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1.
Nat Commun ; 15(1): 5833, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992033

ABSTRACT

Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale.


Subject(s)
Antibodies, Viral , Arboviruses , Humans , Arboviruses/immunology , Arboviruses/isolation & purification , Animals , Antibodies, Viral/immunology , Antibodies, Viral/blood , Peptides/immunology , Peptides/chemistry , Zika Virus Infection/virology , Zika Virus Infection/immunology , Zika Virus Infection/blood , Zika Virus/immunology , Epitopes/immunology , Serologic Tests/methods , Arbovirus Infections/virology , Arbovirus Infections/immunology , Proteome , Colombia , Female , Peptide Library , Cell Surface Display Techniques , Male
2.
Indian J Public Health ; 68(2): 163-166, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38953800

ABSTRACT

BACKGROUND: Several sporadic cases and outbreaks of Zika virus disease have been reported from different states of India. OBJECTIVES: This paper explored the possibility of any ongoing transmission of Zika virus (ZIKV) in the Bhopal region of Central India, where the last outbreak of this disease was reported in 2018. MATERIALS AND METHODS: We screened a group of 75 febrile patients who had already tested negative for the locally endemic causes of fever like dengue, chikungunya, enteric fever, malaria, and scrub typhus and two groups of asymptomatic healthy individuals represented by blood donors (n = 75) and antenatal mothers (n = 75). We tested blood samples of febrile patients for ZIKV RNA using real-time polymerase chain reaction (PCR), and for the healthy individuals, we determined anti-zika immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay. RESULTS: ZIKV RNA was not detected in any of the 75 samples tested by real-time PCR assay. Among the voluntary blood donors and antenatal mothers, a total of 10 (15.38%) and 5 (6.66%) individuals were found to be seropositive for anti-ZIKV IgG antibodies, respectively. The seropositive group was found to have higher age 33.06 (±10.83) years as compared to seronegative individuals 26.60 (±5.12) years (P = 0.037). CONCLUSION: This study, which is the first survey of seroprevalence of anti-Zika antibodies from India, reports an overall seropositivity rate of 10% for anti-Zika antibodies among the healthy population, suggesting an ongoing, low level, silent transmission of ZIKV in the local community.


Subject(s)
Zika Virus Infection , Zika Virus , Humans , India/epidemiology , Zika Virus Infection/epidemiology , Zika Virus Infection/transmission , Seroepidemiologic Studies , Adult , Female , Pilot Projects , Male , Zika Virus/immunology , Zika Virus/isolation & purification , Immunoglobulin G/blood , Young Adult , Antibodies, Viral/blood , Middle Aged , RNA, Viral , Adolescent , Enzyme-Linked Immunosorbent Assay , Real-Time Polymerase Chain Reaction
3.
Viruses ; 16(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38932129

ABSTRACT

The complete lack of yellow fever virus (YFV) in Asia, and the lack of urban YFV transmission in South America, despite the abundance of the peridomestic mosquito vector Aedes (Stegomyia.) aegypti is an enigma. An immunologically naïve population of over 2 billion resides in Asia, with most regions infested with the urban YF vector. One hypothesis for the lack of Asian YF, and absence of urban YF in the Americas for over 80 years, is that prior immunity to related flaviviruses like dengue (DENV) or Zika virus (ZIKV) modulates YFV infection and transmission dynamics. Here we utilized an interferon α/ß receptor knock-out mouse model to determine the role of pre-existing dengue-2 (DENV-2) and Zika virus (ZIKV) immunity in YF virus infection, and to determine mechanisms of cross-protection. We utilized African and Brazilian YF strains and found that DENV-2 and ZIKV immunity significantly suppresses YFV viremia in mice, but may or may not protect relative to disease outcomes. Cross-protection appears to be mediated mainly by humoral immune responses. These studies underscore the importance of re-assessing the risks associated with YF outbreak while accounting for prior immunity from flaviviruses that are endemic.


