Immunotherapy for Infectious Diseases

206 Jacobson
from the SIV/17E-Cl-infected macaques protected two of four uninfected macaques
from challenge with a heterologous monocyte-tropic primary virus isolate,
SIV/DeltaB670 (102).
Postexposure Protection Studies
in Monkeys Using Polyclonal Antibody Preparations
Passive immunization has been promoted as a possible strategy for prevention of
infection in the immediate postexposure period. Human HIVIG was found to be ineffective
at preventing infection with HIVIIIB when given 1 and 4 hours after viral challenge.
However, the 1-hour post exposure administration seemed to modify the course
of the infection by lowering plasma HIV RNA levels and the frequency of virus isolation
(A.M. Prince, personel communication).
Haigwood et al. (103) gave immune globulin produced from the plasma of an SIVinfected
“long-term nonprogressor” macaque to other macaques 1 and 14 days after acute
infection with SIVsmE660. Control animals received noninfected immune globulin before
challenge with virus. Four of six macaques treated with SIVIG had marked reductions in
plasma viral RNA and remained asymptomatic for at least 15 months, whereas 9 of 10 control
animals had high and increasing viral loads and progressed to AIDS. The animals with
stable disease developed de novo virus-specific antibodies and cytotoxic T-lymphocyte
(CTL) activity, responses characteristic of long-term nonprogressors (103).
When the SIV hyperimmune serum prepared by Van Rompay et al. (100),which was
effective in the preexposure setting, was administered to three newborn macaques 3
weeks after oral SIVmac251 challenge, plasma SIV RNA levels were not affected, and
all three animals died within 3 months.
Of course, these studies differ in the nature of the antibody preparation used, the
challenge virus, the animal species, and the age of the challenged animals. However,
when the studies are taken together, there is clearly a suggestion that the passive administration
of antibodies, prepared and dosed properly, could affect the outcome of infection
when administered before or immediately after exposure to virus.
Protection Studies in Monkeys Using Monoclonal Antibodies
Monoclonal antibodies have also been evaluated in primate protection models.
Emini et al. (35) demonstrated protection of chimpanzees against HIV-1IIIB infection
with an anti-HIV-1IIIB V3 loop monoclonal antibody administered either before or
shortly after (approx. 10 minutes) virus challenge. Kent et al. (98) reported the failure
of a pool of four neutralizing monoclonal antibodies directed against SIVmac gp120 to
protect any of four macaques against challenge with SIVmac251. Conley et al. (104) studied the ability of the anti-HIV gp41 monoclonal antibody
2F5 to protect chimpanzees against an intravenous challenge with a primary monocytetropic
HIV-1 isolate. This monoclonal antibody has in vitro neutralizing activity against
approx. 75% of primary isolates, including the challenge virus, designated 5016. The
two control animals became plasma HIV-1 RNA positive within 1 week of virus challenge.
The two antibody-treated animals were also infected, but infection was delayed
in both animals (first detection of HIV RNA in plasma at weeks 8 and 14), and peak
plasma viral RNA was significantly lower in one animal than in the control animals.
Thus, although not demonstrating protection, treatment with this monoclonal antibody
appeared to alter the course of the HIV infection (104).