Abstract
Recent progress toward an HIV vaccine highlights both the potential of vaccines to end the AIDS pandemic and the need to boost efficacy by incorporating additional vaccine strategies. Although many aspects of the immune response can contribute to vaccine efficacy, the key factors have not been defined fully yet. A particular area that may yield new insights is anti-glycan immune responses, such as those against the glycan shield that HIV uses to evade the immune system. In this study, we used glycan microarray technology to evaluate anti-glycan antibody responses induced by SIV vaccination and infection in a non-human primate model of HIV infection. This comprehensive profiling of circulating anti-glycan antibodies found changes in anti-glycan antibody levels after both vaccination with the Ad5hr-SIV vaccine and SIV infection. Notably, SIV infection produced generalized declines in anti-glycan IgM antibodies in a number of animals. Additionally, some infected animals generated antibodies to the Tn antigen, which is a cryptic tumor-associated antigen exposed by premature termination of O-linked glycans; however, the Ad5hr-SIV vaccine did not induce anti-Tn IgG antibodies. Overall, this study demonstrates the potential contributions that glycan microarrays can make for HIV vaccine development.
Highlights
A vaccine for HIV offers the best prospects for ending the AIDS pandemic, and intense efforts have been directed toward HIV vaccine development
High-mannose as well as complex-type N-glycans are recognized by the recently identified V3 loop binding antibody, PGT121 [8]. These findings suggest that serum anti-glycan antibodies may be critical for preventing and controlling HIV infection, and carbohydratetargeted HIV vaccines are under development [9,10]
Simian immunodeficiency virus (SIV) infected macaques are an established model for HIV infection of humans, we first compared the anti-glycan antibody profiles of humans and macaques to confirm that macaques are a relevant model for this aspect of humoral immunity
Summary
A vaccine for HIV offers the best prospects for ending the AIDS pandemic, and intense efforts have been directed toward HIV vaccine development. This work has culminated in a recent study that demonstrated the first evidence of efficacy in a phase III clinical trial for an HIV vaccine [1]. While this groundbreaking study has shown that an HIV vaccine can provide protection from infection, the overall efficacy was modest and significant improvements still are urgently needed. High-mannose as well as complex-type N-glycans are recognized by the recently identified V3 loop binding antibody, PGT121 [8]. These findings suggest that serum anti-glycan antibodies may be critical for preventing and controlling HIV infection, and carbohydratetargeted HIV vaccines are under development [9,10]. Due to the technical challenges associated with analysis of complex mixtures of serum anti-glycan antibodies, there has been no comprehensive characterization of how HIV vaccines or infection alter levels of antibodies to diverse glycans in humans
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