Institute of Biomedical Sciences

Title

Characterizing antibody responses in ART-treated patients

Document Type

Poster

Abstract Category

HIV/AIDS

Keywords

HIV, ART, Antibodies

Publication Date

Spring 5-1-2019

Abstract

Although antiretroviral therapy (ART) suppresses HIV replication, ART-treated individuals must maintain therapy to avoid rebound from a viral reservoir. Strategies to limit or clear this reservoir are urgently needed. Recent research has indicated that patients living with HIV longer prior to treatment may harbor more diverse reservoirs, but also that these patients often exhibit higher anti-HIV antibody titers. The roles virus diversity and length of treatment play in the humoral immune response must be further studied to inform multi-pronged approaches to clearing infection. Here, we aim to elucidate roles for autologous antibodies in these treatments by characterizing the functional anti-HIV antibody response in individuals with different lengths of ART. Plasma was collected from 8 HIV-infected males on ART. Bulk IgG was isolated from plasma in order to remove ART from downstream assays. IgG was quantified by ELISA and normalized concentrations were tested for binding affinity to gp41 and gp120 proteins by indirect ELISA. IgG was then tested for breadth of neutralization in TZM-bl assays against a global HIV pseudovirus panel. IgG binding against gp41 was present in all plasma and was highly correlated with titer against gp120 (r = 0.86 p = 0.01). Surprisingly 3 of the 8 individuals had low or undetectable titers to gp120. On average, plasma exhibited heterologous neutralization against 8 of 12 viruses on a global HIV panel. This neutralization was typically not potent. The strongest neutralizers were two participants who had been infected for 75 and 57 months prior to receiving ART, the longest periods of replication in the study. Potency of neutralization against the global HIV panel correlated with time of infection before ART (r = 0.83; p = 0.02), but not with duration of ART. Our findings agree with published studies of untreated individuals that length of infection correlates with neutralization of a global panel. Interestingly, we found that durations of treatment were not associated with differences in neutralization. These data suggest that individuals who are treated early with ART may have less neutralization breadth than those treated late, but not lower antibody titers

Open Access

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Presented at Research Days 2019.

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Characterizing antibody responses in ART-treated patients

Although antiretroviral therapy (ART) suppresses HIV replication, ART-treated individuals must maintain therapy to avoid rebound from a viral reservoir. Strategies to limit or clear this reservoir are urgently needed. Recent research has indicated that patients living with HIV longer prior to treatment may harbor more diverse reservoirs, but also that these patients often exhibit higher anti-HIV antibody titers. The roles virus diversity and length of treatment play in the humoral immune response must be further studied to inform multi-pronged approaches to clearing infection. Here, we aim to elucidate roles for autologous antibodies in these treatments by characterizing the functional anti-HIV antibody response in individuals with different lengths of ART. Plasma was collected from 8 HIV-infected males on ART. Bulk IgG was isolated from plasma in order to remove ART from downstream assays. IgG was quantified by ELISA and normalized concentrations were tested for binding affinity to gp41 and gp120 proteins by indirect ELISA. IgG was then tested for breadth of neutralization in TZM-bl assays against a global HIV pseudovirus panel. IgG binding against gp41 was present in all plasma and was highly correlated with titer against gp120 (r = 0.86 p = 0.01). Surprisingly 3 of the 8 individuals had low or undetectable titers to gp120. On average, plasma exhibited heterologous neutralization against 8 of 12 viruses on a global HIV panel. This neutralization was typically not potent. The strongest neutralizers were two participants who had been infected for 75 and 57 months prior to receiving ART, the longest periods of replication in the study. Potency of neutralization against the global HIV panel correlated with time of infection before ART (r = 0.83; p = 0.02), but not with duration of ART. Our findings agree with published studies of untreated individuals that length of infection correlates with neutralization of a global panel. Interestingly, we found that durations of treatment were not associated with differences in neutralization. These data suggest that individuals who are treated early with ART may have less neutralization breadth than those treated late, but not lower antibody titers