Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated.
Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA.
Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life.
Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2222600 | PMC |
| http://dx.doi.org/10.1186/1479-0556-5-12 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Environmental exposure to single and combined ZnO and TiO nanoparticles: Implications for rainbow trout gill immune functions and microbiota.
Chemosphere
January 2025
Research Unit in Environmental and Evolutionary Biology (URBE), Institute of Life Earth and Environment, University of Namur, 61 Rue de Bruxelles, B-5000, Namur, Belgium.
ZnO and TiO nanoparticles (NPs) are widely employed for their antibacterial properties, but their potential environmental impact is raising concerns. This study aimed to assess their single and combined effects at environmentally relevant concentrations (210 μg L) on rainbow trout (Oncorhynchus mykiss) gills microbiota and immune functions. 16S rRNA gene sequencing performed after 5 and 28 days of exposure suggests that TiO NPs had a more immediate impact on bacterial diversity, while prolonged exposure to the mixture altered community composition.
View Article and Find Full Text PDFCytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.
Cell Rep
January 2025
Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address:
Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).
View Article and Find Full Text PDFExploring the dual roles of sec-dependent effectors from Candidatus Liberibacter asiaticus in immunity of citrus plants.
Plant Cell Rep
January 2025
MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, Guangzhou Key Laboratory of Spectral Analysis and Functional Probes, College of Biophotonics, School of Optoelectronic Science and Engineering, South China Normal University, Guangzhou, 510631, China.
The three SDEs of CLas were expressed in citrus leaves by AuNPs-PEI mediated transient expression system, and promoted the proliferation of CLas and inhibited citrus immunity. Huanglongbing (HLB) is the most severe bacterial disease of citrus caused by Candidatus Liberibacter asiaticus (CLas). CLas suppress host immune responses and promote infection by sec-dependent effectors (SDEs), thus insight into HLB pathogenesis is urgently needed to develop effective management strategies.
View Article and Find Full Text PDFRevolutionizing acute myeloid leukemia treatment: a systematic review of immune-based therapies.
Discov Oncol
January 2025
Division of Hematology/Oncology, The University of Texas Health Sciences Center at Houston, McGovern Medical School, 6431 Fannin Street, MSB 5.216, Houston, TX, 77030, USA.
The established protocol for the management of acute myeloid leukemia (AML) has traditionally involved the administration of induction chemotherapy, followed by consolidation chemotherapy, and subsequent allogeneic stem cell transplantation for eligible patients. However, the prognosis for individuals with relapsed and refractory AML remains unfavorable. In response to the necessity for more efficacious therapeutic modalities, targeted immunotherapy has emerged as a promising advancement in AML treatment.
View Article and Find Full Text PDFSigma1 inhibitor suppression of adaptive immune resistance mechanisms mediated by cancer cell derived extracellular vesicles.
Cancer Biol Ther
December 2025
Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!