tetano
Editor, Senior Moderator
Mol Ther Methods Clin Dev
. 2022 May 29;26:38-51.
doi: 10.1016/j.omtm.2022.05.007. eCollection 2022 Sep 8.
Thermostable H1 hemagglutinin stem with M2e epitopes provides broad cross-protection against group1 and 2 influenza A viruses
Jeeva Subbbiah[SUP] 1 [/SUP], Judy Oh[SUP] 1 [/SUP], Ki-Hye Kim[SUP] 1 [/SUP], Chong Hyun Shin[SUP] 1 [/SUP], Bo Ryoung Park[SUP] 1 [/SUP], Noopur Bhatnagar[SUP] 1 [/SUP], Yu-Jin Jung[SUP] 1 [/SUP], Youri Lee[SUP] 1 [/SUP], Bao-Zhong Wang[SUP] 1 [/SUP], Baik-Lin Seong[SUP] 2 3 [/SUP], Sang-Moo Kang[SUP] 1 [/SUP]
Affiliations
Abstract
Hemagglutinin (HA) stem-based vaccines have limitations in providing broad and effective protection against cross-group influenza viruses, despite being a promising universal vaccine target. To overcome the limited cross-protection and low efficacy by HA stem vaccination, we genetically engineered a chimeric conjugate of thermostable H1 HA stem and highly conserved M2e repeat (M2e-H1stem), which was expressed at high yields in Escherichia coli. M2e-H1stem protein presented native-like epitopes reactive to antisera of live virus infection. M2e-H1stem protein vaccination of mice induced strong M2e- and HA stem-specific immune responses, conferring broadly effective cross-protection against both antigenically distinct group 1 (H1N1, H5N1, and H9N2 subtypes) and group 2 (H3N2 and H7N9 subtypes) seasonal and pandemic potential influenza viruses. M2e-H1stem vaccination generated CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses and antibody-dependent cytotoxic cellular and humoral immunity, which contributed to enhancing cross-protection. Furthermore, comparable broad cross-group protection was observed in older aged mice after M2e-H1stem vaccination. This study provides evidence warranting further development of chimeric M2e-stem proteins as a promising universal influenza vaccine candidate in adult and aged populations.
Keywords: M2e; chimeric M2e-H1stem protein; cross-group protection; influenza A virus.
. 2022 May 29;26:38-51.
doi: 10.1016/j.omtm.2022.05.007. eCollection 2022 Sep 8.
Thermostable H1 hemagglutinin stem with M2e epitopes provides broad cross-protection against group1 and 2 influenza A viruses
Jeeva Subbbiah[SUP] 1 [/SUP], Judy Oh[SUP] 1 [/SUP], Ki-Hye Kim[SUP] 1 [/SUP], Chong Hyun Shin[SUP] 1 [/SUP], Bo Ryoung Park[SUP] 1 [/SUP], Noopur Bhatnagar[SUP] 1 [/SUP], Yu-Jin Jung[SUP] 1 [/SUP], Youri Lee[SUP] 1 [/SUP], Bao-Zhong Wang[SUP] 1 [/SUP], Baik-Lin Seong[SUP] 2 3 [/SUP], Sang-Moo Kang[SUP] 1 [/SUP]
Affiliations
- PMID: 35755946
- PMCID: PMC9198381
- DOI: 10.1016/j.omtm.2022.05.007
Abstract
Hemagglutinin (HA) stem-based vaccines have limitations in providing broad and effective protection against cross-group influenza viruses, despite being a promising universal vaccine target. To overcome the limited cross-protection and low efficacy by HA stem vaccination, we genetically engineered a chimeric conjugate of thermostable H1 HA stem and highly conserved M2e repeat (M2e-H1stem), which was expressed at high yields in Escherichia coli. M2e-H1stem protein presented native-like epitopes reactive to antisera of live virus infection. M2e-H1stem protein vaccination of mice induced strong M2e- and HA stem-specific immune responses, conferring broadly effective cross-protection against both antigenically distinct group 1 (H1N1, H5N1, and H9N2 subtypes) and group 2 (H3N2 and H7N9 subtypes) seasonal and pandemic potential influenza viruses. M2e-H1stem vaccination generated CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses and antibody-dependent cytotoxic cellular and humoral immunity, which contributed to enhancing cross-protection. Furthermore, comparable broad cross-group protection was observed in older aged mice after M2e-H1stem vaccination. This study provides evidence warranting further development of chimeric M2e-stem proteins as a promising universal influenza vaccine candidate in adult and aged populations.
Keywords: M2e; chimeric M2e-H1stem protein; cross-group protection; influenza A virus.