Evidence for Congenital Zika Virus Infection From Neutralizing Antibody Titers in Maternal Sera, Northeastern Brazil

Moreira-Soto, Andrés; Sarno, Manoel; Pedroso, Célia; Netto, Eduardo Martins; Rockstroh, Alexandra; Luz, Estela; Feldmann, Marie; Fischer, Carlo; Bastos, Fernanda Anjos; Kümmerer, Beate M.; Lamballerie, Xavier de; Drosten, Christian; Ulbert, Sebastian; Brites, Carlos; Drexler, Jan Felix

doi:10.1093/infdis/jix539

Cited by 26 publications

(38 citation statements)

References 15 publications

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“… ZIKV-specific and CHIKV-specific PRNT endpoint titers in humans and nonhuman primates. (A) ZIKV-specific PRNT endpoint titers in humans ( n = 122) as determined previously ( 37 ) using the same PRNT protocol as in this study, suggesting comparability of results. One sample with a titer of 1:25,000 is not shown for graphical reasons.…”

Section: Resultssupporting

confidence: 56%

“…However, plaque reduction neutralization test (PRNT) endpoint titers were invariably low at a 1:40 serum dilution for both ZIKV and CHIKV in all cases. For comparison, PRNT titers in ZIKV-infected humans can be several orders of magnitude higher using the same PRNT protocol ( 37 ) ( Fig. 2A ).…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, flaviviruses or alphaviruses other than those tested in this study may have elicited cross-reactive antibodies weakly neutralizing ZIKV and CHIKV at a 1:40 serum endpoint dilution, including St. Louis encephalitis virus, West Nile virus, and Eastern and Western equine encephalitis viruses, all of which are known to cause sporadic spillover infections in Neotropical NHP ( 47 ). Moreover, ZIKV-specific antibody titers were higher than 1:250 in 50% of tested humans using the same PRNT protocol ( 37 ), suggesting comparability of PRNT results between humans and NHP and highlighting the relatively low endpoint titers in NHP. Similarly, the fact that titers were invariably low and restricted to the screening dilution of sera is striking.…”

Section: Discussionmentioning

confidence: 98%

“…Similarly, the fact that titers were invariably low and restricted to the screening dilution of sera is striking. Normally, PRNT titers should vary on the population level, and they do so in experimental infections and in human cohorts ( 37 ). Importantly, the generally low seroprevalence and the absence of an increase in seroprevalence over time are in stark contrast with the intensive ZIKV spread in humans in the same areas, reaching about 60% during 2015 to 2016 in one of the sampling sites of this study ( 7 ).…”

Section: Discussionmentioning

confidence: 99%

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Limited Evidence for Infection of Urban and Peri-urban Nonhuman Primates with Zika and Chikungunya Viruses in Brazil

Moreira-Soto

Carneiro

Fischer

et al. 2018

mSphere

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Since 2013, Zika virus (ZIKV) and chikungunya virus (CHIKV) have infected millions of people in the Americas via urban transmission cycles. Nonhuman primates (NHP) are involved in sylvatic transmission cycles maintaining ZIKV and CHIKV in the Old World. We tested NHP sampled during 2012 to 2017 in urban and peri-urban areas severely affected by ZIKV and CHIKV in Brazil. Seroprevalence and antibody titers were low for both viruses. Additionally, we found evidence for infection by heterologous viruses eliciting cross-reactive antibodies. Our data suggest that urban or peri-urban NHP are not easily infected by ZIKV and CHIKV despite intense local transmission. These data may imply that the ZIKV and CHIKV outbreaks in the Americas cannot be sustained in urban or peri-urban NHP once human population immunity limits urban transmission cycles. Investigation of diverse animals is urgently required to determine the fate of the ZIKV and CHIKV outbreaks in the Americas.

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Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

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Limited Evidence for Infection of Urban and Peri-urban Nonhuman Primates with Zika and Chikungunya Viruses in Brazil

Moreira-Soto

Carneiro

Fischer

et al. 2018

mSphere

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“…PRNT was performed on acute-phase sera to detect neutralization antibody to ZIKV as reported previously (47). For late convalescent-phase sera, a previously described micro-neutralization test was performed (48).…”

