Background and Purpose: Rabies virus is a fatal infectious disease in the mammalian host including humans, carnivores, and livestock which imposes a huge burden on the health of the community and the global economy. The development of new rabies vaccines is a critical step for controlling the disease; however, a safe, cheap, and effective vaccine against the disease remains unaffordable in developing countries.
Nowadays, aluminum oxide (Alum) is used to improve the efficacy of rabies vaccines. However, alum improves immune responses, but some of its disadvantages limited its application in the formulation of the vaccine. Therefore, new adjuvants with low side effects, long-term immune stimulation, and simultaneous stimulation of humoral, cellular, and mucosal responses are necessary to increase the immunity of weakened antigens. Recent advances in the field of nanotechnology, especially in the production of the size and shape of metal nanoparticles, lead to the development of various types of applications. Cerium metal, with its special properties, especially low toxicity, has a unique ability to stimulate the immune system as an adjuvant. Given the above, the aim of the current study is adjuvanticity evaluation of cerium nanoparticles in veterinary rabies vaccine to use it to increase the potency rate of the vaccine.
Methods: Aqueous cerium nitrate was used for purification by sonification to synthesize cerium nanoparticles. Then we used X-ray and electron microscopy to confirm the nature of synthetic nanoparticles. In the next section, we examined in vitro toxicity, adjuvanticity and immunogenic properties, the eliciting of neutralizing antibodies, and the production of interleukin-4. Synthesized CeNPs were confirmed through XRD, SEM, and TEM analysis.
Results: The prepared CeNPs were spherical with a diameter of less than 50 nm. As determined by the dynamic light scattering method, the zeta potential was 26.6 mV. No significant cytotoxic effects were observed at any of the tested concentrations. The neutralizing antibodies (NAbs) measured by the RFFIT method in the fourth group (killed virus formulated with CeNPs) also had a statistically significant difference compared to the negative control groups (P≤0.01). There was no significant difference in the level of interleukin-4 in the CeNPs group compared to the negative control groups (P≥0.05).
Conclusions: The data showed that cerium nanoparticles have adjuvant properties in the rabies virus vaccine. In this regard, it seems that more studies are needed on the adjuvant property of metal nanoparticles, especially cerium, and their effect on the production of neutralizing antibodies by using them as carriers of the rabies virus nucleoprotein.
Key Words: rabies virus, cerium nanoparticles, Adjuvant
Audience take away:
- The present study has shown that cerium nanoparticles in the rabies virus vaccine have adjuvant properties.
- In this context, it seems that further studies are needed on the adjuvant properties of metal nanoparticles, especially cerium, and their effect on the production of neutralizing antibodies by using them as carriers of rabies virus nucleoprotein.