Chimpanzee Fab fragments and a derived humanized immunoglobulin G1 antibody that efficiently cross-neutralize dengue type 1 and type 2 viruses.
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TL;DR: The phage library constructed from the chimpanzees was used to recover Fab antibodies against the other three DENV serotypes and this humanized antibody represents an attractive candidate for further development of immunoprophylaxis against DENV and perhaps other flavivirus-associated diseases.
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Abstract: Passive immunization with monoclonal antibodies from humans or nonhuman primates represents an attractive alternative to vaccines for prevention of illness caused by dengue viruses (DENV) and other flaviviruses, including the West Nile virus. In a previous study, repertoire cloning to recover Fab fragments from bone marrow mRNA of chimpanzees infected with all four DENV serotypes (dengue virus serotype 1 [DENV-1] to DENV-4) was described. In that study, a humanized immunoglobulin G1 (IgG1) antibody that efficiently neutralized DENV-4 was recovered and characterized. In this study, the phage library constructed from the chimpanzees was used to recover Fab antibodies against the other three DENV serotypes. Serotype-specific neutralizing Fabs were not identified. Instead, we recovered DENV-neutralizing Fabs that specifically precipitated the envelope protein and were cross-reactive with all four DENV serotypes. Three of the Fabs competed with each other for binding to DENV-1 and DENV-2, although each of these Fabs contained a distinct complementarity determining region 3 (CDR3)-H sequence. Fabs that shared an identical or nearly identical CDR3-H sequences cross-neutralized DENV-1 and DENV-2 at a similar high 50% plaque reduction neutralization test (PRNT50) titer, ranging from 0.26 to 1.33 μg/ml, and neutralized DENV-3 and DENV-4 but at a titer 10- to 20-fold lower. One of these Fabs, 1A5, also neutralized the West Nile virus most efficiently among other flaviviruses tested. Fab 1A5 was converted to a full-length antibody in combination with human sequences for production in mammalian CHO cells. Humanized IgG1 1A5 proved to be as efficient as Fab 1A5 for cross-neutralization of DENV-1 and DENV-2 at a titer of 0.48 and 0.95 μg/ml, respectively. IgG1 1A5 also neutralized DENV-3, DENV-4, and the West Nile virus at a PRNT50 titer of approximately 3.2 to 4.2 μg/ml. This humanized antibody represents an attractive candidate for further development of immunoprophylaxis against DENV and perhaps other flavivirus-associated diseases.
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References
Dengue and Dengue Hemorrhagic Fever
TL;DR: A review of the changing epidemiology of dengue and hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both Dengue fever and DVF, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control can be found in this paper.
Designing Human Antibodies by Phage Display
André Frenzel,Jonas Kügler,Saskia Helmsing,Doris Meier,Thomas Schirrmann,Michael Hust,Stefan Dübel +6 more
TL;DR: Some opportunities and achievements are summarized, e.g., the generation of antibodies which could not be generated otherwise, and the design of antibody properties by different panning strategies, including the adjustment of kinetic parameters.
Dengue and dengue hemorrhagic fever.
Edward B. Hayes,Duane J. Gubler +1 more
TL;DR: A major challenge for public health officials in all tropical areas of the world is to develop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever.
1.7K
Pathogenesis of dengue: challenges to molecular biology
TL;DR: This work has identified a severe syndrome, dengue hemorrhagic fever/dengue shock syndrome, in Southeast Asian children, which recently has also been identified in children infected with the virus in Puerto Rico.
1.7K
Assembly of combinatorial antibody libraries on phage surfaces: the gene III site.
TL;DR: A phagemid system was developed for the monovalent display of combinatorial antibody Fab libraries on the surface of filamentous phage M13, and may replace current antibody cloning techniques.
1.6K