Neutralizing and enhancing antibodies measured in complement-restored serum samples from HIV-1 -infected individuals correlate with immunosuppression and disease

Comparison of Human Immunodeficiency Virus (HIV)-Specific Infection-Enhancing and -Inhibiting Antibodies in AIDS Patients

“…All four complement receptors have been demonstrated to bind to HIV-1 and mediate infection in the presence of complement in different human cell types (30,47,49,52). Several researchers have demonstrated that the ability of sera to enhance HIV infection in the presence of complement correlated with the progression toward AIDS (15,18,43,48). This may be the reason why CR2-positive CD4 ϩ T cells are preferentially depleted in HIV-infected patients (20).…”

“…All known complement receptors may be used for this process (14,30,49,52). This type of enhancement has been documented with fresh serum or plasma from patients infected with HIV and by adding complement to sera from these patients if the sera had been heat inactivated (15,37). The complement-independent IEAs enhance HIV infections by mediating binding of virions to Fc receptors (FcRs) on target cells and therefore are FcR-dependent IEAs (FcR-IEAs).…”

Predominance of Detrimental Humoral Immune Responses to HIV‐1 in AIDS Patients with CD4 Lymphocyte Counts Less Than 400/mm3

“…Not all humoral responses to lentivirus infection are beneficial to the host. The ability of antibody to enhance virus infection in cells expressing complement and/or antibody Fc receptors has been well-documented [17,[22][23][24][25][26][27][28][29]. The titres of C 0 -ADE antibodies against HIV LAI are illustrated in Table 1.…”

“…Serum from HIV-1 infected individuals contains antibodies that can mediate ACC if animal complement is used [18,19] but not if human complement is used [20]. Furthermore, if complement is added, one can measure C 0 -ADE of HIV infection where complement activated by antibody bound to HIV envelope glycoproteins interacts with complement receptors on the cell surface [17,[21][22][23][24][25][26][27][28][29] to increase virus infection. To date, a correlation between C 0 -ADE and disease progression has been noted by one group [24] but it remains controversial [25]; although, in rhesus macaques it has been shown that enhancing antibody titres increase with disease progression [26,27,30], the author concluded that enhancing antibody titre was not a significant cofactor in vaccine failure [27].…”

“…Furthermore, if complement is added, one can measure C 0 -ADE of HIV infection where complement activated by antibody bound to HIV envelope glycoproteins interacts with complement receptors on the cell surface [17,[21][22][23][24][25][26][27][28][29] to increase virus infection. To date, a correlation between C 0 -ADE and disease progression has been noted by one group [24] but it remains controversial [25]; although, in rhesus macaques it has been shown that enhancing antibody titres increase with disease progression [26,27,30], the author concluded that enhancing antibody titre was not a significant cofactor in vaccine failure [27]. Furthermore, in two recent studies it was reported that higher levels of antibody to the enhancing domain correlated with poor prognosis in immunized rhesus macaques subsequently challenged with uncloned macaque isolate 251 of the simian immunodeficiency virus (SIV mac251 ) [28,29].…”