Cross-linked protein crystals for vaccine delivery

Abstract

The progress toward subunit vaccines has been limited by their poor immunogenicity and limited stability. To enhance the immune response, subunit vaccines universally require improved adjuvants and delivery vehicles. In the present paper, we propose the use of cross-linked protein crystals (CLPCs) as antigens. We compare the immunogenicity of CLPCs of human serum albumin with that of soluble protein and conclude that there are marked differences in the immune response to the different forms of human serum albumin. Relative to the soluble protein, crystalline forms induce and sustain over almost a 6-month study a 6-to 10-fold increase in antibody titer for highly cross-linked crystals and an approximately 30-fold increase for lightly cross-linked crystals. We hypothesize that the depot effect, the particulate structure of CLPCs, and highly repetitive nature of protein crystals may play roles in the enhanced production of circulating antibodies. Several features of CLPCs, such as their remarkable stability, purity, biodegradability, and ease of manufacturing, make them highly attractive for vaccine formulations. This work paves the way for a systematic study of protein crystallinity and cross-linking on enhancement of humoral and T cell responses.

Sustained Expression of Human Cytomegalovirus Glycoprotein B (UL55) in the Seeds of Homozygous Rice Plants

“…The use of seeds for directed, tissue-specific subunit vaccine production offers several potential advantages. First, particulate antigens are known to induce a stronger immune response than soluble proteins, regardless of immunization route [39,40]. Data from studies with recombinant subunit vaccines delivered in plant seeds that were either whole, crudely ground, or otherwise minimally processed have confirmed that this general principle applies equally to plant-derived vaccines [41][42][43][44][45].…”

NSOM‐ and AFM‐based nanotechnology elucidates nano‐structural and atomic‐force features of a Y. pestis V immunogen‐containing particle vaccine capable of eliciting robust response

“…Thus, the NSOM/QD-based nanoscale proteomic analysis would not overestimate V-PA immunogen loading, but allows us to conclude that high-density V-PA immunogen nanoclusters were loaded on the surface of GEM vaccine particle. It is also worth to point out that high-density of immunogen nanoclusters loaded on particle surface may be one of the important immune features of a highly immunogenic particle vaccine as a large amount of immunogen could be readily exposed to the immune system for eliciting robust immune responses [33, 34]. …”

Cross-linked protein crystals by glutaraldehyde and their applications

“…Burroughs et al 112 reported the immunogenicity of protein crystals and Clair et al 113 concluded that the immunogenicity of cross-linked human serum albumin crystals was better than that of soluble proteins. Burroughs et al 112 reported the immunogenicity of protein crystals and Clair et al 113 concluded that the immunogenicity of cross-linked human serum albumin crystals was better than that of soluble proteins.…”