Recombinant H7 hemagglutinin expressed in glycoengineered Pichia pastoris forms nanoparticles that protect mice from challenge with H7N9 influenza virus

Liu, Bo; Shi, Ping‐Ping; Wang, Tiantian; Zhao, Yongkun; Lu, Shihao; Li, Xiang; Luo, Shiqiang; Chang, Shaohong; Wang, Sha; Sun, Peng; Gong, Xin; Gao, Yuwei; Wu, Jun

doi:10.1016/j.vaccine.2020.10.061

Cited by 10 publications

(15 citation statements)

References 63 publications

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“…Studies have shown that hyper-mannosylation modifications may mask the epitope of antigens [22] . The H7N9 influenza virus hemagglutinin (HA) subunit particle vaccine prepared by means of glycosylation-modified humanized yeast, which has mammalian N -glycosylation ability, has been shown to have good immunogenicity and protected mice from the H7N9 virus [11] . In this study, we used glycoengineered Pichia pastoris to express SARS-CoV-2 RBD.…”

Section: Discussionmentioning

confidence: 99%

“…The glycoengineered Pichia pastoris was reconstructed according to a previously reported method [16] , which has also been described in our previous work [11] . The bacterial strain was cultured in Luria–Bertani (LB) medium containing 1.5% agar.…”

Section: Methodsmentioning

confidence: 99%

“…Glycosylation engineering has led to the production of glycoengineered Pichia pastoris yeast, which performs glycosylation similar to that of mammalian cells while retaining the advantages of fast growth, low cost, and rapid reaction [9] , [10] . The H7N9 hemagglutinin glycoprotein vaccine expressed by glycoengineered yeast has been shown to have good immunogenicity and protective effects [11] .…”

Section: Introductionmentioning

confidence: 99%

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A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses

Liu¹,

Yin²,

Liu

et al. 2022

Engineering

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In 2020 and 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, caused a global pandemic. Vaccines are expected to reduce the pressure of prevention and control, and have become the most effective strategy to solve the pandemic crisis. SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2 (ACE2) via the receptor-binding domain (RBD) of the surface spike (S) glycoprotein. In this study, a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells. The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody. Furthermore, the specific antibody titer and virus-neutralizing antibody (NAb) titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH) 3 and CpG. Our results showed that the virus-NAb lasted for more than 6 months in mice. To summarize, we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris , which stimulates neutralizing and protective antibody responses. A technical route for fucose-free complex-type N -glycosylation modified recombinant subunit vaccine preparation has been established.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses

Liu¹,

Yin²,

Liu

et al. 2022

Engineering

Self Cite

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show abstract

“…HA and NA proteins are the major surface glycoproteins of influenza viruses. Reports have shown that the recombinant H7 HA subunit vaccine protects mice from H7N9 influenza virus challenge ( 16 , 17 ). NA expressing VLPs induced effective crossprotective immunity against influenza virus ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

“…Current influenza vaccine immunization only induces specific immune responses against strain-matched influenza viruses. This cannot provide effective protection when the circulating viruses generate antigenic drift or a new pandemic virus emerges ( 4 , 16 , 17 ). Therefore, developing an appropriate vaccination strategy is a high priority to improve the crossprotection of influenza vaccines and prevent future pandemic outbreaks.…”

Section: Introductionmentioning

confidence: 99%

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

Kong

Chen

et al. 2022

Front. Immunol.

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The continuous evolution of the H7N9 avian influenza virus suggests a potential outbreak of an H7N9 pandemic. Therefore, to prevent a potential epidemic of the H7N9 influenza virus, it is necessary to develop an effective crossprotective influenza vaccine. In this study, we developed H7N9 virus-like particles (VLPs) containing HA, NA, and M1 proteins derived from H7N9/16876 virus and a helper antigen HMN based on influenza conserved epitopes using a baculovirus expression vector system (BEVS). The results showed that the influenza VLP vaccine induced a strong HI antibody response and provided effective protection comparable with the effects of commercial inactivated H7N9 vaccines against homologous H7N9 virus challenge in chickens. Meanwhile, the H7N9 VLP vaccine induced robust crossreactive HI and neutralizing antibody titers against antigenically divergent H7N9 viruses isolated in wave 5 and conferred on chickens complete clinical protection against heterologous H7N9 virus challenge, significantly inhibiting virus shedding in chickens. Importantly, supplemented vaccination with HMN antigen can enhance Th1 immune responses; virus shedding was completely abolished in the vaccinated chickens. Our study also demonstrated that viral receptor-binding avidity should be taken into consideration in evaluating an H7N9 candidate vaccine. These studies suggested that supplementing influenza VLP vaccine with recombinant epitope antigen will be a promising strategy for the development of broad-spectrum influenza vaccines.

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The regulatory roles of Fasciola hepatica GSTO1 protein in inflammatory cytokine expression and apoptosis in murine macrophages

Xifeng,

Jiahua,

Ningxing

et al. 2023

Acta Tropica

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Recombinant H7 hemagglutinin expressed in glycoengineered Pichia pastoris forms nanoparticles that protect mice from challenge with H7N9 influenza virus

Cited by 10 publications

References 63 publications

A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses

A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses

Supplementation of H7N9 Virus-Like Particle Vaccine With Recombinant Epitope Antigen Confers Full Protection Against Antigenically Divergent H7N9 Virus in Chickens

The regulatory roles of Fasciola hepatica GSTO1 protein in inflammatory cytokine expression and apoptosis in murine macrophages

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