Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation.

To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) contribute to protection against several pathogens. In this study, we demonstrated that conjugation of HIV Envelop (Env) antigen gp120 to a self-assembling nanofiber material named Q11 induced antibodies with higher breadth and functionality when compared to soluble gp120. Immunization with Q11-conjugated gp120 vaccine (gp120-Q11) demonstrated higher tier 1 neutralization, ADCP and ADCC as compared to soluble gp120. Moreover, Q11 conjugation altered the Fc N-glycosylation profile of antigen-specific antibodies, leading to a phenotype associated with increased ADCC in animals immunized with gp120-Q11. Thus, this nanomaterial vaccine strategy can enhance non-neutralizing antibody functions possibly through modulation of IgG Fc N-glycosylation.针对HIV等全球重点病原体开发疫苗时，诱导同时具备中和活性与非中和活性的Fc介导效应抗体功能至关重要。临床研究证据表明，包括抗体依赖性细胞毒性（antibody-dependent cellular cytotoxicity, ADCC）与抗体依赖性细胞吞噬作用（antibody-dependent cellular phagocytosis, ADCP）在内的非中和抗体功能，可对多种病原体感染提供保护作用。本研究证实，将HIV包膜（Envelope, Env）抗原gp120与名为Q11的自组装纳米纤维材料偶联后，所诱导产生的抗体相较于可溶性gp120免疫组，具有更广的广谱性与更强的功能活性。与可溶性gp120组相比，Q11偶联gp120疫苗（gp120-Q11）免疫后可诱导产生更高水平的1型中和活性、ADCP与ADCC效应。此外，Q11偶联修饰改变了抗原特异性抗体的Fc N-糖基化谱，使得gp120-Q11免疫动物体内的抗体呈现出与ADCC活性增强相关的表型特征。综上，该纳米材料疫苗策略可通过调控IgG的Fc N-糖基化修饰，增强非中和抗体的功能活性。