HASHEM AM, Gravel C, Chen Z, Yi Y, et al. CD40 Ligand Preferentially Modulates Immune Response and Enhances Protection against Influenza Virus. J Immunol. 2014 Jun 13. pii: 1300093.
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.
See Also:
Latest articles in those days:
- [preprint] Potential Pathways of Spread of Highly Pathogenic Avian Influenza A/H5N1 Clade 2.3.4.4b Across Dairy Farms in the United States 5 hours ago
- [preprint] The avian and human influenza A virus receptors sialic acid (SA)-α2,3 and SA-α2,6 are widely expressed in the bovine mammary gland 6 hours ago
- Repeatability and reproducibility of hunter-harvest sampling for avian influenza virus surveillance in Great Britain 6 hours ago
- The RBPome of influenza A virus NP-mRNA reveals a role for TDP-43 in viral replication 6 hours ago
- Novel Genotype of HA Clade 2.3.4.4b H5N8 Subtype High Pathogenicity Avian Influenza Virus Emerged at a Wintering Site of Migratory Birds in Japan, 2021/22 Winter 6 hours ago
[Go Top] [Close Window]