Human Dengue Antibodies against Structural and Nonstructural Proteins

Valdés, Katia; Álvarez, Mayling; Pupo, Maritza; Vázquez, Susana; Rodriguez, Rayner; Guzmán, María G.

doi:10.1128/cdli.7.5.856-857.2000

Cited by 97 publications

(81 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, heat denaturation of the protein significantly reduced the reaction of the protein with the tested human sera, which indicates that the recombinant protein maintains structural features of the native viral protein. Recognition of NS5 by antibodies from DENVinfected patients has been reported previously (59). Nonetheless, our results demonstrated that antibodies in DENV-infected subjects recognized both linear and conformational epitopes of the protein.…”

Section: Discussioncontrasting

confidence: 37%

Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen

Alves

Pereira

Fabris

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

Dengue fever is caused by any of the four known dengue virus serotypes (DENV1 to DENV4) that affect millions of people worldwide, causing a significant number of deaths. There are vaccines based on chimeric viruses, but they still are not in clinical use. Anti-DENV vaccine strategies based on nonstructural proteins are promising alternatives to those based on whole virus or structural proteins. The DENV nonstructural protein 5 (NS5) is the main target of anti-DENV T cell-based immune responses in humans. In this study, we purified a soluble recombinant form of DENV2 NS5 expressed in Escherichia coli at large amounts and high purity after optimization of expression conditions and purification steps. The purified DENV2 NS5 was recognized by serum from DENV1-, DENV2-, DENV3-, or DENV4-infected patients in an epitope-conformation-dependent manner. In addition, immunization of BALB/c mice with NS5 induced high levels of NS5-specific antibodies and expansion of gamma interferon-and tumor necrosis factor alpha-producing T cells. Moreover, mice immunized with purified NS5 were partially protected from lethal challenges with the DENV2 NGC strain and with a clinical isolate (JHA1). These results indicate that the recombinant NS5 protein preserves immunological determinants of the native protein and is a promising vaccine antigen capable of inducing protective immune responses. Dengue fever is an acute disease caused by dengue virus (DENV), an arbovirus belonging to the Flaviviridae family, transmitted by Aedes mosquitoes (1, 2). In urban settings, DENV is found as four immunologically distinct types (serotypes), DENV1 to DENV4, which have approximately 30% divergence in their genomic nucleotide sequences (3-7). The disease may present with different degrees of manifestations that are classified by the WHO as dengue fever, dengue with warning signs, and severe dengue (8). A recent study showed that, annually, an average of 96 million DENV-infected people develop symptoms with severity sufficient to change their routines (1); according to previous studies, about 500,000 cases develop into severe forms of disease, which may include hemorrhage and shock syndrome (9). The mortality rate in this group reaches 10% in hospitalized patients, increasing to 30% in nontreated DENV-infected patients (9-11). Despite the high epidemiological importance of dengue fever, no effective anti-DENV drug or vaccine formulation is in clinical use for treatment or prevention of the disease.Several strategies have been explored, aiming toward the development of an effective dengue vaccine (12-21). Nonetheless, a tetravalent vaccine formulation requires a neutralizing response to all four serotypes (22)(23)(24)(25). A poor vaccine-induced response to structural proteins of any of the four serotypes may pose a risk of the onset of antibody-dependent enhancement (ADE) of virus replication upon infection by a subneutralized serotype (22-25). Moreover, protection based on the induction of neutralizing antibodies targeting structural proteins may be neg...

show abstract

Section: Discussioncontrasting

confidence: 37%

Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen

Alves

Pereira

Fabris

et al. 2016

Clin Vaccine Immunol

View full text Add to dashboard Cite

show abstract

“…The possibility of anti-NS1 antibodies resulting from a previous infection in quenching the NS1 antigen of a current infection has been discussed to explain this observation (Valdes et al 2000, Libraty et al 2002, Koraka et al 2003. Nevertheless, NS1 assay was found to have around 50% sensitivity among secondary dengue infections in Singapore, where approximately 45% of dengue cases are secondary infections (Low et al 2006).…”

Section: Ns1 Antigen Assays For Dengue Diagnostics and Surveillancementioning

confidence: 99%

Evaluation of Nonstructural 1 Antigen Assays for the Diagnosis and Surveillance of Dengue in Singapore

Pok

Lai

Sng

et al. 2010

Vector-Borne and Zoonotic Diseases

View full text Add to dashboard Cite

Early and accurate diagnosis of dengue is imperative for disease surveillance, which helps in the control of dengue in endemic countries. In this study, we evaluated the performance of three commercially available dengue nonstructural 1 (NS1) antigen assays (Bio-Rad PlateliaÔ Dengue NS1 Antigen ELISA, PanBio Dengue Early ELISA, and Bio-Rad Dengue NS1 Antigen Strip test) and compared them with reverse-transcription polymerase chain reaction (RT-PCR) and other commercially available serological assays for the diagnosis of dengue. The analysis showed RT-PCR to be the most sensitive and specific (100%) diagnostic method during the first 3 days of fever. The overall sensitivity of dengue NS1 antigen assays within the same period was 81.7%, indicating their potential role as a cost-effective and convenient alternative method to RT-PCR for the diagnosis of dengue fever in a primary healthcare setting. However, reduced sensitivity in detecting secondary dengue infections was one of the drawbacks of dengue NS1 antigen assays. Nonetheless, it remains a useful assay for the early detection of dengue and hence could play an important role in routine surveillance efforts to control dengue outbreaks in Singapore.

show abstract

“…Recent studies indicate that anti-NS1 and -NS3 antibodies are detected mainly in secondary infections while those anti-E and anti-NS3 antibodies are detected in both primary and secondary infections (Valdés et al 2000). This fact indicates that virus proteins derived from strains of the viruses that are causing disease in a given area are more useful for dengue virus diagnostic in that endemic area.…”

mentioning

confidence: 95%

Comparative immunological recognition of proteins from New Guinea "C" dengue virus type 2 prototype and from a dengue virus type 2 strain isolated in the State of Rio de Janeiro, Brazil

Côrtes¹,

Barth²,

Pantoja³

et al. 2003

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

Human Dengue Antibodies against Structural and Nonstructural Proteins

Cited by 97 publications

References 6 publications

Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen

Production of a Recombinant Dengue Virus 2 NS5 Protein and Potential Use as a Vaccine Antigen

Evaluation of Nonstructural 1 Antigen Assays for the Diagnosis and Surveillance of Dengue in Singapore

Comparative immunological recognition of proteins from New Guinea "C" dengue virus type 2 prototype and from a dengue virus type 2 strain isolated in the State of Rio de Janeiro, Brazil

Contact Info

Product

Resources

About