tetano
Editor, Senior Moderator
Accepted manuscript posted online 6 May 2015, doi: 10.1128/JVI.00549-15 JVI.00549-15
[h=1]Inclusion of flagellin during vaccination against influenza enhances recall responses in nonhuman primate neonates[/h]
[h=2]ABSTRACT[/h] Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a toll like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at risk population. Four to six day old AGM were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild type or mutant flagellin (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following boost, as well as at early times after challenge in infants vaccinated with flagellin adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza-specific T cells following challenge compared to infants vaccinated with m229 adjuvant. Finally, infants vaccinated with IPR8+flagellin exhibited reduced pathology in the lungs following challenge compared to those that received IPR8+m229. This study provides the first evidence of flagellin mediated enhancement of vaccine responses in nonhuman primate neonates.
Importance: Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.
http://jvi.asm.org/content/early/2015/04/30/JVI.00549-15.abstract
[h=1]Inclusion of flagellin during vaccination against influenza enhances recall responses in nonhuman primate neonates[/h]
- Jong R. Kim#,a,
- Beth C. Holbrooka,
- Sarah L. Haywarda,
- Lance K. Blevinsa,
- Matthew J. Jorgensenb,
- Nancy D. Kockb,
- Kristina De Parise,
- Ralph D'Agostino Jrc,
- S. Tyler Aycockd,
- Steven B. Mizela,
- Griffith D. Parksa and
- Martha A. Alexander-Millera#
- Department of Microbiology and Immunology[SUP]a[/SUP]
- Department of Pathology, Section of Comparative Medicine[SUP]b[/SUP]
- Department of Biostatistical Sciences[SUP]c[/SUP]
- Animal Resources Program[SUP]d[/SUP]
- Wake Forest School of Medicine, Winston-Salem, NC and University of North Carolina School of Medicine, Chapel Hill, NC[SUP]e[/SUP]
[h=2]ABSTRACT[/h] Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a toll like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at risk population. Four to six day old AGM were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild type or mutant flagellin (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following boost, as well as at early times after challenge in infants vaccinated with flagellin adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza-specific T cells following challenge compared to infants vaccinated with m229 adjuvant. Finally, infants vaccinated with IPR8+flagellin exhibited reduced pathology in the lungs following challenge compared to those that received IPR8+m229. This study provides the first evidence of flagellin mediated enhancement of vaccine responses in nonhuman primate neonates.
Importance: Young infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.
http://jvi.asm.org/content/early/2015/04/30/JVI.00549-15.abstract