CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Long, Yiru; Sun, Jianhua; Song, Tian-Zhang; Liu, Tingting; Tang, Feng; Zhang, Xinxin; Ding, Longfei; Miao, Yulong; Zhu, Weiliang; Pan, Xiaoyan; An, Q.; Qin, Mian; Tong, Xiaowei; Peng, Xionghua; Pan, Yu; Zhu, Peng; Xu, Jianqing; Zhang, Xiaoyan; Zhang, Yachun; Liu, Datao; Chen, Ben; Chen, Huilin; Zhang, Leike; Xiao, Gengfu; Zuo, Jian‐Ping; Tang, Wei; Zhou, Ji; Li, Heng; Xu, Zhijian; Zheng, Hong-Yi; Long, Xin-Yan; Qin, Qiuping; Gan, Yong; Ren, Jin; Huang, Wei; Zheng, Yong‐Tang; Jin, Guangyi; Gong, Likun

doi:10.1038/s41421-021-00370-2

Cited by 16 publications

(14 citation statements)

References 57 publications

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“…This epitope has also been used in other epitope-based vaccines, which showed humoral immune responses against Alpha, Beta, and Delta. 24 Therefore, the highly conserved IDf (450−469) epitope should be utilized to develop the nextgeneration pan-coronavirus vaccine rather than the infectivityenhancing IDg (480−499) epitope. In the research on antibody escape, it was reported that the fragment IDf (450−469) contains two escape sites with higher escape possibility, L455 and F456.…”

Section: ■ Discussionmentioning

confidence: 99%

“…The IDf (450–469) epitope showed high cross-reactivity against SARS-CoV-1 and SARS-CoV-2 and cross-neutralizing activity against the ancestral SARS-CoV-2, Delta, and Omicron (Figure F). This epitope has also been used in other epitope-based vaccines, which showed humoral immune responses against Alpha, Beta, and Delta . Therefore, the highly conserved IDf (450–469) epitope should be utilized to develop the next-generation pan-coronavirus vaccine rather than the infectivity-enhancing IDg (480–499) epitope.…”

Section: Discussionmentioning

confidence: 99%

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Non-Neutralizing Epitopes Shade Neutralizing Epitopes against Omicron in a Multiple Epitope-Based Vaccine

Gong

et al. 2022

ACS Infect. Dis.

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The ongoing coronavirus disease 2019 pandemic has raised concerns about the risk of re-infection. Non-neutralizing epitopes are one of the major reasons for antibody-dependent enhancement. Past studies on the ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have revealed an infectivity-enhancing site on the ancestral SARS-CoV-2 spike protein. However, infection enhancement associated with the SARS-CoV-2 Omicron strain remains elusive. In this study, we examined the antibodies induced by a multiple epitope-based vaccine, which showed infection enhancement for the Omicron strain but not for the ancestral SARS-CoV-2 or Delta strain. By examining the antibodies induced by single epitope-based vaccines, we identified a conserved epitope, IDf (450−469), with neutralizing activity against ancestral SARS-CoV-2, Delta, and Omicron. Although neutralizing epitopes are present in the multiple epitope-based vaccine, other immunodominant non-neutralizing epitopes such as IDg (480−499) can shade their neutralizing activity, leading to infection enhancement of Omicron. Our study provides up-to-date epitope information on SARS-CoV-2 variants to help design better vaccines or antibody-based therapeutics against future variants.

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Section: ■ Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Non-Neutralizing Epitopes Shade Neutralizing Epitopes against Omicron in a Multiple Epitope-Based Vaccine

Gong

et al. 2022

ACS Infect. Dis.

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“…The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is prone to specific mutations that alter viral surface peptide epitopes, making the virus more susceptible to immune escape ( 223 ). Peptide-based tumor vaccine research has also contributed to the development of COVID-19 vaccines targeting COVID-19-specific peptide epitopes ( 224 , 225 ).…”

Section: Discussionmentioning

confidence: 99%

Potential association factors for developing effective peptide-based cancer vaccines

et al. 2022

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Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

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“…At the beginning of this pandemic, peptide-based vaccines have been unappreciated unfortunately ( Shalash et al, 2021 ). However, a new conjugated self-adjuvanting peptide vaccine with an immune agonist is a promising approach to improve immunogenicity as well as other peptide-based vaccination effects ( Long et al, 2022 ). Synthetic vaccines can be rapidly developed as a fast response against other pandemic-prone pathogens.…”

Section: Landscape Of Opportunities: Topical Insightsmentioning

confidence: 99%

Smart therapies against global pandemics: A potential of short peptides

et al. 2022

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BackgroundAs we entered the third year of this pandemic, since the World Health Organisation (WHO) declared in March 2020 the novel coronavirus severe acute respiratory syndrome (SARS-CoV2) outbreak as a global pandemic COVID-19 (COronaVIrus Disease 19), we are still fighting with newer and newer viral mutations. The pandemic has passed the grim milestone of over 6.4 million COVID19 deaths, from more than 550 million reported cases thus far. In fact, more than 15 million people can die by the end of this year. It is highly likely that this pandemic will become endemic, while the full evolutionary potential of coronaviruses has yet to be revealed. The next pandemic is coming. A microbe with features of SARS-Middle East respiratory syndrome (MERS) and SARS-CoV-2 could lead to significantly more catastrophic loss of life. The co-evolution with other viruses should not be neglected. According to the WHO, we should expect diverse zoonotic, outbreakprone microbes, including highly pathogenic strains of influenza, Nipah, Ebola, Zika, or hemorrhagic fever viruses. 'It's an evolutionary certainty that there will be another virus with the potential to be more transmittable and deadly than this one', said Tedros Adhanom Ghebreyesus, director-general of the WHO. On the other hand, in both poor countries and regions of armed conflict, where vaccination is hampered, historic diseases are re-emerging, with migration and displacement influencing transmission risk and limiting control, and raising potential for additional outbreaks. Furthermore, there are other looming terrible threats to humanity as damaging as the bubonic plagues, such as bioterrorism or antibiotic resistant microorganisms. In most cases, both effective prevention and treatment options are limited.

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CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity

Cited by 16 publications

References 57 publications

Non-Neutralizing Epitopes Shade Neutralizing Epitopes against Omicron in a Multiple Epitope-Based Vaccine

Non-Neutralizing Epitopes Shade Neutralizing Epitopes against Omicron in a Multiple Epitope-Based Vaccine

Potential association factors for developing effective peptide-based cancer vaccines

Smart therapies against global pandemics: A potential of short peptides

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