[CITATION][C] Human monoclonal antibodies for passive immunotherapy of HIV-1

H Katinger - Advanced Technologies in Research, Diagnosis and …, 1994 - karger.com
H Katinger
Advanced Technologies in Research, Diagnosis and Treatment of AIDS and in …, 1994karger.com
The role of the humoral immune response in the defense of HIV-1-related pathogenesis
demands still further enlightenment. Specific immune responses have been observed
against a variety of continuous and discontinuous HIV-1 epitopes. Usually, sera from
infected individuals show high to medium titers of neutralizing antibodies when tested
against various HIV-1 laboratory strains [I]. However, most sera show moderate or even no
neutralizing activity against their homologous virus isolates [2, 3]. Even the fact that the …
The role of the humoral immune response in the defense of HIV-1-related pathogenesis demands still further enlightenment. Specific immune responses have been observed against a variety of continuous and discontinuous HIV-1 epitopes. Usually, sera from infected individuals show high to medium titers of neutralizing antibodies when tested against various HIV-1 laboratory strains [I]. However, most sera show moderate or even no neutralizing activity against their homologous virus isolates [2, 3]. Even the fact that the neutralizing spectrum of antibodies is triggered from a type-specific reaction to a more broad and group-specific type of neutralization is not sufficient to prevent the generation of escape mutants over the years. These escape mutants are probably one reason for disease progression of AIDS.
The topography of the HIV-I surface has been investigated by many groups and is still subject of ongoing studies. Neutralizing regions have been mapped on the envelope protein gp120 and the transmembrane protein gp41. Early after seroconversion, a neutralizing humoral immune response is observed in a rather type-specific manner against the V3 loop of gpl20 [4]. Only few antibodies directed against the PND are known to possess broad neutralizing capacity [5]. It has also been shown that in seropositive individuals antibodies are generated against discontinuous epitopes which interfere with CD4 binding and which show broad neutralization [6, 7]. The majority of antibodies in infected individuals show specific binding activity to various HIV-I antigens but are not neutralizing. Cellular and humoral antigenic epitopes in HIV (and SIV) have been recently reviewed by Nixon et al.[8]. Antibodies directed against carbohydrate moieties on gp160 may also play an important part in the humoral neutralization defense of HIV [9, 10].
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