Subject(s)
Cross Protection , Dengue Virus , Disease Models, Animal , Mice, Knockout , Receptor, Interferon alpha-beta , Yellow Fever , Yellow fever virus , Zika Virus Infection , Zika Virus , Animals , Yellow Fever/immunology , Yellow Fever/prevention & control , Yellow Fever/virology , Mice , Cross Protection/immunology , Yellow fever virus/immunology , Zika Virus/immunology , Zika Virus Infection/immunology , Zika Virus Infection/prevention & control , Zika Virus Infection/virology , Dengue Virus/immunology , Receptor, Interferon alpha-beta/genetics , Receptor, Interferon alpha-beta/deficiency , Antibodies, Viral/immunology , Antibodies, Viral/blood , Flavivirus/immunology , Aedes/virology , Aedes/immunology , Dengue/immunology , Dengue/prevention & control , Dengue/virology , Female , Viremia/immunology , Mosquito Vectors/virology , Mosquito Vectors/immunology , Flavivirus Infections/immunology , Flavivirus Infections/prevention & control , Flavivirus Infections/virology , Mice, Inbred C57BL
4.
Viruses ; 16(6)2024 May 28.
Article in English | MEDLINE | ID: mdl-38932158

ABSTRACT

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of -19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.


Subject(s)
Administration, Intranasal , Antibodies, Viral , Viral Vaccines , Zika Virus Infection , Zika Virus , Animals , Zika Virus Infection/prevention & control , Zika Virus Infection/immunology , Zika Virus/immunology , Mice , Antibodies, Viral/blood , Antibodies, Viral/immunology , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Female , Immunization/methods , Adjuvants, Immunologic/administration & dosage , Disease Models, Animal , Adjuvants, Vaccine/administration & dosage , Vaccination/methods , Cytokines/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology
5.
Am J Trop Med Hyg ; 111(1): 107-112, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38834052

ABSTRACT

Diagnostics for febrile illnesses other than malaria are not readily available in rural sub-Saharan Africa. This study assessed exposure to three mosquito-borne arboviruses-dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV)-in southern Mali. Seroprevalence for DENV, CHIKV, and ZIKV was analyzed by detection of IgG antibodies and determined to be 77.2%, 31.2%, and 25.8%, respectively. Among study participants, 11.3% were IgG-positive for all three arboviruses. DENV had the highest seroprevalence rate at all sites; the highest seroprevalence of CHIKV and ZIKV was observed in Bamba. The seroprevalence for all three arboviruses increased with age, and the highest seroprevalence was observed among adults older than 50 years. The prevalence of Plasmodium spp. in the cohort was analyzed by microscopy and determined to be 44.5% (N = 600) with Plasmodium falciparum representing 95.1% of all infections. This study demonstrates the co-circulation of arboviruses in a region hyperendemic for malaria and highlights the needs for arbovirus diagnostics in rural sub-Saharan Africa.


Subject(s)
Chikungunya Fever , Dengue Virus , Humans , Mali/epidemiology , Seroepidemiologic Studies , Adult , Middle Aged , Male , Female , Adolescent , Young Adult , Chikungunya Fever/epidemiology , Chikungunya Fever/blood , Dengue Virus/immunology , Child , Child, Preschool , Chikungunya virus/immunology , Dengue/epidemiology , Arboviruses/immunology , Arboviruses/isolation & purification , Antibodies, Viral/blood , Malaria/epidemiology , Arbovirus Infections/epidemiology , Arbovirus Infections/virology , Zika Virus Infection/epidemiology , Zika Virus Infection/blood , Zika Virus Infection/diagnosis , Zika Virus/immunology , Endemic Diseases , Immunoglobulin G/blood , Aged , Infant , Prevalence
6.
Antiviral Res ; 227: 105915, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38777094

ABSTRACT

The genus of flavivirus includes many mosquito-borne human pathogens, such as Zika (ZIKV) and the four serotypes of dengue (DENV1-4) viruses, that affect billions of people as evidenced by epidemics and endemicity in many countries and regions in the world. Among the 10 viral proteins encoded by the viral genome, the nonstructural protein 1 (NS1) is the only secreted protein and has been used as a diagnostic biomarker. NS1 has also been an attractive target for its biotherapeutic potential as a vaccine antigen. This review focuses on the recent advances in the structural landscape of the secreted NS1 (sNS1) and its complex with monoclonal antibodies (mAbs). NS1 forms an obligatory dimer, and upon secretion, it has been reported to be hexametric (trimeric dimers) that could dissociate and bind to the epithelial cell membrane. However, high-resolution structural information has been missing about the high-order oligomeric states of sNS1. Several cryoEM studies have since shown that DENV and ZIKV recombinant sNS1 (rsNS1) are in dynamic equilibrium of dimer-tetramer-hexamer states, with tetramer being the predominant form. It was recently revealed that infection-derived sNS1 (isNS1) forms a complex of the NS1 dimer partially embedded in a High-Density Lipoprotein (HDL) particle. Structures of NS1 in complexes with mAbs have also been reported which shed light on their protective roles during infection. The biological significance of the diversity of NS1 oligomeric states remains to be further studied, to inform future research on flaviviral pathogenesis and the development of therapeutics and vaccines. Given the polymorphism of flavivirus NS1 across sample types with variations in antigenicity, we propose a nomenclature to accurately define NS1 based on the localization and origin.


