Liposomal Dual Delivery of Both Polysaccharide and Protein Antigens

Nayerhoda, Roozbeh; Hill, Andrew

doi:10.1007/978-1-0716-0795-4_26

Cited by 4 publications

(6 citation statements)

References 13 publications

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“…Recombinant production of the PncO protein antigen was accomplished as reported previously ( Jones et al, 2017 ; Hill et al, 2018 ; Nayerhoda et al, 2019 ; Nayerhoda et al, 2021 ). Briefly, Escherichia coli strain BL21(DE3) containing a plasmid with the PncO gene was grown in lysogeny broth (LB) medium with ampicillin (100 μM) while shaking overnight at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection

et al. 2021

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Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts older adults aged ≥65 years. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2–3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (18–22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

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Section: Methodsmentioning

confidence: 99%

“…LEPS formulation and assessment was completed as previously reported ( Jones et al, 2017 ; Hill et al, 2018 ; Nayerhoda et al, 2019 ; Nayerhoda et al, 2021 ). Briefly, all lipids were purchased from Avanti, Thermo Fisher, or Sigma Aldrich, and pneumococcal polysaccharides serotype 19F and 4 were obtained from ATCC.…”

Section: Methodsmentioning

confidence: 99%

Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection

et al. 2021

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“…Recombinant production of the PncO protein antigen was accomplished as reported previously (24, 25, 28, 29). Briefly, Escherichia coli strain BL21(DE3) containing a plasmid with the PncO gene was grown in lysogeny broth (LB) medium with ampicillin (100 μM) while shaking overnight at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…LEPS formulation and assessment was completed as previously reported (24, 25, 28, 29). Briefly, all lipids were purchased from Avanti, Thermo Fisher, or Sigma Aldrich, and pneumococcal polysaccharides serotype 19F and 4 were obtained from ATCC.…”

Section: Methodsmentioning

confidence: 99%

Liposomal encapsulation of polysaccharides (LEPS) as an effective vaccine strategy to protect aged hosts against S. pneumoniae infection

Bhalla

Nayerhoda

Tchalla

et al. 2021

Preprint

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Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts elderly individuals ≥65 years old. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2-3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (20-22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.

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“…The non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), is an immunogenic carrier protein that was chemically conjugated to poly-/oligo-saccharide-based antigens and approved by regulators as conjugate vaccine for prevention of infectious diseases such as Streptococcus pneumoniae or Small 2022, 2205819 While numerous antigen formulations using particle technologies such as liposomes, [8] lipid nanodiscs, [9] poly(lactic-coglycolic acid) (PLGA), [7b] polyhydroxyalkanoates (PHA), [7a] polymersomes, [10] and emulsions, [11] were investigated, they are based on empirical approaches for incorporation of individual antigens.…”

Section: Introductionmentioning

confidence: 99%

Assembly of Immunogenic Protein Particles toward Advanced Synthetic Vaccines

Chen

Quan

Sam

et al. 2022

Small

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Haemophilus influenza type b. [1] Chemical conjugation to CRM197 renders poly-/ oligo-saccharides immunogenic. [2] Poorly immunogenic peptides were also conjugated to CRM197 and became immunogenic. [3] However, conjugate vaccines are one of the most expensive vaccine types as they require laborious manufacture of pure recombinant CRM197 and pure polysaccharide or peptide followed by chemical conjugation and by removal of conjugation chemicals. [2,4] It should be noted that conjugate vaccine formulations include adjuvants to further enhance immunogenicity.Soluble protein antigens are safe but poorly immunogenic and require formulation with adjuvants to boost immunogenicity. [5] Such subunit vaccines composed of soluble protein antigens were approved to prevent such as, for example, whooping cough. Only a few adjuvants including aluminium hydroxide, MF59, and AS01 have been approved for use in vaccine formulations and there are concerns of adverse reaction caused by adjuvants. [6] Another but still experimental approach is formulation of soluble antigens into particles, which further enhances immunogenicity due to facilitated uptake by antigen-presenting cells (APCs), which activate T cell immune responses essential for protection against intracellular pathogens such as viruses and some bacteria (e.g., Mycobacterium tuberculosis). [7] Immunogenic carrier proteins such as the non-toxic diphtheria toxin variant, cross-reacting material 197 (CRM197), are widely used in subunit vaccine formulations to boost immunogenicity of chemically conjugated antigens. Conjugate vaccines are inherently expensive due to laborious manufacturing steps. Here, this work develops a particulate vaccine platform based on using engineered Escherichia coli to assemble CRM197-antigen fusion proteins into discrete submicron-sized particles. This approach enables precise loading of diverse antigens and epitopes enhancing their immunogenicity. A costeffective, high-yield, and scalable biomanufacturing process is developed. Purified particulate CRM197-antigen vaccines are ambient-temperature stable. CRM197 particles incorporating pathogen-specific antigens or epitopes from SARS-CoV-2, Streptococcus pyogenes (group A), and Mycobacterium tuberculosis induced cell-mediated and humoral immune responses mediating protective immunity in respective animal models of infection. The CRM197 particle vaccine platform is versatile, enabling co-delivery of selected antigens/epitopes together with immunogenic CRM197 as discrete stable particles avoiding laborious manufacture of soluble CRM197 and antigen followed by chemical conjugation.

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Liposomal Dual Delivery of Both Polysaccharide and Protein Antigens

Cited by 4 publications

References 13 publications

Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection

Liposomal Encapsulation of Polysaccharides (LEPS) as an Effective Vaccine Strategy to Protect Aged Hosts Against S. pneumoniae Infection

Liposomal encapsulation of polysaccharides (LEPS) as an effective vaccine strategy to protect aged hosts against S. pneumoniae infection

Assembly of Immunogenic Protein Particles toward Advanced Synthetic Vaccines

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