Induction of a robust immune response against avian influenza virus following transdermal inoculation with H5-DNA vaccine formulated in modified dendrimer-based delivery system in mouse model
نویسندگان
چکیده
This study was aimed to evaluate the immunogenicity of recombinant plasmid deoxyribonucleic acid (DNA), pBud-H5-green fluorescent protein (GFP)-interferon-regulatory factor (IRF)3 following delivery using polyamidoamine (PAMAM) dendrimer and transactivator of transcription (TAT)-conjugated PAMAM dendrimer as well as the effect of IRF3 as the genetic adjuvant. BALB/c mice were vaccinated transdermally with pBud-H5-GFP, PAMAM/pBud-H5-GFP, TAT-PAMAM/pBud-H5-GFP, and TAT-PAMAM/pBud-H5-GFP-IRF3. The expression analysis of H5 gene from the blood by using quantitative real-time reverse transcriptase polymerase chain reaction confirmed the ability of PAMAM dendrimer as a carrier for gene delivery, as well as the ability of TAT peptide to enhance the delivery efficiency of PAMAM dendrimer. Mice immunized with modified PAMAM by TAT peptide showed higher hemagglutination inhibition titer, and larger CD3+/CD4+ T cells and CD3+/CD8+ T cells population, as well as the production of cytokines, namely, interferon (IFN)-γ, interleukin (IL)-2, IL-15, IL-12, IL-6, and tumor necrosis factor-α compared with those immunized with native PAMAM. These results suggest that the function of TAT peptide as a cell-penetrating peptide is able to enhance the gene delivery, which results in rapid distribution of H5 in the tissues of the immunized mice. Furthermore, pBud-H5-GFP co-expressing IRF3 as a genetic adjuvant demonstrated the highest hemagglutination inhibition titer besides larger CD3+/CD4+ and CD3+/CD8+ T cells population, and strong Th1-like cytokine responses among all the systems tested. In conclusion, TAT-PAMAM dendrimer-based delivery system with IRF3 as a genetic adjuvant is an attractive transdermal DNA vaccine delivery system utilized to evaluate the efficacy of the developed DNA vaccine in inducing protection during challenge with virulent H5N1 virus.
منابع مشابه
Broadly Protective Adenovirus-Based Multivalent Vaccines against Highly Pathogenic Avian Influenza Viruses for Pandemic Preparedness
Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines a...
متن کاملImmunogenicity of Concentrated and Purified Inactivated Avian Influenza Vaccine Formulation
Avian influenza (AI) H9N2 is a low pathogenic virus subtype belonging to Orthomyxoviridae family. Given the prevalence of this subtype as an infectious agent in poultry industry, special attention has been always directed toward the development of vaccine production against this infection. The vaccine of this infection is produced by killing the virus and using a mixture of inactivated antigen ...
متن کاملGenetic Vaccines and Therapy
Background: Studies have shown that DNA vaccines can induce protective immunity, which demonstrated the high potential of DNA vaccines as an alternative to inactivated vaccines. Vaccines are frequently formulated with adjuvants to improve their release, delivery and presentation to the host immune system. Methods: The H5 gene of H5N1 virus (A/Ck/Malaysia/5858/04) was cloned separately into pcDN...
متن کاملThe Combined Use of rHVT-H5 and rHVT-F Vector Vaccines in the Hatchery Enhances Immunity against Highly Pathogenic Avian Influenza H5N1 and Velogenic Newcastle Disease Viral Infections in Commercial Chickens
Highly pathogenic avian influenza H5N1 and Newcastle disease viral infections cause severe illness in chickens and vaccination is a strategic tool of controlling these diseases. Hence, this study was conducted to evaluate the efficacy of using both recombinant herpesvirus of turkey (rHVT-H5 and rHVT-F) vector vaccines at day-old, in the hatchery, under field conditions. Vaccinated chickens were...
متن کاملExpression of HA1 antigen of H5N1 influenza virus as a potent candidate for vaccine in bacterial system
The impending influenza virus pandemic requires global vaccination to prevent large-scale mortality and morbidity, but traditional influenza virus vaccine production is too slow for rapid responses. In this study, bacterial system has been developed for expression and purification of properly folded HA1 antigen as a rapid response to emerging pandemic strains. Here, a recombinant H5N1 (A/Indone...
متن کامل