Subject(s)
Antibodies, Monoclonal , Antibodies, Viral , Flavivirus , Viral Nonstructural Proteins , Viral Nonstructural Proteins/immunology , Viral Nonstructural Proteins/chemistry , Viral Nonstructural Proteins/genetics , Humans , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/chemistry , Antibodies, Viral/immunology , Flavivirus/immunology , Flavivirus/chemistry , Flavivirus/genetics , Animals , Zika Virus/immunology , Zika Virus/genetics , Zika Virus/chemistry , Dengue Virus/immunology , Dengue Virus/genetics , Dengue Virus/chemistry , Protein Multimerization , Protein Conformation
7.
Sci Transl Med ; 16(749): eadn2199, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38809964

ABSTRACT

Infection with any of the four dengue virus serotypes (DENV1-4) can protect against or enhance subsequent dengue depending on preexisting antibodies and infecting serotype. Additionally, primary infection with the related flavivirus Zika virus (ZIKV) is associated with increased risk of DENV2 disease. Here, we measured how prior DENV and ZIKV immunity influenced risk of disease caused by DENV1-4 in a pediatric Nicaraguan cohort. Of 3412 participants in 2022, 10.6% experienced dengue cases caused by DENV1 (n = 139), DENV4 (n = 133), DENV3 (n = 54), DENV2 (n = 9), or an undetermined serotype (n = 39). Longitudinal clinical and serological data were used to define infection histories, and generalized linear and additive models adjusted for age, sex, time since last infection, and year, and repeat measurements were used to predict disease risk. Compared with flavivirus-naïve participants, primary ZIKV infection was associated with increased risk of disease caused by DENV4 (relative risk = 2.62, 95% confidence interval: 1.48 to 4.63) and DENV3 (2.90, 1.34 to 6.27), but not DENV1 infection. Primary DENV infection or DENV followed by ZIKV infection was also associated with increased risk of DENV4 disease. We reanalyzed 19 years of cohort data and demonstrated that prior flavivirus immunity and antibody titer had distinct associations with disease risk depending on incoming serotype. We thus find that prior ZIKV infection, like prior DENV infection, is associated with increased risk of disease with certain DENV serotypes. Cross-reactivity among flaviviruses should be considered when assessing vaccine safety and efficacy.


Subject(s)
Dengue Virus , Dengue , Serogroup , Zika Virus Infection , Zika Virus , Humans , Zika Virus/immunology , Dengue/immunology , Dengue/virology , Dengue Virus/immunology , Zika Virus Infection/immunology , Zika Virus Infection/virology , Child , Female , Male , Nicaragua/epidemiology , Child, Preschool , Risk Factors , Adolescent , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cohort Studies
8.
Vaccine ; 42(17): 3674-3683, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38749821

ABSTRACT

The Zika virus (ZIKV) is considered a public health problem worldwide due to its association with the development of microcephaly and the Guillain-Barré syndrome. Currently, there is no specific treatment or vaccine approved to combat this disease, and thus, developing safe and effective vaccines is a relevant goal. In this study, a multi-epitope protein called rpZDIII was designed based on a series of ZIKV antigenic sequences, a bacterial carrier, and linkers. The analysis of the predicted 3D structure of the rpZDIII chimeric antigen was performed on the AlphaFold 2 server, and it was produced in E. coli and purified from inclusion bodies, followed by solubilization and refolding processes. The yield achieved for rpZDIII was 11 mg/L in terms of pure soluble recombinant protein per liter of fermentation. rpZDIII was deemed immunogenic since it induced serum IgG and IgM responses in mice upon subcutaneous immunization in a three-dose scheme. Moreover, sera from mice immunized with rpZDIII showed neutralizing activity against ZIKV. Therefore, this study reveals rpZDIII as a promising immunogen for the development of a rationally designed multi-epitope vaccine against ZIKV, and completion of its preclinical evaluation is guaranteed.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Antigens, Viral , Zika Virus Infection , Zika Virus , Animals , Zika Virus/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Mice , Antibodies, Viral/immunology , Antibodies, Viral/blood , Zika Virus Infection/prevention & control , Zika Virus Infection/immunology , Antigens, Viral/immunology , Antigens, Viral/genetics , Viral Vaccines/immunology , Viral Vaccines/administration & dosage , Epitopes/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Female , Escherichia coli/genetics , Escherichia coli/metabolism , Immunoglobulin M/immunology , Immunoglobulin M/blood , Mice, Inbred BALB C
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(5): 447-454, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38790101

