Arch Virol (2001) 146: 2469–2479
Identiﬁcation of epitopes on the envelope (E) protein of dengue 2
and dengue 3 viruses using monoclonal antibodies
I. L. Seraﬁn and J. G. Aaskov
Centre for Molecular Biotechnology, School of Life Sciences,
Queensland University of Technology, Brisbane, Queensland, Australia
Accepted July 6, 2001
Summary. Of a panel of forty-six anti-dengue 3 monoclonal antibodies (MAbs)
only three neutralised infection of BHK cells by dengue 3 virus. Attempts to
select neutralisation escape mutants (n.e.m.) with two of these antibodies failed.
The n.e.m. population selected in the presence of the third neutralisingantibody,
1H9, had a nucleotide change at position 1157 of the E protein gene resulting
in a non-conservative amino acid change at E386 for a Lys to an Asn. A dengue
2 n.e.m. was selected with the ﬂavivirus crossreactive IgG monoclonal antibody
4G2, had deduced amino acid changes at E169 (Ser to Pro) and E275 (Gly to
Arg). This dengue 2 n.e.m. population produced smaller plaques in BHK cells
than the parental virus, decreased fusion activity (FFWI) and had lost the ability
to agglutinate gander erythrocyes at pH 6.0 to 6.7.
Dengue viruses (serotypes 1–4) are small, enveloped, positive-sense RNA
arboviruses, that are members of the genus Flavivirus in the family Flaviviridae
. They cause disease in humans varyingfrom mild (dengue fever, DF) to
potentially fatal (dengue haemorrhagic fever, DHF; dengue shock syndrome,
DSS). It has been estimated that two-ﬁfths of the world’s population is at risk
of infection; that an estimated 50 million infections occur annually with an esti-
mated 500,000 cases of DHF annually .
A safe, effective and inexpensive vaccine against dengue infection is required.
The ideal vaccine would protect against all four dengue serotypes and provide
long-lasting immunity against dengue infection [3, 13, 32]. The vaccine should
also be able to produce greater than 95% seroconversion, and be able to be admin-
istered to children between the ages of 6 months and one year . Importantly,
the vaccine should not sensitise vaccinees to DHF/DSS .