Vaccination is a key component of public health policy with demonstrated cost-effective benefits in protecting both human and animal populations. Vaccines can be manufactured under multiple forms including, inactivated (killed), toxoid, live attenuated, Virus-like Particles, synthetic peptide, polysaccharide, polysaccharide conjugate (glycoconjugate), viral vectored (vector-based), nucleic acids (DNA and mRNA) and bacterial vector/synthetic antigen presenting cells. Several processes are used in the manufacturing of vaccines and recent developments in medical/biomedical engineering, biology, immunology, and vaccinology have led to the emergence of innovative nucleic acid vaccines, a novel category added to conventional and subunit vaccines. In this review, we have summarized recent advances in vaccine technologies and platforms focusing on their mechanisms of action, advantages, and possible drawbacks.

Chitosan shows effective nucleic acid delivery. To understand the influence of chitosan’s molecular weight, dose, payload, and hyaluronic acid coating on in vivo toxicity, immune stimulation, biodistribution and efficacy, precisely characterized chitosans were formulated with unmodified or chemically modified siRNA to control for innate immune stimulation. The hemocompatibility, cytokine induction, hematological and serological responses were assessed. Body weight, clinical signs, in vivo biodistribution and functional target knockdown were monitored. Hemolysis was found to be dose- and MW-dependent with the HA coating abrogating hemolysis. Compared to cationic lipid nanoparticles, uncoated and HA-coated chitosan nanoparticles did not induce immune stimulation or hematologic toxicity. Liver and kidney biomarkers remained unchanged with chitosan formulations, while high doses of cationic lipid nanoparticles led to increased transaminase levels and a decrease in body weight. Uncoated and HA-coated nanoparticles accumulated in kidneys with functional knockdown for uncoated chitosan formulations reaching 60%, suggesting potential applications in the treatment of kidney diseases.

Background: Chitosan, a family of polysaccharides composed of glucosamine and N-acetyl glucosamine, is a promising adjuvant candidate for eliciting potent immune response. Methods: This study compared the adjuvant effects of chitosan to those of empty lipid nanoparticles (eLNPs) and aluminum hydroxide (alum) following administration of recombinant SARS-CoV-2 spike immunogen in adult mice. Mice received the adjuvanted recombinant protein vaccine in a prime-boost regimen with four weeks interval. Subsequent analyses included serological assessment of antibody responses, evaluation of T cell activity, immune cell recruitment and cytokine profiles at injection site. Results: Compared to alum, chitosan induced a more balanced Th1/Th2 response, akin to that observed with eLNPs, demonstrating its ability to modulate both the humoral and cellular immune pathways. Chitosan induced a different proinflammatory cytokine (e.g., IL-1⍺, IL-2, IL-6, and IL-7) and chemokine (e.g., Eotaxin, IP-10, MIP-1a) profile compared to eLNPs and alum at the injection site and in the draining lymph nodes. Moreover, chitosan potentiated the recruitment of innate immune cells, with neutrophils accounting for about 40% of the infiltrating cells in the muscle, representing a ~10-fold increase compared to alum and a comparable level to eLNPs. Conclusions: These findings collectively indicate that chitosan has the potential to serve as an effective adjuvant, offering comparable, and potentially superior, properties to those of currently approved adjuvants.