ABSTRACT

Objective To prepare monoclonal antibodies against the envelope protein extracellular domain (Eecto) of Zika virus (ZIKV) in mice. Methods A prokaryotic expression plasmid, pET28a-ZIKV-Eecto of ZIKV Eecto, was constructed, transformed into Escherichia coli BL21 and induced by isopropyl ß-D-thiogalactoside (IPTG). The recombinant Eecto protein was expressed in the form of inclusion bodies, and purified proteins were obtained through denaturation, renaturation and ultrafiltration. After three rounds of immunization with the Eecto protein, the serum of BALB/c mice was obtained and the titer of polyclonal antibodies in serum was determined. The reactivity of polyclonal antibodies was analyzed with Western blotting and immunofluorescence assay in HEK293T cells expressing the ZIKV prME. Spleen cells from mice with higher antibody titers were prepared and fused with SP2/0 myeloma cells. The hybridoma cells secreting antibodies were screened through the limited dilution method, and the ascites containing antibody were harvested for titer measurement and subclass analysis. The Eecto from the envelope proteins of Japanese encephalitis virus (JEV), Yellow fever virus (YFV), Dengue virus (DENV1-4), and Tick borne encephalitis virus (TBEV) were coated and used to analyze the cross-reactivity of ZIKV monoclonal antibodies by ELISA. Further specificity analysis was conducted on antibodies with high titers and strong specificity. Results The plasmid pET28a-ZIKV-Eecto was successfully constructed. The purified Eecto protein was obtained with good immunogenicity. Four monoclonal antibodies were prepared and screened, namely 1D6, 4F11, 4H7, and 4F8. Among them, 1D6, 4H7, and 4F8 are IgG (K) type antibodies, and 4F11 is an IgM (K) antibody. The ascitic fluid titer of 1D6 was higher than 1:108. Antibodies 1D6 and 4H7 are ZIKV-specific and showed no cross-reactivity with other Flaviviruses. Conclusion The mice monoclonal antibodies against ZIKV-Eecto are produced successfully, which will provide experimental materials for the establishment of ZIKV detection methods and the study of its pathogenesis.


Subject(s)
Antibodies, Monoclonal , Mice, Inbred BALB C , Viral Envelope Proteins , Zika Virus , Animals , Zika Virus/immunology , Zika Virus/genetics , Antibodies, Monoclonal/immunology , Viral Envelope Proteins/immunology , Viral Envelope Proteins/genetics , Mice , Humans , HEK293 Cells , Female , Antibodies, Viral/immunology , Protein Domains/immunology , Enzyme-Linked Immunosorbent Assay
10.
Talanta ; 276: 126215, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38723474

ABSTRACT

Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10-8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10-6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.


Subject(s)
Bacillus subtilis , Gold , Limit of Detection , Metal Nanoparticles , Bacillus subtilis/immunology , Immunoassay/methods , Gold/chemistry , Metal Nanoparticles/chemistry , Humans , Spores, Bacterial/immunology , SARS-CoV-2/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Zika Virus/immunology
11.
Viruses ; 16(5)2024 05 19.
Article in English | MEDLINE | ID: mdl-38793688

ABSTRACT

Arboviral diseases are serious threats to global health with increasing prevalence and potentially severe complications. Significant arthropod-borne viruses are the dengue viruses (DENV 1-4), the Zika virus (ZIKV), and the chikungunya virus (CHIKV). Among the areas most affected is the South Pacific Region (SPR). Here, arboviruses not only cause a high local burden of disease, but the region has also proven to contribute to their global spread. Outpatient serum samples collected between 08/2016 and 04/2017 on three islands of the island states of Vanuatu and the Cook Islands were tested for anti-DENV- and anti-ZIKV-specific antibodies (IgG) using enzyme-linked immunosorbent assays (ELISA). ELISA test results showed 89% of all test sera from the Cook Islands and 85% of the Vanuatu samples to be positive for anti-DENV-specific antibodies. Anti-ZIKV antibodies were identified in 66% and 52%, respectively, of the test populations. Statistically significant differences in standardized immunity levels were found only at the intranational level. Our results show that in both the Cook Islands and Vanuatu, residents were exposed to significant Flavivirus transmission. Compared to other seroprevalence studies, the marked difference between ZIKV immunity levels and previously published CHIKV seroprevalence rates in our study populations is surprising. We propose the timing of ZIKV and CHIKV emergence in relation to recurrent DENV outbreaks and the impact of seasonality as explanatory external factors for this observation. Our data add to the knowledge of arboviral epidemics in the SPR and contribute to a better understanding of virus spread, including external conditions with potential influence on outbreak dynamics. These data may support preventive and rapid response measures in the affected areas, travel-related risk assessment, and infection identification in locals and returning travelers.


