Co-Administration of Aluminium Hydroxide Nanoparticles and Protective Antigen Domain 4 Encapsulated Non-Ionic Surfactant Vesicles Show Enhanced Immune Response and Superior Protection against Anthrax.

Parveen Sehrawat,Anshu Malik,Himanshu Gogoi,Rajesh Mani,Rakesh Bhatnagar

doi:10.3390/vaccines8040571

Parveen Sehrawat, Anshu Malik + Show 3 more

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https://doi.org/10.3390/vaccines8040571

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Journal: Vaccines	Publication Date: Oct 1, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: Jawaharlal Nehru University, Banaras Hindu University

Abstract

Aluminium salts have been the adjuvant of choice in more than 100 licensed vaccines. Here, we have studied the synergistic effect of aluminium hydroxide nanoparticles (AH np) and non-ionic surfactant-based vesicles (NISV) in modulating the immune response against protective antigen domain 4 (D4) of Bacillus anthracis. NISV was prepared from Span 60 and cholesterol, while AH np was prepared from aluminium chloride and sodium hydroxide. AH np was co-administered with NISV encapsulating D4 (NISV-D4) to formulate AHnp/NISV-D4. The antigen-specific immune response of AHnp/NISV-D4 was compared with that of commercial alhydrogel (alhy) co-administered with NISV-D4 (alhydrogel/NISV-D4), NISV-D4, AHnp/D4, and alhydrogel/D4. Co-administration of NISV-D4 with AH np greatly improved the D4-specific antibody titer as compared to the control groups. Based on IgG isotyping and ex vivo cytokine analysis, AHnp/NISV-D4 generated a balanced Th1/Th2 response. Furthermore, AH np/NISV-D4 showed superior protection against anthrax spore challenge in comparison to other groups. Thus, we demonstrate the possibility of developing a novel combinatorial nanoformulation capable of augmenting both humoral and cellular response, paving the way for adjuvant research.

Highlights

Since Edward Jenner’s discovery of the first vaccine against smallpox, vaccines have brought a revolution in the medical world
When we evaluated the cytokine profile elicited by the co-administration of the AHnp/non-ionic surfactant-based vesicles (NISV)-domain 4 (D4), we observed a substantial increase in the levels of Th1 cytokines IL-2, IFN-γ, and TNF-α (Figure 4a–c), when we compare with AH
Of attention, duethe to their enhanced uptake efficacy nanoparticle-based by antigen-presenting cells, ease of received a great amount of attention, due to their enhanced uptake efficacy by antigen-presenting engineering physicochemical properties, and targeted delivery [11,42,43]

Summary

Introduction

Since Edward Jenner’s discovery of the first vaccine against smallpox, vaccines have brought a revolution in the medical world. Their use has resulted in a huge economic and social impact, by lowering disease burden and increasing life expectancy in a cost-effective manner. To elicit a desired immune response, a vaccine often requires the inclusion of an adjuvant, which enhances the innate immune mechanism. The adjuvant assists with directing the specificity of an immune response [1,2]. Aluminium salts have been the choice of an adjuvant since 1926 after Glenny demonstrated the potential of alum-precipitated diphtheria toxoid to enhance the antibody production [3]. The family of aluminium adjuvant comprises of aluminium hydroxide, aluminium phosphate, and potassium aluminium sulphate/alum

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Conclusion