Real‐Time Imaging of Vaccine Biodistribution Using Zwitterionic NIR Nanoparticles

Abstract

Efficient and timely delivery of vaccine antigens to the secondary lymphoid tissue is crucial to induce protective immune responses by vaccination. However, determining the longitudinal biodistribution of injected vaccines in the body has been a challenge. Here, the near‐infrared (NIR) fluorescence imaging is reported that can efficiently enable the trafficking and biodistribution of vaccines in real time. Zwitterionic NIR fluorophores are conjugated on the surface of model vaccines and tracked the fate of bioconjugated vaccines after intradermal administration. Using an NIR fluorescence imaging system, it is possible to obtain time‐course imaging of vaccine trafficking through the lymphatics, observing notable uptake in lymph nodes with minimal nonspecific tissue interactions. Flow cytometry analysis confirmed that the uptake in lymph nodes by antigen presenting cells was highly dependent on the hydrodynamic diameter of vaccines. These results demonstrate that the combination of a real‐time NIR fluorescence imaging system and zwitterionic fluorophores is a powerful tool to determine the fate of vaccine antigens. Since such non‐specific vaccine uptake causes serious adverse reactions, this method is not only useful for optimization of vaccine design, but also for safety evaluation of clinical vaccine candidates.

Mannose-binding lectin and complement mediate follicular localization and enhanced immunogenicity of diverse protein nanoparticle immunogens

“…One important factor is localization of antigens in lymphoid tissues following immunization. Numerous preclinical studies have found that nanoparticles of a variety of compositions drain efficiently through the lymph, but upon reaching secondary lymphoid tissues remain primarily localized within the subcapsular sinus and the medulla or are seemingly excluded from B cell follicles (Katagiri et al, 2019;Manolova et al, 2008;Moon et al, 2012;Mueller et al, 2015;Reddy et al, 2006;Shukla et al, 2017;Wang et al, 2019). Since interactions with B cells within follicles are essential for the development of high-affinity antibodies, localization of antigen within these regions has the potential to drive more robust humoral responses.…”

NIR fluorescence imaging and treatment for cancer immunotherapy

“…65 Katagiri et al reported a real-time trafficking method of a model vaccine labeled with zwitterionic NIR fluorophore ZW800-1C, which enabled the determination of the longitudinal fate of vaccines after intradermal administration (figure 2D). 66 Of note, zwitterionic NIR fluorophores show minimal interactions with biological tissues and do not interfere with the interactions between vaccines and immune cells due to their non-sticky properties resulting from their balanced charges and hydrophilicity. [67][68][69][70][71][72] This combination of zwitterionic NIR fluorophores and NIR imaging can be useful for the optimization of vaccine design as well as the safety evaluation of clinical vaccine candidates.…”

Multimodality imaging of nanoparticle‐based vaccines: Shedding light on immunology

“…Another study which demonstrates the versatility of NIRF imaging as well as the significance of imaging in development and evaluation of a vaccine was carried out by Katagiri et al (2019). This group conjugated a zwitterionic NIR fluorophore, ZW800-1C, on the surface of OVA (OVA-ZW), and subsequently conjugated this to silica nanoparticles of 20 nm (SiNP-20 nm) and 100 nm (SiNP-100 nm) in diameter to form what are referred to as ONP1 and ONP2, respectively.…”

“…The nanovaccine was then evaluated for in vivo biodistribution (Katagiri et al, 2019). Mice were divided into three groups depending on the vaccine formulation they received: ONP1, ONP2, and free OVA-ZW.…”

“…Both (d) and (e) demonstrated that OVA‐ZW had higher uptake in the popliteal lymph nodes for the given time frames. Adapted with permission from Katagiri et al (2019).…”