Subject(s)
Antibodies, Viral , Dengue Virus , Dengue , Zika Virus Infection , Zika Virus , Humans , Zika Virus Infection/epidemiology , Zika Virus Infection/blood , Zika Virus Infection/immunology , Zika Virus Infection/virology , Seroepidemiologic Studies , Dengue Virus/immunology , Zika Virus/immunology , Vanuatu/epidemiology , Dengue/epidemiology , Dengue/immunology , Dengue/blood , Dengue/virology , Polynesia/epidemiology , Antibodies, Viral/blood , Adult , Female , Adolescent , Young Adult , Male , Middle Aged , Aged , Child , Enzyme-Linked Immunosorbent Assay , Child, Preschool , Immunoglobulin G/blood , Infant
12.
PLoS One ; 19(5): e0302684, 2024.
Article in English | MEDLINE | ID: mdl-38722858

ABSTRACT

BACKGROUND: In most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection. AIM: To test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection. METHODS: A comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay. RESULTS: Circulating CD4+ and CD8+ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4+ and CD8+ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4+ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein. CONCLUSION: Circulating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.


Subject(s)
CD8-Positive T-Lymphocytes , Interferon-gamma , Zika Virus Infection , Zika Virus , Humans , Zika Virus Infection/immunology , Zika Virus Infection/epidemiology , Adult , Zika Virus/immunology , Female , Male , Interferon-gamma/metabolism , Interferon-gamma/immunology , Brazil/epidemiology , CD8-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Middle Aged , Young Adult , Epidemics , Lymphocyte Activation/immunology , T-Lymphocytes/immunology
13.
Proc Natl Acad Sci U S A ; 121(21): e2312755121, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38743628

ABSTRACT

Antigenic similarities between Zika virus (ZIKV) and other flaviviruses pose challenges to the development of virus-specific diagnostic tools and effective vaccines. Starting with a DNA-encoded one-bead-one-compound combinatorial library of 508,032 synthetic, non-natural oligomers, we selected and characterized small molecules that mimic ZIKV epitopes. High-throughput fluorescence-activated cell sorter-based bead screening was used to select molecules that bound IgG from ZIKV-immune but not from dengue-immune sera. Deep sequencing of the DNA from the "Zika-only" beads identified 40 candidate molecular structures. A lead candidate small molecule "CZV1-1" was selected that correctly identifies serum specimens from Zika-experienced patients with good sensitivity and specificity (85.3% and 98.4%, respectively). Binding competition studies of purified anti-CZV1-1 IgG against known ZIKV-specific monoclonal antibodies (mAbs) showed that CZV1-1 mimics a nonlinear, neutralizing conformational epitope in the domain III of the ZIKV envelope. Purified anti-CZV1-1 IgG neutralized infection of ZIKV in cell cultures with potencies comparable to highly specific ZIKV-neutralizing mAbs. This study demonstrates an innovative approach for identification of synthetic non-natural molecular mimics of conformational virus epitopes. Such molecular mimics may have value in the development of accurate diagnostic assays for Zika, as well as for other viruses.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Zika Virus Infection , Zika Virus , Zika Virus/immunology , Epitopes/immunology , Humans , Zika Virus Infection/immunology , Zika Virus Infection/virology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Immunoglobulin G/immunology , Antibodies, Monoclonal/immunology , Molecular Mimicry/immunology
14.
Am J Trop Med Hyg ; 110(6): 1178-1179, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38653230

ABSTRACT

We report strong Zika virus (ZIKV) neutralizing antibody responses in African green monkeys (Chlorocebus sabaeus) up to 1,427 days after ZIKV exposure via the subcutaneous, intravaginal, or intrarectal routes. Our results suggest that immunocompetent African green monkeys previously infected with ZIKV are likely protected from reinfection for years, possibly life, and would not contribute to virus amplification during ZIKV epizootics.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , Zika Virus Infection , Zika Virus , Animals , Chlorocebus aethiops , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Zika Virus/immunology , Zika Virus Infection/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Female
15.
Biologicals ; 86: 101765, 2024 May.
Article in English | MEDLINE | ID: mdl-38593685

