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limited by antibody affinity. The well-known logistic growth equation is used to
model affinity maturation in response to an epitope in the viral population. The affin-
ity of an antibody to an epitope is
N
t
=
K
/ 1+
K
/
N
0
−1
( )
e
−
r
[ ]
(1)
where
t
is the number of viral generations of stimulation (maturity),
K
is the maxi-
mum affinity (ranging from 0 to 1),
N
0
is the affinity at
t
= 0, and
r
is the intrinsic
rate of increase of affinity (rate of increase when
N
t
is small). Once the production of
an antibody has been stimulated (see below),
t
is incremented for each viral genera-
tion in which the targeted epitope is present. The probability of neutralization of a
virion that carries the epitope targeted by the antibody is
N
t
, and the probability of
neutralization escape is 1 -
N
t
. The neutralization component of fitness for a virion
then is the product of the neutralization escape probabilities associated with each
antibody that targets epitopes contained in the virion's V3 sequences.
The V3 linear epitopes of known monoclonal neutralizing antibodies produced
during HIV-1 subtype B infection of humans are shown in Table 1. Before any of
these antibodies can affect virion fitness, their initial production must be stimulated.
Table 1.
Monoclonal neutralizing antibodies that target V3, generated during HIV-1 subtype
B infection of humans, and their epitopes.
from the HIV Molecular Immunology Database.
A period indicates any amino acid. Data are
Monoclonal antibody
V3 epitope
412-D
RKRIHIGPGRAFYTT
DO142-10
KRIHIGPGRAFYTT
391/95-D
KRIHIGPGRAFY
41148D
KRIHIGP
311-11-D
KRIHIGP
257-D
KRIHI
908-D
KSITKG
782-D
KSITKG
838-D
KSITK
MN215
RIHIGPGRAFYTTKN
19b
I....G..FY.T
419-D
IHIGPGR
504-D
IHIGPGR
453-D
IHIGPGR
4117C
I.IGPGR
418-D
HIGPGRA
386-D
HIGPGR
268-D
HIGPGR
537-D
IGPGR
447-52D
GP.R
N70-1.9b
PGRAFY
694/98-D
GRAF
