Shape and size-dependent immune response to antigen-carrying nanoparticles

Kumar, Sunny; Anselmo, Aaron C.; Banerjee, Amrita; Zakrewsky, Michael; Mitragotri, Samir

doi:10.1016/j.jconrel.2015.09.069

Cited by 263 publications

(183 citation statements)

References 58 publications

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“…However, it is poorly understood how protein density influences the magnitude and quality of immune responses to NP displayed antigens [9]. Previous studies have used complex systems, including haptens, micron sized conjugates, or combinations of antigen/adjuvants to understand antigen density and its effects on host immunity [6, 29, 30].…”

Section: Discussionmentioning

confidence: 99%

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

Brewer

DiPiazza

Acklin

et al. 2017

Vaccine

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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

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Section: Discussionmentioning

confidence: 99%

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

Brewer

DiPiazza

Acklin

et al. 2017

Vaccine

View full text Add to dashboard Cite

show abstract

“…In other studies using antigen-coated polystyrene rods and spheres of different sizes, smaller sizes promoted T helper (Th)1 biased response in the case of the spherical geometries. Conversely, for rod-shaped particles, increasing length, but not width, correlated with a Th2 biased response [22]; possibly because longer particles presented a greater antigen density and surface area for attachment or internalization. Together, these results highlight the importance of particle size in trafficking, uptake by APCs, activation, and subsequent biasing of adaptive response (Figure 2A, center).…”

Section: Biomaterials Exhibit Physicochemical Properties That Can Trimentioning

confidence: 99%

Improving Vaccine and Immunotherapy Design Using Biomaterials

Bookstaver

Tsai

Bromberg

et al. 2018

Trends in Immunology

157

113

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“…Rod-like NVs have shown reduced non-specific and enhanced specific uptake (through antigen display) in breast cancer cell lines when compared to spherical particles, with greater inhibition of cell growth [93]. It has also been shown that in certain applications the interplay between size and shape is more complex with immune responses of antigen-modified particles varying between spherical and rod-like particles [94], which highlights that morphology should be varied in response to biochemical findings. Further examples of successfully implemented NVs that utilise the favourable properties of shape towards increasing their therapeutic effect are now in development and hopefully, as a result of the present review, will be seen as the figurative descendant of the past few decades of nanomedical research.…”

Section: Impact Of Nanovector Morphology On Performance In Vitro and mentioning

confidence: 99%

Controlling the morphology of copolymeric vectors for next generation nanomedicine

Williams

Pijpers

Ridolfo

et al. 2017

Journal of Controlled Release

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Shape and size-dependent immune response to antigen-carrying nanoparticles

Cited by 263 publications

References 58 publications

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

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

Improving Vaccine and Immunotherapy Design Using Biomaterials

Controlling the morphology of copolymeric vectors for next generation nanomedicine

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