Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines

PLoS Pathogens, Год журнала: 2025, Номер 21(1), С. e1012845 - e1012845

Опубликована: Янв. 8, 2025

Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short vivo exposure. Recent advances extending half-life protein therapeutics have shown promise improving drug efficacy, yet whether increasing persistence can enhance efficacy vaccines remains underexplored. In this study, we developed two trimeric SARS-CoV-2 with distinct pharmacokinetic profiles evaluate impact vaccine on efficacy. A self-assembling (RBD-HR/trimer) was designed, followed by an extended-persistence variant (RBD-sFc-HR/trimer) incorporating a soluble monomeric IgG1 fragment crystallizable. We demonstrated that RBD-sFc-HR/trimer elicited more robust higher levels neutralizing antibodies, potent broad neutralization activity multiple variants. Notably, induced durable response, significantly number memory B cells T cells. This study provides critical insights designing achieve long-lasting responses

Язык: Английский

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Recombinant probiotic Escherichia coli delivers the polymeric protein of swine influenza virus for protection

Veterinary Microbiology, Год журнала: 2025, Номер 302, С. 110401 - 110401

Опубликована: Янв. 21, 2025

Язык: Английский

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Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2

Antiviral Research, Год журнала: 2024, Номер 227, С. 105905 - 105905

Опубликована: Май 11, 2024

Язык: Английский

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Development of Nanoparticle Vaccines Utilizing Designed Fc-Binding Homo-oligomers and RBD-Fc of SARS-CoV-2

Antiviral Research, Год журнала: 2024, Номер 227, С. 105917 - 105917

Опубликована: Май 21, 2024

Язык: Английский

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Protective RBD-dimer vaccines against SARS-CoV-2 and its variants produced in glycoengineered Pichia pastoris

PLoS Pathogens, Год журнала: 2024, Номер 20(8), С. e1012487 - e1012487

Опубликована: Авг. 30, 2024

Protective vaccines are crucial for preventing and controlling coronavirus disease 2019 (COVID-19). Updated needed to confront the continuously evolving circulating severe acute respiratory syndrome 2 (SARS-CoV-2) variants. These should be safe, effective, amenable easily scalable production, affordable. Previously, we developed receptor binding domain (RBD) dimer-based protein subunit (ZF2001 updated vaccines) in mammalian cells. In this study, explored a strategy producing RBD-dimer immunogens Pichia pastoris. We found that wild-type P. pastoris produced hyperglycosylated containing four N-glycosylation sites Therefore, engineered wild type (GS strain) into GSΔOCH1pAO by deleting OCH1 gene (encoding α-1,6-mannosyltransferase enzyme) decrease glycosylation, as well overexpressing HIS4 histidine dehydrogenase) increase synthesis better growth. addition, was truncated remove R328/F329 cleavage Several homogeneous proteins were strain, demonstrating feasibility of using expression system. further resolved cryo-EM structure prototype-Beta complexed with neutralizing antibody CB6 reveal completely exposed immune epitopes RBDs. murine model, demonstrated yeast-produced induces robust protective responses, which is suitable boosting immunization. This study yeast system SARS-CoV-2 immunogens, providing promising platform pipeline future continuous updating production vaccines.

Язык: Английский

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Rabies virus-based oral and inactivated vaccines protect minks against SARS-CoV-2 infection and transmission1

Journal of Integrative Agriculture, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Minks are highly susceptible to SARS-CoV-2, and have transmitted SARS-CoV-2 humans. Oral immunization is one of the most promising strategies prevent infection transmission in minks. Here, we generated three recombinant rabies viruses (RABV), rERAG333E/S6P, rERAG333E/DS6P rERAG333E/BA2S6P, expressing prefusion-stabilized spike protein wild-type (S6P), δ (DS6P) or BA.2 (BA2S6P) strain based on an oral vaccine candidate (rERAG333E). inactivated RABVs monovalent trivalent were safe, induced robust RABV neutralizing antibody cross-antibody responses against mice The challenge tests showed that two doses rERAG333E-S6P as completely protected mouse-adapted upper lower respiratory tracts, largely prevented viral replication lung damage caused by Notably, also confirmed can protect minks via droplets. Our findings suggest rERAG333E-based COVID-19 vaccines appear be suitable candidates from transmission, may serve for further investigation

Язык: Английский

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A Novel Circular Delta‐XBB15 RBD Dimeric Protein Subunit Vaccine Mediated by Split Intein Elicits an Immune Response and Protection Against Multiple SARS‐CoV‐2 Variants in Mice

Journal of Medical Virology, Год журнала: 2024, Номер 96(12)

Опубликована: Дек. 1, 2024

ABSTRACT SARS‐CoV‐2 continues to mutate, leading breakthrough infections. The development of new vaccine strategies combat various strains is crucial. Protein cyclization can enhance thermal stability and may improve immunogenicity. Here, we designed a cyclic tandem dimeric receptor‐binding domain protein (cirRBD2) via the split intein Cth‐Ter. Cyclization does not affect antigen epitopes RBD but results in better than that its linear counterpart (linRBD2). Compared with mice immunized linRBD2, those two doses 5 μg cirRBD2 produced significantly greater levels broad‐spectrum neutralizing antibodies, generated considerable cellular immune response. In VEEV‐VRP‐hACE2‐transduced mouse model, provided protection against infection BA.5, XBB.1.9, partial EG.5 which has more mutations. This study developed novel circular dimer subunit for exhibits activity variants. A similar strategy be applied develop vaccines other pathogens, especially thermally stable vaccines.

Язык: Английский

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Novel and efficient yeast-based strategies for subunit vaccine delivery against COVID-19

International Journal of Biological Macromolecules, Год журнала: 2024, Номер unknown, С. 139254 - 139254

Опубликована: Дек. 1, 2024

Язык: Английский

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