Other
13 Authors
- Gravel C,
- Hashem AM,
- Jaentschke B,
- Li C,
- Wang J,
- He R,
- Li X,
- Yi Y,
- Fan X,
- Rosu-Myles M,
- Pereboev A,
- Chen Z,
- Tocchi M
| First Author | Hashem AM | Year | 2014 |
| Journal | J Immunol | Volume | 193 |
| Issue | 2 | Pages | 722-34 |
| PubMed ID | 24928989 | Mgi Jnum | J:337589 |
| Mgi Id | MGI:6839403 | Doi | 10.4049/jimmunol.1300093 |
| Citation | Hashem AM, et al. (2014) CD40 ligand preferentially modulates immune response and enhances protection against influenza virus. J Immunol 193(2):722-34 |
| abstractText | 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. |
