Zika Virus and the World Health Organization Criteria for Determining Recent Infection Using Plaque Reduction Neutralization Testing

Ward, Matthew J.; Alger, Jackeline; Berrueta, Mabel; Bock, Harry; Buekens, Pierre; Cafferata, María Luisa; Ciganda, Álvaro; García, Jorge A.; García, Kimberly; López, Wendy; Lorenzana, Ivette; Parham, Leda; Wesson, Dawn M.

doi:10.4269/ajtmh.18-0237

Cited by 18 publications

(18 citation statements)

References 16 publications

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“…ZIKV plaque reduction neutralization tests (PRNTs) were conducted according to previously published protocols 18 , 19 . Briefly, ZIKV MEX-I-44 isolated in Tapachula, Mexico in 2016 was obtained from The University of Texas Medical Branch, Galveston, TX and cultured to passage 8 in Vero cells.…”

Section: Methodsmentioning

confidence: 99%

“…Plaque reduction neutralization tests. ZIKV plaque reduction neutralization tests (PRNTs) were conducted according to previously published protocols 18,19 www.nature.com/scientificreports/ Vero cells. Serum specimens were incubated for one hour at serial dilutions of 1:10, 1:20…1:320 with a previously frozen virus stock of known plaque forming unit (PFU).…”

Section: Intracellular Cytokine Stainingmentioning

confidence: 99%

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Immune outcomes of Zika virus infection in nonhuman primates

Schouest

Fahlberg

Scheef

et al. 2020

Sci Rep

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Although the Zika virus (ZIKV) epidemic is subsiding, immune responses that are important for controlling acute infection have not been definitively characterized. Nonhuman primate (NHP) models were rapidly developed to understand the disease and to test vaccines, and these models have since provided an understanding of the immune responses that correlate with protection during natural infection and vaccination. Here, we infected a small group of male rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques with a minimally passaged Brazilian ZIKV isolate and used multicolor flow cytometry and transcriptional profiling to describe early immune patterns following infection. We found evidence of strong innate antiviral responses together with induction of neutralizing antibodies and T cell responses. We also assessed the relative importance of CD8 T cells in controlling infection by carrying out CD8 T cell depletion in an additional two animals of each species. CD8 depletion appeared to dysregulate early antiviral responses and possibly increase viral persistence, but the absence of CD8 T cells ultimately did not impair control of the virus. Together, these data describe immunological trends in two NHP species during acute ZIKV infection, providing an account of early responses that may be important in controlling infection. Zika virus (ZIKV) has been a known pathogen for over half a century 1, but severe disease manifestations were not directly associated with the virus for most of its history. The recent outbreaks of ZIKV in the Western hemisphere became linked to neurologic and congenital syndromes that have provided strong incentives to develop prophylactic and therapeutic countermeasures. Several vaccine candidates spanning multiple platforms have performed well in preclinical studies and have advanced to clinical trials, but the waning of the epidemic has precluded efficacy testing in large populations 2,3. Additionally, an understanding of the immune responses that provide protection during natural infection is not yet complete, which also complicates our ability to evaluate whether vaccines will replicate these protective responses. The immunology of ZIKV infection has been most extensively studied in mice, and murine studies have shown the critical importance of type-I interferon (IFN) in limiting disease together with the protective roles of humoral and T cell responses 4-7. A growing body of literature also describes immune responses following ZIKV infection in nonhuman primates (NHPs), which are often used in preclinical vaccine studies 8 given their genetic and immunologic similarities to humans. Multiple species of macaques have been utilized, and these models replicate clinical aspects of viral infection and disease 9-13. However, the relative importance of innate and adaptive responses in controlling infection in monkeys is only beginning to be explored in depth, and this data is an important open question for the evaluation of candidate vaccines. Here, we carried out a descriptive anal...

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Section: Methodsmentioning

confidence: 99%

Section: Intracellular Cytokine Stainingmentioning

confidence: 99%

Immune outcomes of Zika virus infection in nonhuman primates

Schouest

Fahlberg

Scheef

et al. 2020

Sci Rep

Self Cite

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“…If the titer could not be calculated due to poor curve fitting, it was expressed as the last serum dilution showing a ≥ 50% and ≥ 90% reduction in plaque counts as compared with controls, respectively. A confirmed case of recent ZIKV infection was defined by positive anti-ZIKV IgM and ZIKV PRNT 90 titer ratio ≥ 4 compared to four DENV serotypes as defined by the World Health Organization [16]. A confirmed case of past ZIKV infection was defined using the same PRNT titer ratio criteria but negative anti-ZIKV IgM [17].…”

