Immunotherapy for Infectious Diseases

INTRODUCTION
From: Immunotherapy for Infectious Diseases
Edited by: J. M. Jacobson © Humana Press Inc., Totowa, NJ
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Passive Immunotherapy for HIV Infection
Jeffrey M. Jacobson
The importance of humoral immunity in the prevention and control of natural HIV
infection is unclear. Neutralizing antibody production can be detected soon after acute
infection (1). In addition, antibodies capable of neutralization and antibody-dependent
cellular cytotoxicity (ADCC) remain present to a greater degree in those patients whose
infections remain stable (2,3). Patients with progressing infection tend to lose these
antibody activities. Moreover, levels of HIV-directed maternal antibodies are associated
with reduced transmission of HIV to the infant (4–6). However, the nature of the relationship
between strong humoral responses and control of infection has not been established.
Strong HIV-specific cellular immune responses are also seen after acute infection
(7) and in long-term nonprogressors (8), and there is more compelling evidence of a
greater role of these responses in controlling HIV replication (9).
Passive immunization with pathogen-specific antibodies is protective against infection
with a number of other organisms. These include rabies virus (10), respiratory syncytial
virus (11), cytomegalovirus (12), hepatitis A and B viruses (13,14),
varicella-zoster virus (15), poliovirus (16), measles virus (17), rubella virus (18), and
mumps virus (19). In addition, this form of treatment has proved effective in the management
of established infections with respiratory syncytial virus (11), cytomegalovirus
(20), parvovirus B19 (21), hepatitis B virus (22), and Junin arenavirus (Argentine hemorrhagic
fever) (23), as well as pneumococcal pneumonia (24), meningococcal meningitis
(23), and Hemophilus influenzae meningitis (23). The knowledge learned from
these interventions contributed to the successful development of effective vaccines
against many of these infectious agents (23). Thus, the potential role of passive immunization
in preventive and therapeutic strategies against HIV infection deserves further
attention.
IN VITRO DATA
HIV Envelope Structure
As a monomer, the gp120 envelope protein of HIV has five variable loops (V1–V5)
and five constant regions (C1–C5) that are potential targets for antibody binding (23).
However, in its natural state on the surface of the virus as a trimer, conformational