tetano
Editor, Senior Moderator
Front Immunol. 2017 Dec 8;8:1730. doi: 10.3389/fimmu.2017.01730. eCollection 2017.
[h=1]Cross-Protective Efficacy of Influenza Virus M2e Containing Virus-Like Particles Is Superior to Hemagglutinin Vaccines and Variable Depending on the Genetic Backgrounds of Mice.[/h] Kim YJ[SUP]1[/SUP], Lee YT[SUP]1[/SUP], Kim MC[SUP]1,[/SUP][SUP]2[/SUP], Lee YN[SUP]1,[/SUP][SUP]2[/SUP], Kim KH[SUP]1[/SUP], Ko EJ[SUP]1[/SUP], Song JM[SUP]3[/SUP], Kang SM[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus M2 extracellular domain (M2e) has been a target for developing cross-protective vaccines. However, the efficacy and immune correlates of M2e vaccination are poorly understood in the different host genetic backgrounds in comparison with influenza vaccines. We previously reported the cross-protective efficacy of virus-like particle (M2e5x VLP) vaccines containing heterologous tandem M2e repeats (M2e5x) derived from human, swine, and avian influenza viruses. In this study to gain better understanding of cross-protective influenza vaccines, we compared immunogenicity and efficacy of M2e5x VLP, H5 hemagglutinin VLP (HA VLP), and inactivated H3N2 virus (H3N2i) in wild-type strains of BALB/c and C57BL/6 mice, and CD4 and CD8 knockout (KO) mice. M2e5x VLP was superior to HA VLP in conferring cross-protection whereas H3N2i inactivated virus vaccine provided high efficacy of homologous protection. After M2e5x VLP vaccination and challenge, BALB/c mice induced higher IgG responses, lower lung viral loads, and less body weight loss when compared with those in C57BL/6 mice. M2e5x VLP but not H3N2i immune mice after primary challenges developed strong immunity against a secondary heterosubtypic virus as a model of future pandemics. M2e5x VLP and HA VLP vaccines were able to raise IgG isotypes in CD4 KO mice. T cells were found to contribute to cross-protection by playing a role in reducing lung viral loads. In conclusion, M2e5x VLP vaccination induced better cross-protection than HA VLP, and its efficacy varied depending on the genetic backgrounds of mice, supporting the important roles of T cells.
[h=4]KEYWORDS:[/h] BALB/C; C57BL/6; CD4 and CD8 T cells; M2e virus-like particles; influenza virus
PMID: 29276514 PMCID: PMC5727122 DOI: 10.3389/fimmu.2017.01730
[h=1]Cross-Protective Efficacy of Influenza Virus M2e Containing Virus-Like Particles Is Superior to Hemagglutinin Vaccines and Variable Depending on the Genetic Backgrounds of Mice.[/h] Kim YJ[SUP]1[/SUP], Lee YT[SUP]1[/SUP], Kim MC[SUP]1,[/SUP][SUP]2[/SUP], Lee YN[SUP]1,[/SUP][SUP]2[/SUP], Kim KH[SUP]1[/SUP], Ko EJ[SUP]1[/SUP], Song JM[SUP]3[/SUP], Kang SM[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Influenza virus M2 extracellular domain (M2e) has been a target for developing cross-protective vaccines. However, the efficacy and immune correlates of M2e vaccination are poorly understood in the different host genetic backgrounds in comparison with influenza vaccines. We previously reported the cross-protective efficacy of virus-like particle (M2e5x VLP) vaccines containing heterologous tandem M2e repeats (M2e5x) derived from human, swine, and avian influenza viruses. In this study to gain better understanding of cross-protective influenza vaccines, we compared immunogenicity and efficacy of M2e5x VLP, H5 hemagglutinin VLP (HA VLP), and inactivated H3N2 virus (H3N2i) in wild-type strains of BALB/c and C57BL/6 mice, and CD4 and CD8 knockout (KO) mice. M2e5x VLP was superior to HA VLP in conferring cross-protection whereas H3N2i inactivated virus vaccine provided high efficacy of homologous protection. After M2e5x VLP vaccination and challenge, BALB/c mice induced higher IgG responses, lower lung viral loads, and less body weight loss when compared with those in C57BL/6 mice. M2e5x VLP but not H3N2i immune mice after primary challenges developed strong immunity against a secondary heterosubtypic virus as a model of future pandemics. M2e5x VLP and HA VLP vaccines were able to raise IgG isotypes in CD4 KO mice. T cells were found to contribute to cross-protection by playing a role in reducing lung viral loads. In conclusion, M2e5x VLP vaccination induced better cross-protection than HA VLP, and its efficacy varied depending on the genetic backgrounds of mice, supporting the important roles of T cells.
[h=4]KEYWORDS:[/h] BALB/C; C57BL/6; CD4 and CD8 T cells; M2e virus-like particles; influenza virus
PMID: 29276514 PMCID: PMC5727122 DOI: 10.3389/fimmu.2017.01730