Protein engineering strategies for rational immunogen design

Caradonna, Timothy M.; Schmidt, Aaron

doi:10.1038/s41541-021-00417-1

Cited by 32 publications

(34 citation statements)

References 223 publications

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“…For a broadly protective vaccine to be created, efforts are needed to understand the molecular aspects of the protective antigen with the effects to magnify the humoral response to the target antigen, reduce 'off-target' antibody responses and, more importantly, augment the response to the target epitopes [171]. In the case of AIV, the common targets for universal influenza vaccine development consist of the highly conserved stalk domain of the HA protein made up of HA1 and HA2, the ectodomain of the M2 ion channel (M2e) and the internal proteins, nucleoprotein (NP) and matrix protein (M1) [172].…”

Section: Designing Vaccines Based On Conserved Regionsmentioning

confidence: 99%

Vaccines against Major Poultry Viral Diseases: Strategies to Improve the Breadth and Protective Efficacy

Rajamanonmani

Chan

Prabakaran

2022

Viruses

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The poultry industry is the largest source of meat and eggs for human consumption worldwide. However, viral outbreaks in farmed stock are a common occurrence and a major source of concern for the industry. Mortality and morbidity resulting from an outbreak can cause significant economic losses with subsequent detrimental impacts on the global food supply chain. Mass vaccination is one of the main strategies for controlling and preventing viral infection in poultry. The development of broadly protective vaccines against avian viral diseases will alleviate selection pressure on field virus strains and simplify vaccination regimens for commercial farms with overall savings in husbandry costs. With the increasing number of emerging and re-emerging viral infectious diseases in the poultry industry, there is an urgent need to understand the strategies for broadening the protective efficacy of the vaccines against distinct viral strains. The current review provides an overview of viral vaccines and vaccination regimens available for common avian viral infections, and strategies for developing safer and more efficacious viral vaccines for poultry.

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Section: Designing Vaccines Based On Conserved Regionsmentioning

confidence: 99%

Vaccines against Major Poultry Viral Diseases: Strategies to Improve the Breadth and Protective Efficacy

Rajamanonmani

Chan

Prabakaran

2022

Viruses

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“…While we only provide a proof-of-concept using the SARS-CoV-2 S protein, our approach can be adopted to fusion proteins of other viruses. Given that prefusion-stabilization is critical for viral immunogen design 50, 59 , our work here should advance the process of viral vaccine development.…”

Section: Discussionmentioning

confidence: 99%

High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike

Tan

Mou

Lei

et al. 2022

Preprint

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Designing prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we established a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrated a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, this method was applied to a region in the S2 domain that includes the first heptad repeat and central helix. Our results revealed that besides K986P and V987P, several mutations simultaneously improved expression and significantly lowered the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.

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“…However, the major drawback is the lower immune response induced by single purified proteins or oligo/polysaccharide components, and consequently fusion proteins with increased size, multiple doses and adjuvants are often required in order to achieve sufficient immunogenicity [74][75][76]. Moreover, the low efficiency of vaccine antigens could be due to immunologically subdominant but protective epitopes [77]. To overcome these issues, self-assembling protein NPs are now widely explored in vaccinology as scaffolds for antigen display [1].…”

Section: Discussionmentioning

confidence: 99%

Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion

Cappelli

Cinelli

Giusti³

et al. 2022

PLoS ONE

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Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants. The use of self-assembling protein nanoparticles, as a platform for vaccine antigen presentation, is emerging as a promising approach to enhance the production of protective and functional antibodies. In this work we demonstrated the successful repetitive antigen display of the C-terminal β-barrel domain of factor H binding protein, derived from serogroup B Meningococcus on the surface of different self-assembling nanoparticles using genetic fusion. Six nanoparticle scaffolds were tested, including viruslike particles with different sizes, geometries, and physicochemical properties. Combining computational and structure-based rational design we were able generate antigen-fused scaffolds that closely aligned with three-dimensional structure predictions. The chimeric nanoparticles were produced as recombinant proteins in Escherichia coli and evaluated for solubility, stability, self-assembly, and antigen accessibility using a variety of biophysical methods. Several scaffolds were identified as being suitable for genetic fusion with the βbarrel from fHbp, including ferritin, a de novo designed aldolase from Thermotoga maritima, encapsulin, CP3 phage coat protein, and the Hepatitis B core antigen. In conclusion, a systematic screening of self-assembling nanoparticles has been applied for the repetitive surface display of a vaccine antigen. This work demonstrates the capacity of rational structurebased design to develop new chimeric nanoparticles and describes a strategy that can be utilized to discover new nanoparticle-based approaches in the search for vaccines against bacterial pathogens.

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Protein engineering strategies for rational immunogen design

Cited by 32 publications

References 223 publications

Vaccines against Major Poultry Viral Diseases: Strategies to Improve the Breadth and Protective Efficacy

Vaccines against Major Poultry Viral Diseases: Strategies to Improve the Breadth and Protective Efficacy

High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike

Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion

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