Technological challenges in the preclinical development of an HIV nanovaccine candidate

Abstract

Despite a very active research in the field of nanomedicine, only a few nano-based drug delivery systems have reached the market. The "death valley" between research and commercialization has been partially attributed to the limited characterization and reproducibility of the nanoformulations.Our group has previously reported the potential of a peptide-based nanovaccine candidate for the prevention of SIV infection in macaques. This vaccine candidate is composed of chitosan/dextran sulfate nanoparticles containing twelve SIV peptide antigens. The aim of this work was to rigorously characterize one of these nanoformulations containing a specific peptide, following a quality-by-design approach. The evaluation of the different quality attributes was performed by several complementary techniques, such as dynamic light scattering, nanoparticle tracking analysis and electron microscopy for particle size characterization. The inter-batch reproducibility was validated by three independent laboratories. Finally, the long-term stability and scalability of the manufacturing technique were assessed. Overall, these data, together with the in vivo efficacy results obtained in macaques, underline the promise this new vaccine holds with regard to its translation to clinical trials.

Carboxymethyl-β-glucan/chitosan nanoparticles: new thermostable and efficient carriers for antigen delivery

“…Results showed the particle size and polydispersity index of the formulations was maintained in these conditions (supplementary Fig. 3), in accordance with previous works from our group showing that, when formulated in optimal conditions, polymeric antigen nanocarriers can be stable for long periods of time [14,17,46,47].…”

“…The selected beta glucan derivative was recently evaluated by our group as a coating in polymeric nanocapsules, which have shown promising biodistribution to the lymphatic system and high accumulation in lymph nodes following subcutaneous administration to mice [37]. On the other hand, the adjuvant potential of chitosan, particularly when used in the form of nanoparticles, was first demonstrated by our group in the late 90s [38] and has been since explored in the group for immunization against various infectious agents [12,[14][15][16][17].…”

“…Among these, chitosan (CS) has played a significant role in this field. For example, our group has shown the potential of CS-based nanocarriers for antigen delivery, generating high and long-lasting immune responses in animal models against encapsulated antigens such as tetanus toxoid, rHBsAg, and a candidate vaccine against HIV [12][13][14][15][16][17].…”

Injectable Hydrogels: From Laboratory to Industrialization

“…The purpose of a QdB is to assess how the formulation of the injectable hydrogel and the fabrication parameters influence the characteristics of the formulation. QdB involves the definition of a quality target product profile (QTTP) and the critical quality attributes (CQAs) of the formulation [78]. QTTP refers to parameters of the product such as indication, route of administration, dosage form, packaging, stability, dispersibility and moisture, while CQAs relates to components, contents uniformity, water content, microbial content, and physicochemical properties (pH, osmolality).…”

Advances in vaccine delivery systems against viral infectious diseases

“…For clinical translation, the manufacturing process and physical stability of nanomaterial-based vaccines should be studied during the development phase [87]. Given the limitation of worldwide cold chains, the stability of vaccine candidates under humid and hot conditions should be studied.…”