Facile synthesis of multi-faceted, biomimetic and cross-protective nanoparticle-based vaccines for drug-resistant Shigella: a flexible platform technology

Journal of Nanobiotechnology

Research

Nadim Ahamad¹  Namrata Baruah²  Dhirendra S. Katti²  Prolay Halder³  Hemanta Koley³ 

[1]Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, 208016, Kanpur, Uttar Pradesh, India

[2]Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, 208016, Kanpur, Uttar Pradesh, India

[3]The Mehta Family Centre for Engineering in Medicine, Indian Institute of Technology Kanpur, 208016, Kanpur, Uttar Pradesh, India

[4]Division of Bacteriology, ICMR-National Institute of Cholera and Enteric Diseases, 700010, Kolkata, West Bengal, India

关键词: Biomimetic;    Nanoparticle;    Shigella;    Nanovaccine;    Antibiotic resistance;    Shigellosis;    Vaccine;   

DOI  :  10.1186/s12951-023-01780-y

 received in 2022-04-22, accepted in 2023-01-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNo commercial vaccines are available against drug-resistant Shigella due to serotype-specific/narrow-range of protection. Nanoparticle-based biomimetic vaccines involving stable, conserved, immunogenic proteins fabricated using facile chemistries can help formulate a translatable cross-protective Shigella vaccine. Such systems can also negate cold-chain transportation/storage thus overcoming challenges prevalent in various settings.MethodsWe explored facile development of biomimetic poly (lactide-co-glycolide)/PLGA 50:50 based nanovaccines (NVs), encapsulating conserved stabilized antigen(s)/immunostimulant of S. dysenteriae 1 origin surface-modified using simple chemistries. All encapsulants (IpaC/IpaB/LPS) and nanoparticles (NPs)—bare and modified (NV), were thoroughly characterized. Effect of IpaC on cellular uptake of NPs was assessed in-vitro. Immunogenicity of the NVs was assessed in-vivo in BALB/c mice by intranasal immunization. Cross-protective efficacy was assessed by intraperitoneally challenging the immunized groups with a high dose of heterologous S. flexneri 2a and observing for visible diarrhea, weight loss and survival. Passive-protective ability of the simplest NV was assessed in the 5-day old progeny of vaccinated mice.ResultsAll the antigens and immunostimulant to be encapsulated were successfully purified and found to be stable both before and after encapsulation into NPs. The ~ 300 nm sized NPs with a zeta potential of ~ − 25 mV released ~ 60% antigen by 14th day suggesting an appropriate delivery kinetics. The NPs could be successfully surface-modified with IpaC and/or CpG DNA. In vitro experiments revealed that the presence of IpaC can significantly increase cellular uptake of NPs. All NVs were found to be cytocompatible and highly immunogenic. Antibodies in sera of NV-immunized mice could recognize heterologous Shigella. Immunized sera also showed high antibody and cytokine response. The immunized groups were protected from diarrhea and weight loss with ~ 70–80% survival upon heterologous Shigella challenge. The simplest NV showed ~ 88% survival in neonates.ConclusionsFacile formulation of biomimetic NVs can result in significant cross-protection. Further, passive protection in neonates suggest that parental immunization could protect infants, the most vulnerable group in context of Shigella infection. Non-invasive route of vaccination can also lead to greater patient compliance making it amenable for mass-immunization. Overall, our work contributes towards a yet to be reported platform technology for facile development of cross-protective Shigella vaccines.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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