ABSTRACT

Yellow fever (YF) is one of the most acute viral hemorrhagic diseases of the 18th and 19th centuries, which continues to cause severe morbidity and mortality in Africa. After 21 years of no reported cases of yellow fever in Nigeria, till 2017 where a case was confirmed in Kwara State, also in November 2018,WHO was informed of a cluster of suspected yellow fever cases and deaths in Edo state, Nigeria. The study was among all age group attending health centres in Benin City, Edo state. A total of 280 blood samples were collected from consented febrile patients and were screened for antibodies to Zika virus using rapid diagnostic test (RDT) kits. Blood samples positive to Zika virus (IgM/IgG RDT), were subjected to molecular characterization. Using the flavividae family primers, six (6) samples where confirmed positive by Hemi-nested reverse transcription PCR (hnRT-PCR) sequencing. Nucleotide sequence blast revealed the sequenceswere similar to Yellow fever virus strains. Phylogenetic analysis revealed that the yellow fever virus sequences are closely related to the African strains. Despite the safe and effective yellow fever vaccine, yellow fever virus is seen to be in circulation, hence the need for continues mass vaccination.


Subject(s)
Phylogeny , Yellow Fever , Yellow fever virus , Humans , Nigeria/epidemiology , Yellow fever virus/genetics , Yellow fever virus/immunology , Yellow Fever/epidemiology , Yellow Fever/virology , Yellow Fever/blood , Adult , Female , Male , Adolescent , Middle Aged , Child , Child, Preschool , Young Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Infant , Zika Virus/genetics , Zika Virus/immunology , Zika Virus/isolation & purification
16.
Microbiol Spectr ; 12(6): e0075824, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38687079

ABSTRACT

Human immunoglobulin preparations contain a diverse range of polyclonal antibodies that reflect past immune responses against pathogens encountered by the blood donor population. In this study, we examined a panel of intravenous immunoglobulins (IGIVs) manufactured over the past two decades (1998-2020) for their capacity to neutralize or enhance Zika virus (ZIKV) infection in vitro. These IGIVs were selected specifically based on their production dates in relation to the occurrences of two flavivirus outbreaks in the U.S.: the West Nile virus (WNV) outbreak in 1999 and the ZIKV outbreak in 2015. As demonstrated by enzyme-linked immunosorbent assay (ELISA) experiments, IGIVs made before the ZIKV outbreak already harbored antibodies that bind to various peptides across the envelope protein of ZIKV because of the WNV outbreak. Using phage display, the most dominant binding site was mapped precisely to the P2 peptide between residues 211 and 230 within domain II, where BF1176-56, an anti-ZIKV monoclonal antibody, also binds. When tested in permissive Vero E6 cells for ZIKV neutralization, the IGIVs, even after undergoing rigorous enrichment for P2 binding specificity, failed, as did BF1176-56. Meanwhile, BF1176-56 enhanced ZIKV infection in both FcγRII-expressing K562 cells and human peripheral blood mononuclear cells. However, for enhancement by the IGIVs to be detected in these cells, a substantial increase in their P2 binding specificity was required, thus linking the P2 site with ZIKV enhancement in vitro. Our findings warrant further study of the significance of elevated levels of anti-WNV antibodies in IGIVs, considering that various mechanisms operating in vivo may modulate ZIKV infection outcomes.IMPORTANCEWe investigated the capacity of intravenous immunoglobulins manufactured previously over two decades (1998-2020) to neutralize or enhance Zika virus infection in vitro. West Nile virus antibodies in IGIVs could not neutralize Zika virus initially; however, once the IGIVs were concentrated further, they enhanced its infection. These findings lay the groundwork for exploring how preexisting WNV antibodies in IGIVs could impact Zika infection, both in vitro and in vivo. Our observations are historically significant, since we tested a panel of IGIV lots that were carefully selected based on their production dates which covered two major flavivirus outbreaks in the U.S.: the WNV outbreak in 1999 and the ZIKV outbreak in 2015. These findings will facilitate our understanding of the interplay among closely related viral pathogens, particularly from a historical perspective regarding large blood donor populations. They should remain relevant for future outbreaks of emerging flaviviruses that may potentially affect vulnerable populations.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , West Nile Fever , West Nile virus , Zika Virus Infection , Zika Virus , Humans , Zika Virus/immunology , West Nile virus/immunology , Antibodies, Viral/immunology , Zika Virus Infection/immunology , Zika Virus Infection/virology , Animals , Chlorocebus aethiops , Vero Cells , West Nile Fever/immunology , West Nile Fever/virology , Antibodies, Neutralizing/immunology , Binding Sites , Immunoglobulins, Intravenous/immunology , Viral Envelope Proteins/immunology , Enzyme-Linked Immunosorbent Assay
17.
Emerg Microbes Infect ; 13(1): 2348528, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38662785

