tetano
Editor, Senior Moderator
Immun Ageing. 2019 Sep 2;16:23. doi: 10.1186/s12979-019-0162-y. eCollection 2019.
[h=1]AuNP-M2e + sCpG vaccination of juvenile mice generates lifelong protective immunity to influenza A virus infection.[/h] Bimler L[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Song AY[SUP]1,[/SUP][SUP]3[/SUP], Le DT[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Murphy Schafer A[SUP]1,[/SUP][SUP]5[/SUP], Paust S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h] 1 1Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital, Houston, TX 77030 USA. 2 2Graduate Program in Immunology, Baylor College of Medicine, Houston, TX 77030 USA. 3 3Developing Investigative Scholar's Program (DISP), Rice University, Houston, TX 77030 USA. 4 4Department of Immunology and Microbiology, The Scripps Research Institute, Immunology Building 313/114, 10466 North Torrey Pines Road, La Jolla, California, 92037 USA. 5 5Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030 USA.
[h=3]Abstract[/h] [h=4]Background:[/h] Influenza virus infection causes significant morbidity and mortality worldwide. Humans fail to make a universally protective memory response to influenza A because of high mutation rates in the immune-dominant influenza epitopes. We seek the development of a universal influenza A vaccine. The extracellular domain of the M2-ion channel (M2e) is an ideal antigenic target, as it is highly conserved, has a low mutation rate, and is essential for viral entry and replication. Considering the potential of a universal influenza vaccine for lifelong protection, we aimed to examine this potential using a recently published gold nanoparticle M2e vaccine with CpG as an adjuvant (AuNP-M2e + sCpG). Intranasal vaccination induces an M2e-specific memory response, which is protective against lethal infection with H1N1, H3N2, and H5N1 serotypes, in young BALB/c mice. Protection with AuNP-M2e + sCpG has been published up to 8 months after vaccination. However, the highest risk population during most influenza seasons is adults over 65 years old. Additionally, the efficacy of many vaccines decrease after aging and requiring booster vaccinations to remain effective.
[h=4]Results:[/h] To determine if the AuNP-M2e + sCpG vaccine is a viable option as a universal vaccination capable of protection through geriatric age, we tested if the AuNP-M2e + sCpG vaccination loses efficacy after aging mice to geriatric age (over 18 months). Our data shows that mice aged 15 months after vaccination (~ 18-21 months old) retain significant M2e-specific antibody titers in total IgG, IgG1, IgG2a, and IgG2b. These mice are significantly protected from lethal influenza challenge (H1N1, 8.3 PFU). Further, these antibody titers increase upon infection with influenza A and remain elevated for 3 months, suggesting the elderly mice retain effective M2e-specific memory B cells.
[h=4]Conclusions:[/h] Our results demonstrate that protective M2e-specific memory in mice developed at a young age can persist until geriatric age. Additionally, this memory is protective and M2e-specific B cells produced by vaccination with AuNP-M2e + sCpG are maintained and functional. If the results of this study persist in humans, they suggest that a universal influenza A vaccine could be administered early in life and maintain lifelong protection into geriatric age.
[h=4]KEYWORDS:[/h] Geriatric; Influenza a; M2e; Nanoparticle; Vaccine
PMID: 31507643 PMCID: PMC6720989 DOI: 10.1186/s12979-019-0162-y
Free PMC Article
[h=1]AuNP-M2e + sCpG vaccination of juvenile mice generates lifelong protective immunity to influenza A virus infection.[/h] Bimler L[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4[/SUP], Song AY[SUP]1,[/SUP][SUP]3[/SUP], Le DT[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Murphy Schafer A[SUP]1,[/SUP][SUP]5[/SUP], Paust S[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3,[/SUP][SUP]4,[/SUP][SUP]5[/SUP].
[h=3]Author information[/h] 1 1Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital, Houston, TX 77030 USA. 2 2Graduate Program in Immunology, Baylor College of Medicine, Houston, TX 77030 USA. 3 3Developing Investigative Scholar's Program (DISP), Rice University, Houston, TX 77030 USA. 4 4Department of Immunology and Microbiology, The Scripps Research Institute, Immunology Building 313/114, 10466 North Torrey Pines Road, La Jolla, California, 92037 USA. 5 5Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030 USA.
[h=3]Abstract[/h] [h=4]Background:[/h] Influenza virus infection causes significant morbidity and mortality worldwide. Humans fail to make a universally protective memory response to influenza A because of high mutation rates in the immune-dominant influenza epitopes. We seek the development of a universal influenza A vaccine. The extracellular domain of the M2-ion channel (M2e) is an ideal antigenic target, as it is highly conserved, has a low mutation rate, and is essential for viral entry and replication. Considering the potential of a universal influenza vaccine for lifelong protection, we aimed to examine this potential using a recently published gold nanoparticle M2e vaccine with CpG as an adjuvant (AuNP-M2e + sCpG). Intranasal vaccination induces an M2e-specific memory response, which is protective against lethal infection with H1N1, H3N2, and H5N1 serotypes, in young BALB/c mice. Protection with AuNP-M2e + sCpG has been published up to 8 months after vaccination. However, the highest risk population during most influenza seasons is adults over 65 years old. Additionally, the efficacy of many vaccines decrease after aging and requiring booster vaccinations to remain effective.
[h=4]Results:[/h] To determine if the AuNP-M2e + sCpG vaccine is a viable option as a universal vaccination capable of protection through geriatric age, we tested if the AuNP-M2e + sCpG vaccination loses efficacy after aging mice to geriatric age (over 18 months). Our data shows that mice aged 15 months after vaccination (~ 18-21 months old) retain significant M2e-specific antibody titers in total IgG, IgG1, IgG2a, and IgG2b. These mice are significantly protected from lethal influenza challenge (H1N1, 8.3 PFU). Further, these antibody titers increase upon infection with influenza A and remain elevated for 3 months, suggesting the elderly mice retain effective M2e-specific memory B cells.
[h=4]Conclusions:[/h] Our results demonstrate that protective M2e-specific memory in mice developed at a young age can persist until geriatric age. Additionally, this memory is protective and M2e-specific B cells produced by vaccination with AuNP-M2e + sCpG are maintained and functional. If the results of this study persist in humans, they suggest that a universal influenza A vaccine could be administered early in life and maintain lifelong protection into geriatric age.
[h=4]KEYWORDS:[/h] Geriatric; Influenza a; M2e; Nanoparticle; Vaccine
PMID: 31507643 PMCID: PMC6720989 DOI: 10.1186/s12979-019-0162-y
Free PMC Article