An adenovirus prime-plasmid boost strategy for induction of equipotent immune responses to two dengue virus serotypesReport as inadecuate




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BMC Biotechnology

, 7:10

First Online: 15 February 2007Received: 23 August 2006Accepted: 15 February 2007

Abstract

BackgroundDengue is a public health problem of global significance for which there is neither an effective antiviral therapy nor a preventive vaccine. It is a mosquito-borne viral disease, caused by dengue DEN viruses, which are members of the Flaviviridae family. There are four closely related serotypes, DEN-1, DEN-2, DEN-3 and DEN-4, each of which is capable of causing disease. As immunity to any one serotype can potentially sensitize an individual to severe disease during exposure to a heterologous serotype, the general consensus is that an effective vaccine should be tetravalent, that is, it must be capable of affording protection against all four serotypes. The current strategy of creating tetravalent vaccine formulations by mixing together four monovalent live attenuated vaccine viruses has revealed the phenomenon of viral interference leading to the manifestation of immune responses biased towards a single serotype.

ResultsThis work stems from the emergence of i the DEN virus envelope E domain III EDIII as the most important region of the molecule from a vaccine perspective and ii the adenovirus Ad as a promising vaccine vector platform. We describe the construction of a recombinant, replication-defective Ad rAd vector encoding a chimeric antigen made of in-frame linked EDIIIs of DEN virus serotypes 2 and 4. Using this rAd vector, in conjunction with a plasmid vector encoding the same chimeric bivalent antigen, in a prime-boost strategy, we show that it is possible to elicit equipotent neutralizing and T cell responses specific to both DEN serotypes 2 and 4.

ConclusionOur data support the hypothesis that a DEN vaccine targeting more than one serotype may be based on a single DNA-based vector to circumvent viral interference. This work lays the foundation for developing a single Ad vector encoding EDIIIs of all four DEN serotypes to evoke a balanced immune response against each one of them. Thus, this work has implications for the development of safe and effective tetravalent dengue vaccines.

Electronic supplementary materialThe online version of this article doi:10.1186-1472-6750-7-10 contains supplementary material, which is available to authorized users.

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Author: Saima Khanam - Pilankatta Rajendra - Navin Khanna - Sathyamangalam Swaminathan

Source: https://link.springer.com/article/10.1186/1472-6750-7-10







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