Immunotherapy for Infectious Diseases

From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
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Active Immunization as Therapy for HIV Infection
INTRODUCTION
Spyros A. Kalams
Emerging data over the past several years have confirmed the role of the HIV-specific
immune response in determining viral setpoint and delaying HIV disease progression.
Despite advances in the control of HIV-1 viremia with highly active antiretroviral therapy
(HAART), these therapies carry the risk of toxicities with long-term use. This has
led to accelerated efforts designed to augment HIV-1-specific immune responses in
infected subjects with the hope that the use of antiretroviral medications can be reduced
or eliminated. This chapter reviews the current state of knowledge regarding the immune
responses directed against HIV and summarizes efforts that are in progress or that will
be under way to augment these responses in infected individuals.
IMMUNE RESPONSES
IN CONTROLLED CHRONIC VIRAL INFECTIONS
Although there are examples of acute infections with viruses that are subsequently
cleared by the immune system (e.g., influenza), for several viral infections recovery
from illness is the result of immune-based containment of viremia. Patients with acute
Epstein-Barr virus (EBV) infection contain the initial infection with a vigorous immune
response, yet despite almost uniform resolution of symptoms, the virus remains present
for the life of the infected individual. In the presence of an intact immune response,
viremia is contained, and disease does not recur. Evidence for the continued need
for immune surveillance is provided by the well-documented occurrence of EBVassociated
malignancies in patients on immunosuppressive agents, as well as the
regression of tumors when immunosuppression is decreased (1,2).
The lymphocytic choriomeningitis virus (LCMV) infection model in mice has been
a useful tool for dissecting the roles of the humoral and cellular immune system in viral
containment. After acute infection there are large expansions of CD8� T-cells (CTLs)
and up to 70% of total CD8 T-cells are LCMV-specific 8 days after infection (3,4).
Another important component of immune control is the virus-specific T-helper cell
response. If CD4 T-cells are either absent by genetic knockout of CD4, or depleted by
anti-CD4 antibodies CTL are still generated, but they decline during the chronic phase
of infection. In this instance viremia is not controlled. These studies suggest that in this