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against primary isolates.
100
The use of this model for the evaluation of
antibody efficacy is limited due to concerns regarding the route of
viral challenge in the mouse model. However, the presence of human
cells in the context of the peritoneal and lymph node architecture,
complement and phagocytic cells, and the ability to sustain viral infec-
tion make it an interesting initial model to test the protective efficacy
of passively administered antibodies.
To better understand the qualitative and quantitative characteris-
tics of antibody-mediated protection against HIV-1, Parren and col-
leagues and Mascola and colleagues used a rhesus macaque challenge
model, where animals were passively transfused with neutralizing anti-
bodies and then challenged with the chimeric simian/human immun-
odeficiency virus (SHIV).
101-103
These viruses contain the Env from
HIV-1 and structural proteins from SIV, and are pathogenic in
macaques, thereby allowing evaluation of the protective efficacy of
antibodies directed against Env. Parren and colleagues passively trans-
ferred different concentrations of mAb b12 and then challenged the
animals. It was observed that the protection afforded by b12 to rhe-
sus macaques against SHIVSF162P4 is concentration dependent
(Fig. 6A). At the concentration of 25 mg/kg of the antibody, all the
animals were solidly protected. However, at a 5 mg/ kg level, 50% of
the animals were protected. Not surprisingly, at the lowest concen-
tration of 1 mg/kg, none of the animals were protected against the
challenge. Mascola and colleagues have demonstrated that a combi-
nation of neutralizing antibodies (HIVIG, 2F5, 2G12) was protective
against i.v. challenge,
104
where two out of three animals were com-
pletely protected while the third animal had a two-log reduction in
viral load set point and CD4
+
T-cells were also preserved. However,
in follow-up experiments it was shown that passive transfer of single
antibodies (2F5 or 2G12 or HIVIG) did not protect the animals
against the challenge infection because all the animals were infected,
104
suggesting that breadth of immune response may be critical for the
protective efficacy. This was contrary to what was observed for b12;
however, the challenge virus was different for these studies, and dif-
ferent mAbs were used for passive transfers. Since the primary mode
