Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles

Wang, Daning; Liu, Xinlin; Wei, Minxi; Qian, Ciying; Song, Shuo; Chen, Jie; Wang, Zhiping; Xu, Qiang; Yang, Yurou; He, Maozhou; Chi, Xiaosa; Huang, Shunlin; Li, Tingting; Kong, Zhibo; Zheng, Qingbing; Yu, Hai; Wang, Yingbin; Zhao, Qinjian; Zhang, Jun; Xia, Ningshao; Gu, Ying; Li, Shaowei

doi:10.1038/s41467-020-16639-1

Cited by 27 publications

(15 citation statements)

References 64 publications

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“…Due to the lack of protein glycosylation and the formation of inclusion bodies in prokaryotic expression systems, most vaccine development efforts targeting SARS-CoV-2 have focused on mammalian expression systems instead of the highly efficient E. coli system. 5 , 36 However, studies have reported successful development of antiviral vaccines with the use of E. coli for expression, such as the expression of virus-like particle (VLP) structures of human papillomavirus (HPV) and hepatitis E virus (HEV) 37 , 38 and the use of OMVs to deliver viral antigens of dengue virus, influenza virus, and Middle East respiratory syndrome (MERS) coronavirus. 11 , 39 , 40 Therefore, when using an E. coli expression system, vaccines should form stable polymers and regular nanostructures, and RBD-BBVs designed by us meet those requirements.…”

Section: Results and Discussionmentioning

confidence: 99%

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2

et al. 2021

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The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a “ring-like” bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.

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Section: Results and Discussionmentioning

confidence: 99%

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2

et al. 2021

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“…E. coli is the most productive and least costly protein expression system. Vaccines against SARS [ 35 ], dengue fever [ 29 ], Middle East respiratory syndrome [ 36 ], hepatitis E [ 37 ], influenza [ 38 ], and human papillomavirus [ 39 ] have been successfully expressed as nanostructures in E. coli . Therefore, the correct folding or assembly of viral antigens into nanostructures in E. coli could elicit potential immune protection, thus enabling the successful development of an inexpensive vaccine in E. coli .…”

Section: Discussionmentioning

confidence: 99%

Polymerized porin as a novel delivery platform for coronavirus vaccine

et al. 2022

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Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), seriously threatens human life and health. The correct folding and polymerization of the receptor-binding domain (RBD) protein of coronavirus in Escherichia coli may reduce the cost of SARS-CoV-2 vaccines. In this study, we constructed this nanopore by using the principle of ClyA porin polymerization triggered by the cell membrane. We used surfactants to "pick" the ClyA-RBD nanopore from the bacterial outer membrane. More importantly, the polymerized RBD displayed on the ClyA-RBD polymerized porin (RBD-PP) already displays some correct spatial conformational epitopes that can induce neutralizing antibodies. The nanostructures of RBD-PP can target lymph nodes and promote antigen uptake and processing by dendritic cells, thereby effectively eliciting the production of anti-SARS-CoV-2 neutralizing antibodies, systemic cellular immune responses, and memory T cells. We applied this PP-based vaccine platform to fabricate an RBD-based subunit vaccine against SARS-CoV-2, which will provide a foundation for the development of inexpensive coronavirus vaccines. The development of a novel vaccine delivery system is an important part of innovative drug research. This novel PP-based vaccine platform is likely to have additional applications, including other viral vaccines, bacterial vaccines, tumor vaccines, drug delivery, and disease diagnosis. Graphical Abstract

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“…Researchers are developing PCR tests to detect more HPV genotypes [31] and are proposing methods to produce vaccines that can prevent HPV of other genotypes. [48] Currently, some genotypes with the highest infection rates in Canada are not targeted by PCR tests or vaccines. We recommend a better alignment of the genotypes targeted by HPV tests and vaccines with those genotypes with the highest infection rates in Canada.…”

Section: Discussionmentioning

confidence: 99%

Human Papillomavirus Infection Rate by Genotype and Vaccination Rates in Canada: Canadian Health Measures Survey 2009 to 2013

Chao

2022

Preprint

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BackgroundAn infection with certain HPV genotypes can lead to cancer or genital warts. HPV can be detected with PCR-based tests, and some genotypes can be prevented by vaccines. However, since the infection rates of various HPV genotypes have not been well reported, the present study aims to provide this information.MethodsThe Canadian Health Measures Survey (CHMS) is an ongoing biannual national survey. Between 2009 and 2011, it sampled a nationally representative sample of females aged 14 to 59 years to determine the infection rates of 46 HPV genotypes. Females aged 9 to 29 years and 9 to 59 years were asked whether they received HPV vaccines between 2009 to 2011 (cycle 2) and 2012 to 2013 (cycle 3), respectively. The reported infection rates and vaccination proportions were weighted and adjusted for the survey design.ResultsAmong the estimated 10,592,968 females aged 14 to 59 years at cycle 2, the HPV genotypes with the highest infection rates were 16, 62, 74, and 54, and the rates were 3.42% (95% CI = 1.67% to 5.17%), 2.14% (95% CI = 0.68% to 3.59%), 2.1% (95% CI = 0.51% to 3.69%), and 2.04% (95% CI = 0.38% to 3.7%), respectively. There were an estimated 6,569,100 and 11,603,752 females aged 9 to 29 and 9 to 59 years at cycles 2 and 3, respectively. The proportions receiving a HPV vaccine were 13.55% (11.18% to 15.92%) and 12.3% (9.8% to 14.79%), respectively. The estimated numbers of females that received HPV vaccines were 890,197 and 1,427,000, respectively.ConclusionCanada is one of the few countries that conduct national surveys to determine HPV infection rates by genotype, which are not limited to the surveillance of carcinogenic genotypes. Our study found discrepancies between the HPV genotypes whose infections were the most common, that could be detected by PCR tests, that were carcinogenic, and that could be prevented by vaccines. For example, 5 of the 7 genotypes (42, 54, 62, 66, and 74) with infection rates of more than 1% cannot be detected by PCR tests and are not targeted by vaccines. HPV 51 is carcinogenic, associated with genital warts, and can be detected by PCR tests, but it is not targeted by vaccines. We recommend a better alignment of the genotypes targeted by HPV tests and vaccines with those genotypes with the highest infection rates in Canada.

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Rational design of a multi-valent human papillomavirus vaccine by capsomere-hybrid co-assembly of virus-like particles

Cited by 27 publications

References 64 publications

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2

Polymerized porin as a novel delivery platform for coronavirus vaccine

Human Papillomavirus Infection Rate by Genotype and Vaccination Rates in Canada: Canadian Health Measures Survey 2009 to 2013

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