tetano
Editor, Senior Moderator
Vaccine
. 2020 Jul 23;S0264-410X(20)30915-4.
doi: 10.1016/j.vaccine.2020.07.015. Online ahead of print.
A biomimetic VLP influenza vaccine with interior NP/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy
Jiangxue Wei[SUP] 1 [/SUP], Zhengjun Li[SUP] 2 [/SUP], Yanli Yang[SUP] 2 [/SUP], Xiaowei Ma[SUP] 3 [/SUP], Wenqi An[SUP] 3 [/SUP], Guanghui Ma[SUP] 2 [/SUP], Zhiguo Su[SUP] 4 [/SUP], Songping Zhang[SUP] 5 [/SUP]
Affiliations
Abstract
Here we present a biomimetic strategy towards an influenza vaccine design based on hepatitis B virus core virus-like particles (HBc VLP). To this end, a temperature-shift based encapsulation process based on analysis of the unique thermal-associated structural flexibility of HBc VLP nanocages was proposed and proved efficient for encapsulation of antigen inside the VLP. By displaying a matrix protein 2 ectodomain (M2e) antigen on the exterior of HBc VLP through genetic fusion, and encapsulate a conserved internal nucleoprotein (NP) antigen peptide inside the VLP, a biomimetic dual-antigen influenza vaccine with interior NP/exterior M2e was constructed. For comparison, another non-biomimetic dual-antigen vaccine with interior M2e/exterior NP, and other four VLP-based single-antigen vaccines with NP or M2e either being encapsulated inside or genetically displayed outside the VLP were also constructed. Upon intraperitoneal immunization in mice, the dual-antigen VLP influenza vaccine elicited both NP and M2e-specific antibodies, which were stronger than those elicited by the single-antigen vaccines. Most importantly, after a lethal challenge of H1N1 virus, the biomimetic dual-antigen vaccine conferred the mice 100% protection without noticeable body weight loss in the absence of any adjuvant. While the protective efficacy conferred by the non-biomimetic one was only 62.5%, accompanying 12.5% body weight loss in the immunized mice. Besides the high level of antigen-specific antibodies, more efficient formation of total germinal center (GC) B cells and a higher level of effector memory CD8[SUP]+[/SUP] T cell population were observed in the biomimetic vaccine group, as compared with the non-biomimetic one. All these results demonstrate that VLP assembly and display of antigens in a biomimetic manner making this a promising strategy for the production of efficient universal vaccines to influenza and other rapidly emerging pathogens.
Keywords: Biomimetic; Influenza vaccine; M2e; Nucleoprotein; Virus like-particles.
. 2020 Jul 23;S0264-410X(20)30915-4.
doi: 10.1016/j.vaccine.2020.07.015. Online ahead of print.
A biomimetic VLP influenza vaccine with interior NP/exterior M2e antigens constructed through a temperature shift-based encapsulation strategy
Jiangxue Wei[SUP] 1 [/SUP], Zhengjun Li[SUP] 2 [/SUP], Yanli Yang[SUP] 2 [/SUP], Xiaowei Ma[SUP] 3 [/SUP], Wenqi An[SUP] 3 [/SUP], Guanghui Ma[SUP] 2 [/SUP], Zhiguo Su[SUP] 4 [/SUP], Songping Zhang[SUP] 5 [/SUP]
Affiliations
- PMID: 32713681
- DOI: 10.1016/j.vaccine.2020.07.015
Abstract
Here we present a biomimetic strategy towards an influenza vaccine design based on hepatitis B virus core virus-like particles (HBc VLP). To this end, a temperature-shift based encapsulation process based on analysis of the unique thermal-associated structural flexibility of HBc VLP nanocages was proposed and proved efficient for encapsulation of antigen inside the VLP. By displaying a matrix protein 2 ectodomain (M2e) antigen on the exterior of HBc VLP through genetic fusion, and encapsulate a conserved internal nucleoprotein (NP) antigen peptide inside the VLP, a biomimetic dual-antigen influenza vaccine with interior NP/exterior M2e was constructed. For comparison, another non-biomimetic dual-antigen vaccine with interior M2e/exterior NP, and other four VLP-based single-antigen vaccines with NP or M2e either being encapsulated inside or genetically displayed outside the VLP were also constructed. Upon intraperitoneal immunization in mice, the dual-antigen VLP influenza vaccine elicited both NP and M2e-specific antibodies, which were stronger than those elicited by the single-antigen vaccines. Most importantly, after a lethal challenge of H1N1 virus, the biomimetic dual-antigen vaccine conferred the mice 100% protection without noticeable body weight loss in the absence of any adjuvant. While the protective efficacy conferred by the non-biomimetic one was only 62.5%, accompanying 12.5% body weight loss in the immunized mice. Besides the high level of antigen-specific antibodies, more efficient formation of total germinal center (GC) B cells and a higher level of effector memory CD8[SUP]+[/SUP] T cell population were observed in the biomimetic vaccine group, as compared with the non-biomimetic one. All these results demonstrate that VLP assembly and display of antigens in a biomimetic manner making this a promising strategy for the production of efficient universal vaccines to influenza and other rapidly emerging pathogens.
Keywords: Biomimetic; Influenza vaccine; M2e; Nucleoprotein; Virus like-particles.