RBD decorated PLA nanoparticle admixture with aluminum hydroxide elicit robust and long lasting immune response against SARS-CoV-2

Meena, Jairam; Singhvi, Priyank; Srichandan, Sudeepa; Dandotiya, Jyotsna; Verma, Juhi; MamtaSingh,; Ahuja, Rahul; Panwar, Neha; Wani, Tabiya Qayoom; Khatri, Ritika; Siddiqui, Gazala; Gupta, A.; Samal, Sweety; Panda, Amulya K.

doi:10.1016/j.ejpb.2022.05.008

Cited by 9 publications

(7 citation statements)

References 30 publications

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“…Recombinant RBD was purified as described earlier 15 . The sequence of purified RBD protein was analyzed by mass spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

“…The protein was purified according as described previously from E. coli and subsequently characterized 15 . RBD was resolved on SDS-PAGE and in gel digestion was performed to prepare the sample for mass spectrometry.…”

Section: Methodsmentioning

confidence: 99%

“…Particles made of synthetic polymers like PLA and PLGA are the most favourable antigen delivery vehicle. These biodegradable polymers poly lactic acid (PLA) or poly lactide-co-glycolides (PLGA) have medically been in use as suture materials and diverse controlled release formulations 13 , 14 , 15 .…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity Evaluation of Thermostable Microparticles Entrapping Receptor Binding Domain of SARS-CoV-2 by Single Point Administration

Ahuja

Srichandan

Meena

et al. 2023

Journal of Pharmaceutical Sciences

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“…Recombinant RBD was purified as described earlier 15 . The sequence of purified RBD protein was analyzed by mass spectroscopy.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Immunogenicity Evaluation of Thermostable Microparticles Entrapping Receptor Binding Domain of SARS-CoV-2 by Single Point Administration

Ahuja

Srichandan

Meena

et al. 2023

Journal of Pharmaceutical Sciences

Self Cite

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“…After solubilization and renaturalization, they recovered 65.2% of the produced RBD by Nickel affinity chromatography, reporting a production yield of 13.3 mg/L. Meena et al [84] also informed RBD production in bacterial cells as inclusion bodies. These authors cultivated a E. coli strain carrying the RBD gene in Erlenmeyer flask containing 1 L of a complex not defined media (a modification of the Luria Bertani broth), ampicillin and IPTG induction.…”

Section: Discussionmentioning

confidence: 99%

Development of a Cost-Effective Process for the Heterologous Production of SARS-CoV-2 Spike Receptor Binding Domain (RBD) Using Pichia pastoris in Stirred-Tank Bioreactor

Noseda¹,

D’Alessio²,

Santos³

et al. 2023

Preprint

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SARS-CoV-2 was identified as the pathogenic agent causing the COVID-19 pandemic. Among the proteins codified by this virus, the Spike is one of the most external and exposed. A fragment of the Spike protein, named the Receptor Binding Protein (RBD) interacts with the ACE2 receptors of human cells, allowing the entrance of the viruses. RBD has been proposed as an interesting protein for the development of diagnosis tools, treatment and prevention of the disease. In this work, a method for recombinant RBD production using Pichia pastoris as a cell factory in a Stirred Tank Bioreactor (SRTB) up to 7 L was developed. Using a basal saline medium with glycerol, methanol and compressed air in a four stages procedure, around 500 mg/L of raw yRBD (RBD produced by yeasts) and 206 mg/L of purified (>95%) RBD were obtained. Thereby, the proposed method represents a feasible, simple, scalable and cheap procedure for the obtention of RBD for diagnosis kits and vaccines formulation

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Wang,

Zhang,

et al. 2023

Vaccines

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The receptor-binding domain (RBD) of the SARS-CoV-2 spike is a primary target of neutralizing antibodies and a key component of licensed vaccines. Substantial mutations in RBD, however, enable current variants to escape immunogenicity generated by vaccination with the ancestral (WA1) strain. Here, we produce and assess self-assembling nanoparticles displaying RBDs from WA1 and BA.5 strains by using the SpyTag:SpyCatcher system for coupling. We observed both WA1- and BA.5-RBD nanoparticles to degrade substantially after a few days at 37 °C. Incorporation of nine RBD-stabilizing mutations, however, increased yield ~five-fold and stability such that more than 50% of either the WA1- or BA.5-RBD nanoparticle was retained after one week at 37 °C. Murine immunizations revealed that the stabilized RBD-nanoparticles induced ~100-fold higher autologous neutralization titers than the prefusion-stabilized (S2P) spike at a 2 μg dose. Even at a 25-fold lower dose where S2P-induced neutralization titers were below the detection limit, the stabilized BA.5-RBD nanoparticle induced homologous titers of 12,795 ID50 and heterologous titers against WA1 of 1767 ID50. Assessment against a panel of β-coronavirus variants revealed both the stabilized BA.5-RBD nanoparticle and the stabilized WA1-BA.5-(mosaic)-RBD nanoparticle to elicit much higher neutralization breadth than the stabilized WA1-RBD nanoparticle. The extraordinary titer and high neutralization breadth elicited by stabilized RBD nanoparticles from strain BA.5 make them strong candidates for next-generation COVID-19 vaccines.

show abstract

RBD decorated PLA nanoparticle admixture with aluminum hydroxide elicit robust and long lasting immune response against SARS-CoV-2

Cited by 9 publications

References 30 publications

Immunogenicity Evaluation of Thermostable Microparticles Entrapping Receptor Binding Domain of SARS-CoV-2 by Single Point Administration

Immunogenicity Evaluation of Thermostable Microparticles Entrapping Receptor Binding Domain of SARS-CoV-2 by Single Point Administration

Development of a Cost-Effective Process for the Heterologous Production of SARS-CoV-2 Spike Receptor Binding Domain (RBD) Using Pichia pastoris in Stirred-Tank Bioreactor

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

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