Short report: Antibody responses of mice immunized with a tetravalent dengue recombinant protein subunit vaccine.

Simmons, Monika; Murphy, Gerald S.; Hayes, Curtis G.

doi:10.4269/ajtmh.2001.65.159

Cited by 75 publications

(55 citation statements)

References 19 publications

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“…Of the anti-ED3 antibodies that are strongly neutralizing, however, the majority are usually serotype specific (5,55,60), and crossreactive antibodies are generally weaker neutralizers (19,61). There have been a number of vaccination studies investigating ED3 as a potential immunogen (3,30,(57)(58)(59).…”

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confidence: 99%

An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection

Midgley

Bajwa-Joseph

Vasanawathana

et al. 2011

J Virol

183

168

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The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simple in vitro enzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.Dengue virus is an insect-borne flavivirus transmitted to humans by the bite of an infected mosquito, usually Aedes aegypti (20). There are four circulating serotypes of dengue (dengue serotype 1 [Den1] to Den4) that show up to 70% sequence homology across their genomes (4, 17), and it is common for multiple viral serotypes to cocirculate in countries where dengue is endemic. Most dengue infections are either asymptomatic or lead to uncomplicated dengue fever (DF). However, in 1 to 5% of cases, symptoms can be more severe with the development of plasma leakage and hemorrhage. Such dengue hemorrhagic fever (DHF) can lead to circulatory collapse, resulting in a mortality rate of around 20% if left untreated.The more frequent occurrence of DHF in secondary dengue infections in children and adults suggests a role for the acquired immune system in disease pathogenesis, and there has been considerable research into both the B-and T-cell responses. Antibody-dependent enhancement (ADE) of infection, proposed by Halstead in 1977 (24, 25), is one hypothesis for this increase in severity in secondary infections (23,36). During a primary infection, antibodies that cross-react with the remaining 3 serotypes are induced. After a few months, when heterologous protection is no longer observed (54), it is hypothesized that these cross-reactive antibodies decline to subneutralizing levels, meaning that a heterologous infecting serot...

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confidence: 99%

An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection

Midgley

Bajwa-Joseph

Vasanawathana

et al. 2011

J Virol

183

168

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“…By use of these antigens, typespecific antibodies were found in mouse hyperimmune sera. The investigations were continued by Simmons et al (16,17), who applied a mixture of all four recombinant dengue virus B domains to establish a dengue virus-specific enzyme-linked immunosorbent assay.…”

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confidence: 99%

“…In contrast to earlier expression strategies (4,12,16,17), our antigens consisted of B domains with His tags for improved purification. For the amplification of the respective B domain coding regions, supernatants of dengue virus serotypes 1 to 4 (9), of WN virus (Wengler strain; SwissProt accession no.…”

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confidence: 99%

Serological Differentiation of Infections with Dengue Virus Serotypes 1 to 4 by Using Recombinant Antigens

et al. 2002

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The B domains of dengue virus serotypes 1 to 4 were expressed in Escherichia coli. The purified proteins were applied to immunoblot strips to detect serotype-specific antibodies in paired serum samples from 41 patients with primary and secondary dengue infections. A close correlation between the results obtained with the immunoblot strips and by type-specific reverse transcription-PCR (T. Laue, P. Emmerich, and H. Schmitz, J. Clin. Microbiol. 37:2543-2547, 1999) was observed.

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“…MBP confers the additional benefits of enhanced stability and solubility to passenger proteins, possibly by the formation of stable sequestered intermediate fusion partners that permit proteins to eventually regain their native conformation (4). More recently, MBP was utilized as a chaperone component in various experimental subunit vaccines against pathogenic bacteria (6,9) and viruses (3,(15)(16)(17). The enhanced immunogenicity of recombinant protein-MBP vaccines has been demonstrated in animal models against pathogens such as dengue virus (15,16) and Plasmodium falciparum (7).…”

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confidence: 99%

Potential Role for Toll-Like Receptor 4 in Mediating Escherichia coli Maltose-Binding Protein Activation of Dendritic Cells

Fernandez¹,

Palmer²,

Simmons

et al. 2007

Infect Immun

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The Escherichia coli maltose-binding protein (MBP) is used to increase the stability and solubility of proteins in bacterial protein expression systems and is increasingly being used to facilitate the production and delivery of subunit vaccines against various pathogenic bacteria and viruses. The MBP tag is presumed inert, with minimum effects on the bioactivity of the tagged protein or its biodistribution.

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Short report: Antibody responses of mice immunized with a tetravalent dengue recombinant protein subunit vaccine.

Cited by 75 publications

References 19 publications

An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection

An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection

Serological Differentiation of Infections with Dengue Virus Serotypes 1 to 4 by Using Recombinant Antigens

Potential Role for Toll-Like Receptor 4 in Mediating Escherichia coli Maltose-Binding Protein Activation of Dendritic Cells

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