scholarly journals Human dengue virus serotype 2 neutralizing antibodies target two distinct quaternary epitopes

2018 ◽  
Vol 14 (2) ◽  
pp. e1006934 ◽  
Author(s):  
Emily N. Gallichotte ◽  
Thomas J. Baric ◽  
Boyd L. Yount ◽  
Douglas G. Widman ◽  
Anna Durbin ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2

scholarly journals The Chimeric Protein Domain III-Capsid of Dengue Virus Serotype 2 (DEN-2) Successfully Boosts Neutralizing Antibodies Generated in Monkeys upon Infection with DEN-2

2011 ◽  
Vol 18 (3) ◽  
pp. 455-459 ◽  
Author(s):  
Iris Valdés ◽  
Lázaro Gil ◽  
Yaremis Romero ◽  
Jorge Castro ◽  
Pedro Puente ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Chimeric Protein ◽  
Neutralizing Antibody ◽  
Protein Domain ◽  
Homologous Virus ◽  
Virus Serotype ◽  
Attenuated Virus ◽  
Domain Iii ◽  
Dengue Virus Serotype 2

ABSTRACTUse of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time spacing. The present work deals with the evaluation of the heterologous prime-boost strategy combining a novel chimeric protein (domain III-capsid) of dengue virus serotype 2 (DEN-2) and the infective homologous virus in the same immunization schedule in monkeys. Primed monkeys received one dose of infective DEN-2 and were then vaccinated with the recombinant protein. We found that animals developed a neutralizing antibody response after the infective dose and were notably boosted with a second dose of the chimeric protein 3 months later. The neutralizing antibodies induced were long lasting, and animals also showed the ability to induce a specific cellular response 6 months after the booster dose. As a conclusion, we can state that the domain III region, when it is properly presented as a fusion protein to the immune system, is able to recall the neutralizing antibody response elicited following homologous virus infection in monkeys. Further prime-boost approaches can be performed in a condensed regime combining the chimeric domain III-capsid protein and candidate live attenuated vaccines against DEN-2.

scholarly journals A New Quaternary Structure Epitope on Dengue Virus Serotype 2 Is the Target of Durable Type-Specific Neutralizing Antibodies

mBio ◽  
2015 ◽  
Vol 6 (5) ◽  
Author(s):  
E. N. Gallichotte ◽  
D. G. Widman ◽  
B. L. Yount ◽  
W. M. Wahala ◽  
A. Durbin ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Quaternary Structure ◽  
Natural Infection ◽  
Viral Envelope ◽  
Protective Response ◽  
Denv Serotypes ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2

ABSTRACT Dengue virus serotype 2 (DENV2) is widespread and responsible for severe epidemics. While primary DENV2 infections stimulate serotype-specific protective responses, a leading vaccine failed to induce a similar protective response. Using human monoclonal antibodies (hMAbs) isolated from dengue cases and structure-guided design of a chimeric DENV, here we describe the major site on the DENV2 envelope (E) protein targeted by neutralizing antibodies. DENV2-specific neutralizing hMAb 2D22 binds to a quaternary structure epitope. We engineered and recovered a recombinant DENV4 that displayed the 2D22 epitope. DENV2 neutralizing antibodies in people exposed to infection or a live vaccine tracked with the 2D22 epitope on the DENV4/2 chimera. The chimera remained sensitive to DENV4 antibodies, indicating that the major neutralizing epitopes on DENV2 and -4 are at different sites. The ability to transplant a complex epitope between DENV serotypes demonstrates a hitherto underappreciated structural flexibility in flaviviruses, which could be harnessed to develop new vaccines and diagnostics. IMPORTANCE Dengue virus causes fever and dengue hemorrhagic fever. Dengue serotype 2 (DENV2) is widespread and frequently responsible for severe epidemics. Natural DENV2 infections stimulate serotype-specific neutralizing antibodies, but a leading DENV vaccine did not induce a similar protective response. While groups have identified epitopes of single monoclonal antibodies (MAbs), the molecular basis of DENV2 neutralization by polyclonal human immune sera is unknown. Using a recombinant DENV displaying serotype 2 epitopes, here we map the main target of DENV2 polyclonal neutralizing antibodies induced by natural infection and a live DENV2 vaccine candidate. Proper display of the epitope required the assembly of viral envelope proteins into higher-order structures present on intact virions. Despite the complexity of the epitope, it was possible to transplant the epitope between DENV serotypes. Our findings have immediate implications for evaluating dengue vaccines in the pipeline as well as designing next-generation vaccines.

Dengue Virus Serotype-2 Interferes with the Formation of Neutrophil Extracellular Traps

Intervirology ◽  
2015 ◽  
Vol 58 (4) ◽  
pp. 250-259 ◽  
Author(s):  
Maria Maximina B. Moreno-Altamirano ◽  
Oscar Rodríguez-Espinosa ◽  
Oscar Rojas-Espinosa ◽  
Bernardo Pliego-Rivero ◽  
Francisco J. Sánchez-García
Keyword(s):  
Dengue Virus ◽  
Neutrophil Extracellular Traps ◽  
Extracellular Traps ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2

Impact of Dengue Virus Serotype 2 Strain Diversity on Serological Immune Responses to Dengue

2018 ◽  
Vol 4 (12) ◽  
pp. 1705-1717 ◽  
Author(s):  
Sarah L. Keasey ◽  
Jessica L. Smith ◽  
Stefan Fernandez ◽  
Anna P. Durbin ◽  
Bryan M. Zhao ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Strain Diversity ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2

scholarly journals Expression of Recombinant Non Structural 1 Protein of Dengue Virus Serotype-2 in Mammalian Cell Line

2019 ◽  
Vol 13 (1) ◽  
pp. 36-42 ◽  
Author(s):  
FITHRIYAH SJATHA ◽  
◽  
OKTIVIA CHANDRA MUSTIKA ◽  
ANGKY BUDIANTI ◽  
TJAHJANI MIRAWATI SUDIRO ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Cell Line ◽  
Mammalian Cell ◽  
Mammalian Cell Line ◽  
Virus Serotype ◽  
Dengue Virus Serotype 2

scholarly journals Subversion of immunoproteasome subunit expression in dengue virus serotype 2-infected HepG2 cells

2017 ◽  
Vol 50 (1) ◽  
pp. 99-103
Author(s):  
Chye Sheng Gan ◽  
Pei Jean Lim ◽  
Muhammad Fazril Mohamad Razif ◽  
Rohana Yusof ◽  
Shatrah Othman
Keyword(s):  
Dengue Virus ◽  
Hepg2 Cells ◽  
Virus Serotype ◽  
Subunit Expression ◽  
Dengue Virus Serotype 2

Peptides P4 and P7 derived from E protein inhibit entry of dengue virus serotype 2 via interacting with β3 integrin

2018 ◽  
Vol 155 ◽  
pp. 20-27 ◽  
Author(s):  
Xiaoyun Cui ◽  
Yanhua Wu ◽  
Dongying Fan ◽  
Na Gao ◽  
Ying Ming ◽  
...  
Keyword(s):  
Dengue Virus ◽  
E Protein ◽  
Virus Serotype ◽  
Β3 Integrin ◽  
Dengue Virus Serotype 2
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