High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity

Sun, Xin; Wang, Yunlong; Dong, Caiwen; Hu, Jinqiang; Yang, Liping

doi:10.5582/bst.2015.01060

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…Although phages T7 and fd have also been used as carriers to present M2e, they induced limited protections [31,49]. This probably because they cannot present full-length M2e in high density, which is the key determinant of immune responses induced by M2e-based vaccines [50]. We showed that ~427 copies of the 21.8 kDa Soc-3M2e containing three tandem copies of M2e from human, swine, and avian influenza viruses were assembled on each T4 capsid.…”

Section: Discussionmentioning

confidence: 91%

Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

Guo

Chen

et al. 2021

Preprint

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Developing influenza vaccines that protect against a broad range of viruses is a public health priority, and several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is immunogenic, and vaccine platforms that can incorporate multiple antigens with enhanced immunogenicity are desperately needed. In this study, we provided proof-of-concept for the development of next-generation influenza vaccine using T4 phage virus-like particle (VLP) platform. With extracellular domain of influenza matrix protein 2 (M2e) as a readout, we showed that more than 1,280 M2e molecules can be assembled on a 120×90 nanometer phage capsid to form T4-M2e VLPs, which are highly immunogenic and induced complete protection against influenza virus challenge without any addition adjuvant. Potentially, additional conserved antigens or molecular adjuvants could be incorporated into the T4-M2e VLPs to customize influenza vaccines to address different issues. All the components of T4 VLP vaccines can be mass-produced in E. coli in a short time, therefore, providing a rapid approach to deal with the potential influenza pandemic.

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Section: Discussionmentioning

confidence: 91%

Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

Guo

Chen

et al. 2021

Preprint

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show abstract

“…Although phages T7 and fd have previously been used as carriers to present M2e, they conferred limited protection ( 34 , 39 ). This is probably because these platforms cannot present full-length M2e peptides at high density, which is a key determinant for inducing strong and protective immune responses ( 52 ). Our data demonstrated that each T4 phage nanoparticle was decorated with ~427 copies of the 21.8 kDa Soc-3M2e, and each copy containing three tandem repeats of M2e peptide from human, swine, and avian influenza viruses.…”

Section: Discussionmentioning

confidence: 99%

Bacteriophage T4 Vaccine Platform for Next-Generation Influenza Vaccine Development

Guo

Chen

et al. 2021

Front. Immunol.

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Developing influenza vaccines that protect against a broad range of viruses is a global health priority. Several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is sufficiently immunogenic to elicit complete protection, and vaccine platforms that can enhance immunogenicity and deliver multiple antigens are desperately needed. Here, we report proof-of-concept studies for the development of next-generation influenza vaccines using the bacteriophage T4 virus-like particle (VLP) platform. Using the extracellular domain of influenza matrix protein 2 (M2e) as a readout, we demonstrate that up to ~1,281 M2e molecules can be assembled on a 120 x 86 nanometer phage capsid to generate M2e-T4 VLPs. These M2e-decorated nanoparticles, without any adjuvant, are highly immunogenic, stimulate robust humoral as well as cellular immune responses, and conferred complete protection against lethal influenza virus challenge. Potentially, additional conserved antigens could be incorporated into the M2e-T4 VLPs and mass-produced in E. coli in a short amount of time to deal with an emerging influenza pandemic.

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“…Since then, many groups have tried to target this region with mixed success. While some groups demonstrated broad cross-protection others found only modest protection levels to the homologous viral strain [24,[37][38][39][40]. However, to our knowledge, a single vaccine platform which simultaneously targets both HA-stalk and M2 protein antigens has not previously been produced or tested.…”

Section: Discussionmentioning

confidence: 99%

A virus-like particle vaccine candidate for influenza A virus based on multiple conserved antigens presented on hepatitis B tandem core particles

Ramirez

Morris

Maucourant

et al. 2018

Vaccine

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Existing Influenza A virus (IAV) vaccines target variable parts of the virus that may change between seasons. Vaccine design relies on predicting the predominant circulating influenza strains but when there is a mismatch between vaccine and circulating strains, efficacy is sub-optimal. Furthermore, current approaches provide limited protection against emerging influenza strains that may cause pandemics. One solution is to design vaccines that target conserved protein domains of influenza, which remain largely unchanged over time and are likely to be found in emergent variants. We present a virus-like particle (VLP), built using the hepatitis B virus tandem core platform, as an IAV vaccine candidate containing multiple conserved antigens. Hepatitis B core protein spontaneously assembles into a VLP that is immunogenic and confers immunogenicity to proteins incorporated into the major insertion region (MIR) of core monomers. However, insertion of antigen sequences may disrupt particle assembly preventing VLP formation or result in unstable particles. We have overcome these problems by genetically manipulating the hepatitis B core to express core monomers in tandem, ligated with a flexible linker, incorporating different antigens at each of the MIRs. Immunisation with this VLP, named Tandiflu1, containing 4 conserved antigens from matrix protein 2 ectodomain and hemagglutinin stalk, leads to production of cross-reactive and protective antibodies. The polyclonal antibodies induced by Tandiflu1 can bind IAV Group 1 hemagglutinin types H1, H5, H11, H9, H16 and a conserved epitope on matrix protein 2 expressed by most strains of IAV. Vaccination with Tandiflu1 results in 100% protection from a lethal influenza challenge with H1N1 IAV. Serum transfer from vaccinated animals is sufficient to confer protection from influenza-associated illness in naïve mice. These data suggest that a Tandem Core based IAV vaccine might provide broad protection against common and emergent H1 IAV strains responsible for seasonal and pandemic influenza in man.

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High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity

Cited by 8 publications

References 27 publications

Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

Bacteriophage T4 Vaccine Platform for Next-generation Influenza Vaccine Development

Bacteriophage T4 Vaccine Platform for Next-Generation Influenza Vaccine Development

A virus-like particle vaccine candidate for influenza A virus based on multiple conserved antigens presented on hepatitis B tandem core particles

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