A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses

Matondo, Sungwa; Thrane, Susan; Janitzek, Christoph M.; Adolph, Kavishe Reginald; Boniface, Mwakalinga Steven; Theander, Thor G.; Salanti, Ali; Nielsen, Morten A.; Frederik, Sander Adam

doi:10.4314/ahs.v17i2.11

Cited by 7 publications

(3 citation statements)

References 22 publications

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“…Although it is well-documented that the isopeptide bond formation between SpyTag and SpyCatcher is robust and reliable, ,,− conjugation of the SC-CBU1910 antigen onto the surface to ST-E2 required optimization to yield intact and monodisperse nanoparticles. As seen with other ST/SC VLP formulations, adjustments to reaction molar ratios, pH, ionic strength, and/or detergent concentrations were required to prevent precipitation/aggregation. ,− A tabulated list of the optimization conditions and solubilizing additives (i.e., surfactants, buffers, and salts) can be found in Figure SI-5. From our investigation, we determined favorable reaction conditions to be a 1:0.5 molar ratio of ST-E2 (monomer):SC-CBU1910 at room temperature for 20 h with the addition of 0.08–0.0875% (w/v) SLS; this resulted in stable, monodisperse nanoparticles (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine

Ramirez,

Felgner,

Jain

et al. 2023

Bioconjugate Chem.

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Coxiella burnetii is the causative agent of Q fever, for which there is yet to be an FDA-approved vaccine. This bacterial pathogen has both extra- and intracellular stages in its life cycle, and therefore both a cell-mediated (i.e., T lymphocyte) and humoral (i.e., antibody) immune response are necessary for effective eradication of this pathogen. However, most proposed vaccines elicit strong responses to only one mechanism of adaptive immunity, and some can either cause reactogenicity or lack sufficient immunogenicity. In this work, we aim to apply a nanoparticle-based platform toward producing both antibody and T cell immune responses against C. burnetii. We investigated three approaches for conjugation of the immunodominant outer membrane protein antigen (CBU1910) to the E2 nanoparticle to obtain a consistent antigen orientation: direct genetic fusion, high affinity tris-NTA-Ni conjugation to polyhistidine-tagged CBU1910, and the SpyTag/SpyCatcher (ST/SC) system. Overall, we found that the ST/SC approach yielded nanoparticles loaded with the highest number of antigens while maintaining stability, enabling formulations that could simultaneously co-deliver the protein antigen (CBU1910) and adjuvant (CpG1826) on one nanoparticle (CBU1910-CpG-E2). Using protein microarray analyses, we found that after immunization, antigen-bound nanoparticle formulations elicited significantly higher antigen-specific IgG responses than soluble CBU1910 alone and produced more balanced IgG1/IgG2c ratios. Although T cell recall assays from these protein antigen formulations did not show significant increases in antigen-specific IFN-γ production compared to soluble CBU1910 alone, nanoparticles conjugated with a CD4 peptide epitope from CBU1910 generated elevated T cell responses in mice to both the CBU1910 peptide epitope and whole CBU1910 protein. These investigations highlight the feasibility of conjugating antigens to nanoparticles for tuning and improving both humoral- and cell-mediated adaptive immunity against C. burnetii.

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Section: Resultsmentioning

confidence: 99%

Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine

Ramirez,

Felgner,

Jain

et al. 2023

Bioconjugate Chem.

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“…To change the displayed antigen, a new protein is expressed recombinantly with the appropriate SpyTag and linked to the desired VLP. There are several VLP variants, which have been improved by mutagenesis or computationally, such as SpyCatcher003-mi3 [ 54 , 55 , 56 ], and they have been used successfully to produce vaccine prototypes against malaria, influenza, and more recently SARS-CoV-2 [ 57 , 58 ].…”

Section: Use Of Virus-like Particles As a Vaccination Strategymentioning

confidence: 99%

The Potential of Plant-Produced Virus-like Particle Vaccines for African Horse Sickness and Other Equine Orbiviruses

Pitchers,

Boakye,

Campeotto

et al. 2024

Pathogens

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African horse sickness is a devastating viral disease of equids. It is transmitted by biting midges of the genus Culicoides with mortalities reaching over 90% in naïve horses. It is endemic to sub-Saharan Africa and is seasonally endemic in many parts of southern Africa. However, outbreaks in Europe and Asia have occurred that caused significant economic issues. There are attenuated vaccines available for control of the virus but concerns regarding the safety and efficacy means that alternatives are sought. One promising alternative is the use of virus-like particles in vaccine preparations, which have the potential to be safer and more efficacious as vaccines against African horse sickness. These particles are best made in a complex, eukaryotic system, but due to technical challenges, this may cause significant economic strain on the developing countries most affected by the disease. Therefore, this review also summarises the success so far, and potential, of recombinant protein expression in plants to reduce the economic strain of production.

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“…Additionally, var2csa gene occur more in infected placentae than in samples of P. falciparum from non-pregnant women [50]. Therefore developing vaccine that targets VSAPAM antigen could hold promises against LBW, spontaneous abortion, preterm labour and stillbirth caused by PAM [46,51].…”

Section: Immunity In Pammentioning

confidence: 99%

Pregnancy-associated Malaria, Challenges and Prospects in Sub-Saharan Africa

Aguzie¹

2018

Clinics Mother Child Health

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Pregnancy-associated malaria remains a major risk to the pregnant woman, her foetus and infants in sub-Saharan Africa. Infection by Plasmodium falciparum significantly affects maternal, foetal and neonatal wellbeing. Maternal anaemia, low birth weight, preterm labour, spontaneous abortion, and maternal and neonatal mortalities are some of its consequences. It complicates maternal immunological responses and possibly also selfishly preempts foetal immunological responses by transplacental communications. Therefore, the impacts may extend well beyond the duration of pregnancy and the immediate period post-delivery. Effective case management and prevention continue to yield positive results, but challenges still remains especially in sub-Saharan Africa. The challenges of antenatal service provision, compliance with intermittent preventive treatment at pregnancy with sulfadoxine-pyrimethamine (IPTp-SP), widespread SP resistance, and resistance to insecticide treated nets (ITNs) and insecticides continue to complicate efforts at PAM control in sub-Saharan Africa. Hopefully, the Global Technical Strategy for Malaria 2016-2030 will comprehensively consider these challenges and improve the prospect of every pregnant woman in sub-Saharan Africa.

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A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses

Cited by 7 publications

References 22 publications

Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine

Engineering Protein Nanoparticles Functionalized with an Immunodominant Coxiella burnetii Antigen to Generate a Q Fever Vaccine

The Potential of Plant-Produced Virus-like Particle Vaccines for African Horse Sickness and Other Equine Orbiviruses

Pregnancy-associated Malaria, Challenges and Prospects in Sub-Saharan Africa

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