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.
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 approximately 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.
Programme in Infectious Diseases, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
C S
CS
Lim
John J E
JJ
Chua
Jamica
J
Wilkerson
Vincent T K
VT
Chow
D000417:Albinism; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions / Q000276:immunology*; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control; D003716:Dengue Virus / Q000145:classification* / Q000276:immunology*; D005416:Flavivirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C072281:E protein TH Sman, Dengue virus