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Review
. 2011 Sep 23;29(42):7242-50.
doi: 10.1016/j.vaccine.2011.07.023. Epub 2011 Jul 21.

Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine

Affiliations
Review

Development and clinical evaluation of multiple investigational monovalent DENV vaccines to identify components for inclusion in a live attenuated tetravalent DENV vaccine

Anna P Durbin et al. Vaccine. .

Abstract

The Laboratory of Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health has been engaged in an effort to develop a safe, efficacious, and affordable live attenuated tetravalent dengue vaccine (LATV) for more than ten years. Numerous recombinant monovalent DENV vaccine candidates have been evaluated in the SCID-HuH-7 mouse and in rhesus macaques to identify those candidates with a suitable attenuation phenotype. In addition, the ability of these candidates to infect and disseminate in Aedes mosquitoes had also been determined. Those candidates that were suitably attenuated in SCID-HuH-7 mice, rhesus macaques, and mosquitoes were selected for further evaluation in humans. This review will describe the generation of multiple candidate vaccines directed against each DENV serotype, the preclinical and clinical evaluation of these candidates, and the process of selecting suitable candidates for inclusion in a LATV dengue vaccine.

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Figures

Figure 1
Figure 1
Recombinant attenuated DENV vaccine candidates were constructed by deletion of nucleotides from the 3′ UTR (Δ30 and Δ30/31) or by chimerization of genomic regions from different serotypes. Representations for each vaccine candidate are shown with DENV-1 sequence elements shown in white, DENV-2 elements shown in hatched lines, DENV-3 elements shown as speckled, and DENV-4 elements shown in gray. Genome regions are not drawn to scale.

References

    1. Halstead SB, Vaughn DW. In: Dengue vaccines. Plotkin S, Orenstein WA, Offit PA, editors. Elsevier; Vaccines: 2008.
    1. Burke DS, Nisalak A, Johnson DE, Scott RM. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg. 1988;38(1):172–80. - PubMed
    1. Gibbons RV, Kalanarooj S, Jarman RG, Nisalak A, Vaughn DW, Endy TP, et al. Analysis of repeat hospital admissions for dengue to estimate the frequency of third or fourth dengue infections resulting in admissions and dengue hemorrhagic fever, and serotype sequences. Am J Trop Med Hyg. 2007 Nov;77(5):910–3. - PubMed
    1. Vaughn DW, Green S, Kalayanarooj S, Innis BL, Nimmannitya S, Suntayakorn S, et al. Dengue Viremia Titer, Antibody Response Pattern, and Virus Serotype Correlate with Disease Severity. J Infect Dis. 2000;181(1):2–9. - PubMed
    1. Morrison D, Legg TJ, Billings CW, Forrat R, Yoksan S, Lang J. A novel tetravalent dengue vaccine is well tolerated and immunogenic against all 4 serotypes in flavivirus-naive adults. J Infect Dis. 2010 Feb 1;201(3):370–7. - PubMed

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