residents in Southeast Asia are immunologically protected, although the nature of any such protection remains unclear. This study sought to investigate the presence of antibodies directed to ZIKV NS1 protein in a selected sub-set of samples from a well characterized cohort of serum samples from normal, healthy Thais that had been previously characterized for the presence of neutralizing antibodies to ZIKV, DENV 1-4, and JEV. Because of similarities in molecular weight between the flavivirus E and NS1 proteins, an immunoblot system was established in which the NS1 antigen was not denatured, allowing detection of the dimer form of NS1, distinctly clear from the migration position of the E and NS1 monomer proteins. The results showed that antibodies to ZIKV NS1 protein were only detected in samples with ZIKV neutral...
Viruses, 2018
The high levels of dengue-virus (DENV) seroprevalence in areas where the Zika virus (ZIKV) is circulating and the cross-reactivity between these two viruses have raised concerns on the risk of increased ZIKV disease severity for patients with a history of previous DENV infections. To determine the role of DENV preimmunity in ZIKV infection, we analyzed the T- and B-cell responses against ZIKV in donors with or without previous DENV infection. Using peripheral blood mononuclear cells (PBMCs) from donors living in an endemic area in Colombia, we have identified, by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) assay, most of the immunodominant ZIKV T-cell epitopes in the nonstructural (NS) proteins NS1, NS3, and NS5. Analyses of the T- and B-cell responses in the same donors revealed a stronger T-cell response against peptides conserved between DENV and ZIKV, with a higher level of ZIKV-neutralizing antibodies in DENV-immune donors in comparison with DENV-naïve donors. Strikin...
Journal of Immunology Research
Zika virus (ZIKV), an emerging mosquito-borne flavivirus, has quickly spread in many regions around the world where dengue virus (DENV) is endemic. This represents a major health concern, given the high homology between these two viruses, which can result in cross-reactivity. The aim of this study was to determine the cross-reacting antibody response of the IgM and IgG classes against the recombinant envelope protein of ZIKV (rE-ZIKV) in sera from patients with acute-phase infection of different clinical forms of dengue, i.e., dengue fever (DF) and dengue hemorrhagic fever (DHF) (before the arrival of ZIKV in Mexico 2010), as well as acute-phase sera of ZIKV patients, together with the implications in neutralization and antibody-dependent enhancement. Differences in IgM responses were observed in a number of DF and DHF patients whose sera cross-reacted with the rE-ZIK antigen, with 42% recognition between acute-phase DHF and ZIKV but 27% recognition between DF and ZIKV. Regarding Ig...
Zika virus infection enhances future risk of severe dengue disease
Science
The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challen...
2020
Background : Between 2016 and 2019, 265 cases of Zika virus (ZIKV) infection were reported in Vietnam, predominantly in southern Vietnam. In 2016, a case of ZIKV-associated microcephaly was confirmed in the Central Highlands, and several members of the infant’s family were confirmed to be infected with ZIKV. The study aims to determine the level of immunity to ZIKV in the general population of the ZIKV epidemic region. Methods: A total of 879 serum samples were collected from 801 participants between January 2017 and July 2018, during and after the ZIKV epidemic in Vietnam. The samples were tested for anti-ZIKV immunoglobulin M (IgM) and immunoglobulin G (IgG), and anti-dengue virus (DENV) IgG antibodies using enzyme-linked immunosorbent assays (ELISA). Plaque-reduction neutralization test (PRNT) for ZIKV was performed on all samples, and for DENV on the samples that ZIKV neutralizing antibody positive. Results: A total of 83 (10.3%) participants had anti-ZIKV IgM. Of the 83, 6 were...
Research Square (Research Square), 2023
Exposure to multiple mosquito-borne aviviruses within a lifetime is not uncommon; however, how sequential exposures to different aviviruses shape the cross-reactive (CR) humoral response against an antigen from a different serocomplex has yet to be explored. Here, we report that dengue-infected individuals initially primed with the Japanese encephalitis virus (JEV) showed broadly highly neutralizing potencies against the Zika virus (ZIKV). We also identi ed a rare class of ZIKV CR human monoclonal antibodies (huMAbs) with increased somatic hypermutation and broad neutralization against multiple aviviruses. One huMAb, K8b, binds quaternary epitopes with heavy and light chains separately interacting with overlapping E dimer units spanning domains I, II, and III through cryo-electron microscopy and structure-based mutagenesis. Using JEV virus-like particle (VLP) immunization in mice further con rmed that such CR antibodies, mainly IgG3 isotype, can be induced and proliferate through heterologous DENV-2 VLP stimulation. Our ndings provide novel insights for future vaccination strategies.