Nano-microparticles as immune adjuvants: correlating particle sizes and the resultant immune responses

Abstract

The development of novel immune adjuvants is emerging as a significant area of vaccine delivery based on the continued necessity to amplify immune responses to a wide array of new antigens that are poorly immunogenic. This article specifically focuses on the application of nanoparticles and microparticles as vaccine adjuvants. Many investigators are in agreement that the size of the particles is crucial to their adjuvant activities. However, reports on correlating the size of particle-based adjuvants and the resultant immune responses have been conflicting, with investigators on both sides of the fence with impressive data in support of the effectiveness of particles with small sizes (submicron) over those with larger sizes (micron) and vice versa, while other investigators reported data that showed submicron- and micron-sized particles are effective to the same degree as immune adjuvants. We have generated a list of biological, immunological and, more importantly, vaccine formulation parameters that may have contributed to the inconsistency from different studies and made recommendations on future studies attempting to correlate the size of particulate adjuvants and the immune responses induced. The information gathered could lead to strategies to optimize the performance of nano-microparticles as immune adjuvants.

A therapeutic nanoparticle vaccine againstTrypanosoma cruziin a BALB/c mouse model of Chagas disease

“…Our findings here are similar to our previous observations using this adjuvant and delivery system with a model antigen (ovalbumin). 37 They are also consistent with reported studies showing T H 1-biased enhancement of other protein antigens when combined with CpG ODN in PLGA nanoparticles. [48][49][50] Other therapeutic vaccines against Chagas disease have been found to induce a protective antigen-specific CD8 C T cell population that expands upon challenge with infection and produces T H 1-associated cytokines that include IFNg and TNFa, 51 as well as a CD4 C T cell population capable of IFNg production.…”

“…therapeutic efficacy in mice will be translatable to humans, additional studies in non-human primates will be needed before moving the vaccine to the clinic. Lastly, while the PLGA nanoparticle production method employed in this paper is a common method that has been previously published, 37 debate exists as to the ideal size of nanoparticles for vaccine delivery. Some reports suggest that "viral-size" nanoparticles may enhance the immune response, while other studies report that larger particles elicit a better immune response.…”

“…35 Nanoparticles can also serve as a depot for antigen, 36 allowing prolonged stimulation of the T H 1 pathway. 37 A common polymer used in nanoparticle synthesis is poly(lactic-co-glycolic acid) (PLGA). 38 PLGA is biocompatible and biodegradable.…”

Multiantigenic peptide–polymer conjugates as therapeutic vaccines against cervical cancer

“…14 However, it has been reported that very large-sized particles ranging from 50-100 m (which is larger than a typical APC) were least likely to be taken up by APCs, resulting in the generation of a low immune response. 31 Conjugates 6 and 7 formed large microparticles (143 µm and 106 µm, respectively), while construct 5 formed large, highly polydisperse aggregates (laser diffraction could not determine their sizes). Therefore, limited improvement in the efficacy upon incorporation of the E6 epitope into polymer-based vaccine might be related to the hydrophobic properties of the epitope, which cause extensive aggregation of the conjugates bearing it.…”

“…30, 31,32 Large particles usually have an efficient depot effect for continuous antigen release. 31,33 We have proven that polyacrylate polymers conjugated to the E7 epitope formed microparticles (12-17 m), which were able to be efficiently taken up by APCs (including macrophages and dendritic cells), as well as to activate CD8 + and CD4 + cells to elicit adequate cellular immune responses against E7-expressing tumors. 14 However, it has been reported that very large-sized particles ranging from 50-100 m (which is larger than a typical APC) were least likely to be taken up by APCs, resulting in the generation of a low immune response.…”