ABSTRACT

Zika is a systemic inflammatory disease caused by infection with Zika virus (ZIKV). ZIKV infection in adults is associated with encephalitis marked by elevated expression of pro-inflammatory cytokines and chemokines, as well as increased brain infiltration of immune cells. In this study, we demonstrate that ZIKV encephalitis in a mouse infection model exhibits increased brain TSPO expression. TSPO expression on brain-resident and infiltrating immune cells in ZIKV infection correlates with disease and inflammation status in the brain. Brain TSPO expression can also be sensitively detected ex vivo and in vitro using radioactive small molecule probes that specifically bind to TSPO, such as [3H]PK11195. TSPO expression on brain-resident and infiltrating immune cells is a biomarker of ZIKV neuroinflammation, which can also be a general biomarker of acute viral neuroinflammatory disease.


Subject(s)
Biomarkers , Brain , Neuroinflammatory Diseases , Receptors, GABA , Zika Virus Infection , Zika Virus , Animals , Zika Virus Infection/virology , Zika Virus Infection/immunology , Zika Virus Infection/metabolism , Mice , Receptors, GABA/metabolism , Receptors, GABA/genetics , Zika Virus/immunology , Brain/virology , Brain/metabolism , Brain/pathology , Neuroinflammatory Diseases/virology , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/metabolism , Disease Models, Animal , Humans , Mice, Inbred C57BL , Female , Cytokines/metabolism
18.
Virus Res ; 345: 199376, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38643856

ABSTRACT

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are antigenically related flaviviruses that co-circulate in many countries/territories. The interaction between the two viruses needs to be determined. Recent findings by ourselves and other labs showed that JEV-elicited antibodies (Abs) and CD8+T cells exacerbate and protect against subsequent ZIKV infection, respectively. However, the impact of JEV envelope (E) protein domain III (EDIII)-induced immune responses on ZIKV infection is unclear. We show here that sera from JEV-EDIII-vaccinated mice cross-react with ZIKV-EDIII in vitro, and transfer of the same sera to mice significantly decreases death upon lethal ZIKV infection at a dose-dependent manner. Maternally acquired anti-JEV-EDIII Abs also significantly reduce the mortality of neonatal mice born to JEV-EDIII-immune mothers post ZIKV challenge. Similarly, transfer of ZIKV-EDIII-reactive IgG purified from JEV-vaccinated humans increases the survival of ZIKV-infected mice. Notably, transfer of an extremely low volume of JEV-EDIII-immune sera or ZIKV-EDIII-reactive IgG does not mediate the Ab-mediated enhancement (ADE) of ZIKV infection. Similarly, transfer of JEV-EDIII-elicited CD8+T cells protects recipient mice against ZIKV challenge. These results demonstrate that JEV-EDIII-induced immune components including Abs and T cells have protective roles in ZIKV infection, suggesting EDIII is a promising immunogen for developing effective and safety JEV vaccine.


Subject(s)
Antibodies, Viral , CD8-Positive T-Lymphocytes , Cross Protection , Encephalitis Virus, Japanese , Viral Envelope Proteins , Zika Virus Infection , Zika Virus , Animals , Zika Virus Infection/prevention & control , Zika Virus Infection/immunology , CD8-Positive T-Lymphocytes/immunology , Zika Virus/immunology , Antibodies, Viral/immunology , Antibodies, Viral/blood , Viral Envelope Proteins/immunology , Mice , Encephalitis Virus, Japanese/immunology , Cross Protection/immunology , Female , Cross Reactions , Encephalitis, Japanese/prevention & control , Encephalitis, Japanese/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin G/blood , Disease Models, Animal , Immunization
19.
PLoS Negl Trop Dis ; 18(4): e0011842, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38630843

