Nanoparticles decorated with viral antigens are more immunogenic at low surface density

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• 作者：Matthew G. Brewer^a ; Anthony DiPiazza^a ; ^b ; Joshua Acklin^a ; Changyong Feng^c ; Andrea J. Sant^a ; ^b ; Stephen Dewhurst^a ; ^{stephen_dewhurst@urmc.rochester.edu}
• 关键词：HIV ; Envelope ; Influenza ; Hemagglutinin ; Nanoparticle ; Humoral immunity ; Antigen display ; Antigen density
• 刊名：Vaccine
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：35
• 期：5
• 页码：774-781
• 全文大小：1734 K
• 卷排序：35

文摘

There is an urgent need to develop protective vaccines for high priority viral pathogens. One approach known to enhance immune responses to viral proteins is to display them on a nanoparticle (NP) scaffold. However, little is known about the effect of protein density on the B cell response to antigens displayed on NPs. To address this question HIV-1 Envelope (Env) and influenza hemagglutinin (HA) were displayed on a polystyrene-based NP scaffold at various densities - corresponding to mean antigen distances that span the range encountered on naturally occurring virions. Our studies revealed that NPs displaying lower densities of Env or HA more efficiently stimulated antigen-specific B cells in vitro, as measured by calcium flux, than did NPs displaying higher antigen densities. Similarly, NPs displaying a low density of Env or HA also elicited higher titers of antigen-specific serum IgG in immunized BALB/c mice (including elevated titers of hemagglutination-inhibiting antibodies), as well as an increased frequency of antigen-specific antibody secreting cells in the lymph node, spleen and bone marrow. Importantly, our studies showed that the enhanced B cell response elicited by the lower density NPs is likely secondary to more efficient development of follicular helper CD4 T cells and germinal center B cells. These findings demonstrate that the density of antigen on a NP scaffold is a critical determinant of the humoral immune response elicited, and that high density display does not always result in an optimal response.