An intranasal vaccine comprising SARS-CoV-2 spike receptor-binding domain protein entrapped in mannose-conjugated chitosan nanoparticle provides protection in hamsters

Abstract

We developed a novel intranasal SARS-CoV-2 subunit vaccine called NARUVAX-C19/Nano based on the spike protein receptor-binding domain (RBD) entrapped in mannose-conjugated chitosan nanoparticles (NP). A toll-like receptor 9 agonist, CpG55.2, was also added as an adjuvant to see if this would potentiate the cellular immune response to the NP vaccine. The NP vaccine was assessed for immunogenicity, protective efficacy, and ability to prevent virus transmission from vaccinated animals to naive cage-mates. The results were compared with a RBD protein vaccine mixed with alum adjuvant and administered intramuscularly. BALB/c mice vaccinated twice intranasally with the NP vaccines exhibited secretory IgA and a pronounced Th1-cell response, not seen with the intramuscular alum-adjuvanted RBD vaccine. NP vaccines protected Syrian hamsters against a wild-type SARS-CoV-2 infection challenge as indicated by significant reductions in weight loss, lung viral load and lung pathology. However, despite significantly reduced viral load in the nasal turbinates and oropharyngeal swabs from NP-vaccinated hamsters, virus transmission was not prevented to naïve cage-mates. In conclusion, intranasal RBD-based NP formulations induced mucosal and Th1-cell mediated immune responses in mice and protected Syrian hamsters against SARS-CoV-2 infection but not against viral transmission.

Chitosan Nanoparticles for Intranasal Drug Delivery

“…SARS-CoV-2 spike RBD protein in mannose-conjugated chitosan nanoparticles Induced robust mucosal and Th1-cell responses, protection against COVID-19; average size: 290 ± 18 nm, uptake rate of RBD protein: 66.8% [37] Chitosan nanoparticles for intranasal delivery of IL-17RC with Interleukin-17 receptor C (IL-17RC)…”

“…Immunogenicity and vaccine development are other crucial areas of testing, requiring the evaluation of immune responses to nanoparticle-based vaccines and comparisons across different administration routes. These studies help determine the efficacy of nanoparticles as vaccine carriers and their ability to elicit desired immune responses [13,29,37,86,89,118,119]. Furthermore, disease-specific testing is vital for targeted therapeutic applications, such as in models of Alzheimer's disease, asthma, schizophrenia, and other conditions.…”

“…Although the intranasal vaccination with these nanoparticles showed protective effects against SARS-CoV-2, it did not prevent viral transmission to naive animals. This indicates that while the vaccine formulation is effective in protecting against the disease, further optimization is needed to prevent transmission [ 37 ]. Hesperidin–chitosan nanoparticles for acute lung injury were developed to enhance the nasal delivery of hesperidin, with the goal of increasing cellular uptake and maximizing anti-inflammatory effects in the lungs.…”

“…Another major area of research is the development of nasal vaccines using chitosan nanoparticles, which seeks to boost immunogenicity and mucosal immunity against pathogens such as influenza, hepatitis, respiratory syncytial virus, pertussis, and SARS-CoV-2 [ 13 , 14 , 17 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. These initiatives reflect the ongoing need for effective vaccination strategies that generate strong immune responses without the need for traditional injection methods.…”

Extraordinary Titer and Broad Anti-SARS-CoV-2 Neutralization Induced by Stabilized RBD Nanoparticles from Strain BA.5

“…Among the approaches to increase breadth and potency, vaccines based on self-assembling nanoparticles appear to be especially promising [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. Such nanoparticle vaccines have multiple advantages.…”