ABSTRACT

BACKGROUND: Zika virus (ZIKV) has spread to five of the six World Health Organization (WHO) regions. Given the substantial number of asymptomatic infections and clinical presentations resembling those of other arboviruses, estimating the true burden of ZIKV infections is both challenging and essential. Therefore, we conducted a systematic review and meta-analysis of seroprevalence studies of ZIKV IgG in asymptomatic population to estimate its global impact and distribution. METHODOLOGY/PRINCIPAL FINDINGS: We conducted extensive searches and compiled a collection of articles published from Jan/01/2000, to Jul/31/2023, from Embase, Pubmed, SciELO, and Scopus databases. The random effects model was used to pool prevalences, reported with their 95% confidence interval (CI), a tool to assess the risk of study bias in prevalence studies, and the I2 method for heterogeneity (PROSPERO registration No. CRD42023442227). Eighty-four studies from 49 countries/territories, with a diversity of study designs and serological tests were included. The global seroprevalence of ZIKV was 21.0% (95%CI 16.1%-26.4%). Evidence of IgG antibodies was identified in all WHO regions, except for Europe. Seroprevalence correlated with the epidemics in the Americas (39.9%, 95%CI:30.0-49.9), and in some Western Pacific countries (15.6%, 95%CI:8.2-24.9), as well as with recent and past circulation in Southeast Asia (22.8%, 95%CI:16.5-29.7), particularly in Thailand. Additionally, sustained low circulation was observed in Africa (8.4%, 95%CI:4.8-12.9), except for Gabon (43.7%), and Burkina Faso (22.8%). Although no autochthonous transmission was identified in the Eastern Mediterranean, a seroprevalence of 16.0% was recorded. CONCLUSIONS/SIGNIFICANCE: The study highlights the high heterogeneity and gaps in the distribution of seroprevalence. The implementation of standardized protocols and the development of tests with high specificity are essential for ensuring a valid comparison between studies. Equally crucial are vector surveillance and control methods to reduce the risk of emerging and re-emerging ZIKV outbreaks, whether caused by Ae. aegypti or Ae. albopictus or by the Asian or African ZIKV.


Subject(s)
Antibodies, Viral , Zika Virus Infection , Zika Virus , Humans , Seroepidemiologic Studies , Zika Virus Infection/epidemiology , Zika Virus/immunology , Antibodies, Viral/blood , Immunoglobulin G/blood , Global Health , Asymptomatic Infections/epidemiology
20.
Braz J Infect Dis ; 28(2): 103741, 2024.
Article in English | MEDLINE | ID: mdl-38670165

ABSTRACT

Sickle Cell Disease (SCD) is a hereditary disease characterized by extravascular and intravascular hemolysis and clinical variability, from mild pain to potentially life-threatening. Arboviruses include mainly Zika (ZIKV), Chikungunya (CHKV), and Dengue (DENV) virus, and are considered a public and social health problem. The present cross-sectional observational study aimed to investigate the prevalence of arbovirus infection in SCD patients from two Brazilian cities, Salvador and Manaus located in Bahia and Amazonas states respectively. A total of 409 individuals with SCD were included in the study, and 307 (75.06 %) patients tested positive for DENV-IgG, 161 (39.36 %) for ZIKV-IgG, and 60 (14.67 %) for CHIKV-IgG. Only one individual was positive for DENV-NS1 and another for DENV-IgM, both from Salvador. No individuals had positive serology for ZIKV-IgM or CHIKV-IgM. Arbovirus positivity by IgG testing revealed that the SCD group presented high frequencies in both cities. Interestingly, these differences were only statistically significant for ZIKV-IgG (p = 0.023) and CHIKV-IgG (p = 0.005) among SCD patients from Manaus. The reshaping of arbovirus from its natural habitat by humans due to disorderly urban expansion and the ease of international Mobility has been responsible for facilitating the spread of vector-borne infectious diseases in humans. We found the need for further studies on arboviruses in this population to elucidate the real association and impact, especially in acute infection. We hope that this study will contribute to improvements in the personalized clinical follow-up of SCD patients, identifying the influence of arbovirus infection in severe disease manifestations.


Subject(s)
Anemia, Sickle Cell , Arbovirus Infections , Arboviruses , Humans , Brazil/epidemiology , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/complications , Cross-Sectional Studies , Male , Female , Adult , Prevalence , Arbovirus Infections/epidemiology , Arbovirus Infections/virology , Young Adult , Adolescent , Arboviruses/isolation & purification , Immunoglobulin G/blood , Child , Zika Virus Infection/epidemiology , Zika Virus Infection/complications , Antibodies, Viral/blood , Middle Aged , Dengue/epidemiology , Immunoglobulin M/blood , Dengue Virus/immunology , Zika Virus/immunology , Zika Virus/isolation & purification , Child, Preschool , Chikungunya Fever/epidemiology , Chikungunya Fever/complications
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