Section: Methodsmentioning

confidence: 99%

T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

Herrera

Tsai

Brites

et al. 2018

Preprint

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WORD COUNT: 229 24 25 TEXT WORD COUNT: 3,409 26 27 (ZIKV) epidemic in the Americas and the Caribbean 49 demonstrates that clinical assays to detect, distinguish, and characterize immune 50 responses to flaviviral infections are needed. ZIKV and dengue virus (DENV) are 51 mosquito-transmitted flaviviruses sharing overlapping geographical distribution and 52have significant sequence similarity that can increase the potential for antibody and T 53 cell cross-reaction. Using nonstructural protein 1-based enzyme-linked immunosorbent 54 assays (ELISAs), we determine the serostatus of individuals living in a DENV-and 55 ZIKV-endemic region in Brazil, identifying individuals with primary DENV (pDENV) and 56 ZIKV (pZIKV), ZIKV with primary DENV (ZIKVwpDENV), and secondary DENV 57 (sDENV) infections; pDENV and pZIKV were further confirmed by neutralization tests. 58Development of an enzyme-linked immunospot (ELISPOT) assay for DENV and ZIKV 59 structural and nonstructural (NS) protein antigens enables us to distinguish infections by 60 these viruses based on T cells and to characterize those responses. We find that IFN-γ 61 and TNF-α T cell responses to NS3 differentiates DENV and ZIKV infections with 94% 62 sensitivity and 92% specificity. In general, we also show that pDENV and sDENV cases 63 and pZIKV and ZIKVwpDENV cases elicit similar T cell response patterns, and that HIV-64 infected individuals have T cell responses that are lower in magnitude compared to HIV-65 negative individuals. These results have important implications for DENV and ZIKV 66 diagnostic and vaccine development and provide critical insights into the T cell 67 response in individuals with multiple flaviviral infections. 68 69 4 IMPORTANCE 70 71 The potential for antibody and T cell cross-reaction to DENV and ZIKV, 72 flaviviruses that co-circulate and can sequentially infect individuals, has complicated 73 diagnostic and vaccine development. Our serological data show that antibodies to 74 nonstructural protein 1 can distinguish sequential human infections by DENV and ZIKV. 75 The development of a simple and inexpensive assay also enables the differentiation of 76 DENV and ZIKV infections based on the characterization of T cell responses. Our T cell 77 data reveals strong response patterns that are similar in nature in individuals with one or 78 multiple DENV infections and in individuals with only primary ZIKV infection and ZIKV-79 infected individuals with previous DENV exposure. The characterization of T cell 80 responses in a serologically-validated group of individuals is of relevance to the 81 development of vaccines and immunotherapeutics against these global threats. 82 83 84 85 86 87 88 89 90 91 92 93 94 Aedes mosquitoes transmit globally relevant flaviviruses including dengue virus 95 (DENV) and Zika virus (ZIKV). DENV exists as four antigenic serotypes, DENV1 to 96 DENV4 (1). These viruses have a wide geographic distribution with approximately 390 97 million infections annually and more than a quarter of the world's population at risk (2)...

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Epidemiological and clinical suspicion of congenital Zika virus infection: Serological findings in mothers and children from Brazil

Venturi

Fortuna

Alves³

et al. 2019

Journal of Medical Virology

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The emergence of Zika virus in the Americas has caused an increase of babies born with microcephaly or other neurological malformations. The differential diagnosis of Zika infection, particularly serological diagnosis, is an important but complex issue. In this study, we describe clinical manifestations of 94 suspected cases of congenital Zika from Bahia state, Brazil, and the results of serological tests performed on children and/or their mothers at an average of 71 days after birth. Anti‐Zika immunoglobulin M (IgM) antibodies were detected in 44.4% and in 7.1% of samples from mothers and children, respectively. Nearly all the IgM, and 92% of immunoglobulin G positive results were confirmed by neutralization test. Zika specific neutralizing antibodies were detected in as much as 90.4% of the cases. Moreover, dengue specific neutralizing antibodies were detected in 79.0% of Zika seropositive mothers. In conclusion, Zika IgM negative results should be considered with caution, due to a possible rapid loss of sensitivity after birth, while the NS1‐based Zika IgM enzyme‐linked immunosorbent assay test we have used has demonstrated to be highly specific. In a high percentage of cases, Zika specific neutralizing antibodies were detected, which are indicative of a past Zika infection, probably occurred during pregnancy in this population.

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Evidence for Congenital Zika Virus Infection From Neutralizing Antibody Titers in Maternal Sera, Northeastern Brazil

Cited by 26 publications

References 15 publications

Limited Evidence for Infection of Urban and Peri-urban Nonhuman Primates with Zika and Chikungunya Viruses in Brazil

Limited Evidence for Infection of Urban and Peri-urban Nonhuman Primates with Zika and Chikungunya Viruses in Brazil

T cell responses to nonstructural protein 3 distinguish infections by Dengue and Zika viruses

Epidemiological and clinical suspicion of congenital Zika virus infection: Serological findings in mothers and children from Brazil

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