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Vaccine. 2017 Feb 1;35(5):774-781. doi: 10.1016/j.vaccine.2016.12.049. Epub 2017 Jan 3.

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

Author information

1
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, United States.
2
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, United States; David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, United States.
3
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, United States.
4
Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, United States. Electronic address: stephen_dewhurst@urmc.rochester.edu.

Abstract

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.

KEYWORDS:

Antigen density; Antigen display; Envelope; HIV; Hemagglutinin; Humoral immunity; Influenza; Nanoparticle

PMID:
28057386
PMCID:
PMC5876043
DOI:
10.1016/j.vaccine.2016.12.049
[Indexed for MEDLINE]
Free PMC Article

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