Section: Methodsmentioning

confidence: 99%

Low seroprevalence of Zika virus infection among adults in Southern Taiwan

Chien

Huang

et al. 2019

BMC Infect Dis

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BackgroundWe recently conducted a serosurvey of newly arrived workers in Taiwan from four Southeast Asian countries which revealed that 1% of the migrant workers had laboratory-confirmed recent Zika virus (ZIKV) infection. Taiwan, where Aedes mosquitoes are prevalent, has a close relationship with Southeast Asian countries. Up to now, 21 imported cases of ZIKV infection have been reported in Taiwan, but there has been no confirmed indigenous case. The aim of this serosurvey was to assess whether there was unrecognized ZIKV infections in Taiwan.MethodsA total of 212 serum samples collected in a cross-sectional seroepidemiologic study conducted during the end of the 2015 dengue epidemic in Tainan, Taiwan, were analyzed. Anti-ZIKV IgM and IgG were tested using commercial enzyme-linked immunosorbent assays (ELISAs). Plaque reduction neutralization tests (PRNTs) for ZIKV and four dengue virus (DENV) serotypes were performed for samples with positive anti-ZIKV antibodies. A confirmed case of ZIKV infection was defined by ZIKV PRNT90 titer ratio ≥ 4 compared to four DENV serotypes.ResultsThe mean age of the 212 participants was 54.0 years (standard deviation 13.7 years), and female was predominant (67.0%). Anti-ZIKV IgM and IgG were detected in 0 (0%) and 9 (4.2%) of the 212 participants, respectively. For the 9 samples with anti-ZIKV IgG, only 1 sample had 4 times higher ZIKV PRNT90 titers compared to PRNT90 titers against four dengue virus serotypes; this individual denied having traveled abroad.ConclusionsThe results suggest that undetected indigenous ZIKV transmission might have occurred in Taiwan. The findings also suggest that the threat of epidemic transmission of ZIKV in Taiwan does exist due to extremely low-level of herd immunity. Our study also indicates that serological tests for ZIKV-specific IgG remain a big challenge due to cross-reactivity, even in dengue non-endemic countries.

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“…While collecting baseline serologies would be ideal, this is too logistically challenging in our cohort, but may be considered for future studies. Moreover, it has been suggested that PRNT interpretation criteria may need to be adjusted for DENV-endemic areas [31], and how this should be taken into account for extended travel to a region should also be investigated. Since follow up of patients was not possible it cannot be ruled out that their course of disease lasted longer, or that viral shedding or persistence may have differed between groups.…”

Section: Discussionmentioning

confidence: 99%

Presence of Flavivirus Antibodies Does Not Lead to a Greater Number of Symptoms in a Small Cohort of Canadian Travelers Infected with Zika Virus

Kozak

Goneau

DeLima

et al. 2020

Viruses

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Zika virus (ZIKV) is a mosquito-borne flavivirus associated with a febrile illness as well as severe complications, including microcephaly and Guillain-Barré Syndrome. Antibody cross-reactivity between flaviviruses has been documented, and in regions where ZIKV is circulating, dengue virus (DENV) is also endemic, leaving the potential that previous exposure to DENV could alter clinical features of ZIKV infection. To investigate this, we performed a retrospective case-control study in which we compared Canadian travellers who had been infected with ZIKV and had serological findings indicating previous DENV or other flavivirus exposure (n = 16) to those without any previous exposure (n = 44). Patient samples were collected between February 2016 and September 2017 and submitted to Public Health Ontario for testing. ZIKV infection was determined using real-time RT-PCR and antibodies against DENV were identified by the plaque-reduction neutralization test. The mean time from symptom onset to sample collection was 5 days for both groups; the magnitude of viremia was not statistically different (Ct values: 35.6 vs. 34.9, p-value = 0.2). Clinical scores were also similar. Our findings indicate that previous DENV or other flavivirus exposure did not result in greater viremia or a higher illness score.

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Zika Virus and the World Health Organization Criteria for Determining Recent Infection Using Plaque Reduction Neutralization Testing

Cited by 18 publications

References 16 publications

Immune outcomes of Zika virus infection in nonhuman primates

Immune outcomes of Zika virus infection in nonhuman primates

Low seroprevalence of Zika virus infection among adults in Southern Taiwan

Presence of Flavivirus Antibodies Does Not Lead to a Greater Number of Symptoms in a Small Cohort of Canadian Travelers Infected with Zika Virus

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