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Differential dengue cross-reactive and neutralizing antibody responses in BALB/c and Swiss albino mice induced by immunization with flaviviral vaccines and by infection with homotypic dengue-2 virus strains.

MPG-Autoren
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Chua,  J. J.
Research Group of Protein Trafficking in Synaptic Development and Function, MPI for Biophysical Chemistry, Max Planck Society;

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Zitation

Lim, C. S., Chua, J. J., Wilkerson, J., & Chow, V. T. K. (2006). Differential dengue cross-reactive and neutralizing antibody responses in BALB/c and Swiss albino mice induced by immunization with flaviviral vaccines and by infection with homotypic dengue-2 virus strains. Viral Immunology, 19(1), 33-41. doi:10.1089/vim.2006.19.33.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0018-09BF-1
Zusammenfassung
We investigated whether cross-reactive and/or cross-protective antibodies against dengue virus could be generated in 6-week-old BALB/c mice by immunization with currently approved flaviviral vaccines, i.e., Japanese encephalitis (JE) BIKEN and yellow fever (YF) 17D. Cross-reactivity with dengue antigens was apparent in at least one-third each of JE-vaccinated mouse sera and of JE/YF-vaccinated mouse sera by dengue enzyme immunoassay, but was not detected in sera of mice immunized with YF vaccine alone. All the immunized BALB/c mice failed to generate neutralizing antibodies against the New Guinea C laboratory (NGC-lab) strain of dengue virus type 2. In addition, we determined the specificity of neutralizing antibodies elicited in 3-week-old Swiss albino mice against two homotypic dengue-2 strains, i.e., NGC-lab and Singapore 1999 (SING/99). Although sera from virus-inoculated mice displayed better neutralization against the corresponding strain, antibodies elicited by NGC-lab exhibited a significantly poorer neutralizing response against the SING/99 strain compared to antibodies elicited by SING/99 against NGC-lab. The differences may be related to sequence variations of ~3% between the envelope proteins of both strains. Amino acid disparities at positions 71 (Glu → Ala), 112 (Ser → Gly) and 124 (Ile → Asn), which are found in dengue-2 neutralization escape mutants, were also found in the SING/99 strain. The envelope sequence differences may explain diminished binding of NGC-lab–induced neutralizing antibodies to neutralizing epitopes within the envelope of the SING/99 strain, resulting in a lower titer of neutralizing antibodies against another strain of the same serotype.