The function and affinity maturation of HIV-1 gp120-specific monoclonal antibodies derived from colostral B cells
Despite the risk of transmitting HIV-1, mothers in resource-poor areas are encouraged to breastfeed their infants because of beneficial immunologic and nutritional factors in milk. Interestingly, in the absence of antiretroviral prophylaxis, the overwhelming majority of HIV-1-exposed, breastfeeding infants are naturally protected from infection. To understand the role of HIV-1 envelope (Env)-specific antibodies in breast milk in natural protection against infant virus transmission, we produced 19 HIV-1 Env-specific monoclonal antibodies (mAbs) isolated from colostrum B cells of HIV-1-infected mothers and investigated their specificity, evolution, and anti-HIV-1 functions. Despite the previously reported genetic compartmentalization and gp120-specific bias of colostrum HIV Env-specific B cells, the colostrum Env-specific mAbs described here demonstrated a broad range of gp120 epitope specificities and functions, including inhibition of epithelial cell binding and dendritic cell-mediated virus transfer, neutralization, and antibody-dependent cellular cytotoxicity. We also identified divergent patterns of colostrum Env-specific B-cell lineage evolution with respect to cross-reactivity to gastrointestinal commensal bacteria, indicating that commensal bacterial antigens play a role in shaping the local breast milk immunoglobulin G (IgG) repertoire. Maternal vaccine strategies to specifically target this breast milk B-cell population may be necessary to achieve safe breastfeeding for all HIV-1-exposed infants. read or download the entire article Colostrum & HIV here
Intensification of Antiretroviral Therapy With Raltegravir or Addition of Hyperimmune Bovine Colostrum in HIV-Infected Patients With Suboptimal CD4+ T-Cell Response
Combination antiretroviral therapy (cART) in human immunodeficiency virus (HIV)–infected individuals is associated with control of viral replication and immune recovery. In the majority of patients, this response is associated with increases in CD4+ T cells in peripheral blood . However, the extent of CD4+ T-cell recovery following cART is highly variable [2, 3]. Despite achieving reliable and sustained suppression of viral replication, up to 30% of patients exhibit the suboptimal increase in CD4+ T-cell count [2, 4, 5]. Disconcertingly, a greater risk of non-AIDS-related complications is consistently observed in patients with lower CD4+T-cell counts on suppressive therapy [6, 7].
The factors that have been consistently associated with limited CD4+ T-cell recovery in patients on cART include advanced age [2, 8, 9], viral coinfection [10, 11], and a lower nadir CD4+ T-cell count [9, 12]. Persistent immune activation is thought to play an important role in poor immunological response to cART [13–15]. Two potential mechanisms have been proposed as a continuous trigger of immune activation in untreated chronic HIV infection. First, HIV-associated damage to intestinal mucosal integrity may result in increased microbial translocation into the circulation from the gastrointestinal lumen, though this observation is not consistently demonstrated [16–19]. Second, persistent low-level HIV replication, even in the setting of suppressive cART, may result in persistent immune activation [20, 21]. The observation of higher levels of proviral DNA in memory and naive CD4+ T cells of patients with poor CD4+ T-cell recovery on suppressive cART supports the hypothesis that HIV antigen-driven CD4+ T-cell activation may play a key role in the continuous loss of CD4+ T-cell loss in these individuals . read the entire article Here