scholarly journals The impact of antigen expression in antigen-presenting cells on humoral immune responses against the transgene product

Gene Therapy ◽  
2009 ◽  
Vol 17 (2) ◽  
pp. 288-293 ◽  
Author(s):  
Y Feng ◽  
F Jacobs ◽  
E Van Craeyveld ◽  
J Lievens ◽  
J Snoeys ◽  
...  
2018 ◽  
Vol 9 ◽  
Author(s):  
Julien Cachat ◽  
Christine Deffert ◽  
Marco Alessandrini ◽  
Pascale Roux-Lombard ◽  
Audrey Le Gouellec ◽  
...  

2012 ◽  
Vol 23 (9) ◽  
pp. 943-950 ◽  
Author(s):  
Natalie A. Hutnick ◽  
Devin J.F. Myles ◽  
Bernadette Ferraro ◽  
Colleen Lucke ◽  
Feng Lin ◽  
...  

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2551-2556 ◽  
Author(s):  
Bart R. De Geest ◽  
Sophie A. Van Linthout ◽  
Désiré Collen

Adenoviral transfer of human apo A-I in Balb/c mice induces a strong humoral immune response against the transgene product when expression is driven from the ubiquitously active CMVpromoter but induces no immune response when driven by the hepatocyte-specific 256–base pair apo A-I promoter. Here the hypothesis was tested, which is that the humoral immune response against the circulating transgene product correlates with its expression in antigen-presenting cells. No humoral immune response was observed after adenoviral transfer of vectors with human apo A-I expression driven by the hepatocyte-specific apo C-II or 1.5-kilobase (kb) humanα1-antitrypsin promoter, but antibodies were induced after transfer with vectors driven by the ubiquitously activeU1b promoter and the murine MHCII Eβpromoter. A strict correlation was observed between antigen expression in the spleen and the occurrence of an immune response. Coinjection of the 1.5-kb human α1-antitrypsin and the murine MHCII Eβ promoter–driven vectors resulted in a very short-lived humoral immune response against human apo A-I, suggesting that the time course of human apo A-I expression is a critical determinant of the development of tolerance for human apo A-I. High titers of antibodies against human apo A-I after subcutaneous gene transfer with the MHCII Eβ promoter–driven vector underscore the potential of this promoter for vaccination purposes. In conclusion, humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells.


Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4250-4261 ◽  
Author(s):  
Thaidra Gaufin ◽  
Rajeev Gautam ◽  
Melissa Kasheta ◽  
Ruy Ribeiro ◽  
Erin Ribka ◽  
...  

AbstractWe investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.


Author(s):  
Nadeem A. Sheikh ◽  
Corazon P. dela Rosa ◽  
Ling-Yu Kuan ◽  
Frances P. Stewart ◽  
Mark W. Frohlich ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. 6-21 ◽  
Author(s):  
Mehdi kheirollahpour ◽  
Mohsen Mehrabi ◽  
Naser Mohammadpour Dounighi ◽  
Mohsen Mohammadi ◽  
Alireza Masoudi

In spite of the progress of conventional vaccines, improvements are required due to concerns about the low immunogenicity of the toxicity, instability, and the need for multiple administrations of the vaccines. To overcome the mentioned problems, nanotechnology has recently been incorporated into vaccine development. Nanotechnology increasingly plays an important role in vaccine development nanocarrier-based delivery systems that offer an opportunity to increase the cellular and humoral immune responses. The use of nanoparticles in vaccine formulations allows not only enhanced immunogenicity and stability of antigen, but also targeted delivery and slow release. Over the past decade, nanoscale size materials such as virus-like particles, liposomes, ISCOMs, polymeric, inorganic nanoparticles and emulsions have gained attention as potential delivery vehicles for vaccine antigens, which can both stabilize vaccine antigens and act as adjuvants. This advantage is attributable to the nanoscale particle size, which facilitates uptake by Antigen- Presenting Cells (APCs), then leading to efficient antigen recognition and presentation. Modifying the surfaces of nanoparticles with different targeting moieties permits the delivery of antigens to specific receptors on the cell surface, thereby stimulating selective and specific immune responses. This review provides an overview of recent advances in nanovaccinology.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4884-4884
Author(s):  
Karrune Woan ◽  
Axel Heiser ◽  
Philipp Dahm ◽  
Johannes Vieweg ◽  
Zhen Su

Abstract We have previously shown that vaccination with RNA-transfected DC is a potent strategy to stimulate CTL and antitumor immunity in cancer patients. In this study, we investigated whether novel transfer peptides derived from the RNA-binding region of the HIV-1 nucleocapsid protein could be utilized for effective delivery of mRNA into human monocyte-derived dendritic cells (DC). Here we show that both peptide-mediated mRNA delivery and electroporation of DC with mRNA resulted in efficient gene transfer. However, the use of transfer peptides led to prolonged antigen expression and did not negatively affect the viability of DC, the migratory capacity of matured DC, and the production of cytokines by these cells in vitro. In murine studies, DC loaded with transfer peptide-mRNA complexes were clearly superior, compared to mRNA-electroporated DC, in stimulating antigen-specific CTL, CD4+ T cell, and antibody responses. Importantly, no transfer peptide-specific cellular or humoral immune responses were detected in vaccinated mice. Our data suggest that vaccination with transfer peptide-mRNA-loaded DC may represent a promising strategy to stimulate potent anti-tumor immune responses in a vaccination setting.


Sign in / Sign up

Export Citation Format

Share Document