tetano
Editor, Senior Moderator
J Immunol. 2014 Jun 13. pii: 1300093. [Epub ahead of print]
CD40 Ligand Preferentially Modulates Immune Response and Enhances Protection against Influenza Virus.
Hashem AM1, Gravel C2, Chen Z3, Yi Y3, Tocchi M2, Jaentschke B2, Fan X4, Li C4, Rosu-Myles M2, Pereboev A5, He R6, Wang J7, Li X8.
Author information
Abstract
CD40L, a key regulator of the immune system, was studied as both a targeting ligand and a molecular adjuvant in nucleoprotein (NP)-based host defense against influenza in mouse models with different genetic backgrounds. Adenoviral vectors secreting NP-CD40L fusion protein (denoted as rAd-SNP40L) afforded full protection of immunocompetent and immunocompromised mice (CD40L-/- and CD4-/-) against lethal influenza infection. Mechanistically, rAd-SNP40L preferentially induced early and persistent B cell germinal center formation, and accelerated Ig isotype-switching and Th1-skewed, NP-specific Ab response. Moreover, it drastically augmented primary and memory NP-specific CTL activity and polyfunctional CD8+ T cells. The markedly enhanced nonneutralizing Abs and CTLs significantly reduced viral burdens in the lungs of mice upon lethal virus challenge. Data generated from CD40L-/- and CD4-/- mice revealed that the protection was indeed CD40L mediated but CD4+ T cell independent, demonstrating the viability of the fusion Ags in protecting immunodeficient hosts. Notably, a single dose of rAd-SNP40L completely protected mice from lethal viral challenge 4 mo after immunization, representing the first report, to our knowledge, on NP in conjunction with a molecular adjuvant inducing a robust and long-lasting memory immune response against influenza. This platform is characterized by an increased in vivo load of CD40-targeted Ag upon the secretion of the fusion protein from adenovirus-infected cells and may represent a promising strategy to enhance the breadth, durability, and potency of Ag-specific immune responses.
Copyright ? 2014 by The American Association of Immunologists, Inc.
PMID:
24928989
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24928989
CD40 Ligand Preferentially Modulates Immune Response and Enhances Protection against Influenza Virus.
Hashem AM1, Gravel C2, Chen Z3, Yi Y3, Tocchi M2, Jaentschke B2, Fan X4, Li C4, Rosu-Myles M2, Pereboev A5, He R6, Wang J7, Li X8.
Author information
Abstract
CD40L, a key regulator of the immune system, was studied as both a targeting ligand and a molecular adjuvant in nucleoprotein (NP)-based host defense against influenza in mouse models with different genetic backgrounds. Adenoviral vectors secreting NP-CD40L fusion protein (denoted as rAd-SNP40L) afforded full protection of immunocompetent and immunocompromised mice (CD40L-/- and CD4-/-) against lethal influenza infection. Mechanistically, rAd-SNP40L preferentially induced early and persistent B cell germinal center formation, and accelerated Ig isotype-switching and Th1-skewed, NP-specific Ab response. Moreover, it drastically augmented primary and memory NP-specific CTL activity and polyfunctional CD8+ T cells. The markedly enhanced nonneutralizing Abs and CTLs significantly reduced viral burdens in the lungs of mice upon lethal virus challenge. Data generated from CD40L-/- and CD4-/- mice revealed that the protection was indeed CD40L mediated but CD4+ T cell independent, demonstrating the viability of the fusion Ags in protecting immunodeficient hosts. Notably, a single dose of rAd-SNP40L completely protected mice from lethal viral challenge 4 mo after immunization, representing the first report, to our knowledge, on NP in conjunction with a molecular adjuvant inducing a robust and long-lasting memory immune response against influenza. This platform is characterized by an increased in vivo load of CD40-targeted Ag upon the secretion of the fusion protein from adenovirus-infected cells and may represent a promising strategy to enhance the breadth, durability, and potency of Ag-specific immune responses.
Copyright ? 2014 by The American Association of Immunologists, Inc.
PMID:
24928989
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24928989