A DNA Vaccine Strategy for Effective Antibody Induction to Pathogen-Derived Antigens

Author(s):  
Jason Rice ◽  
Myron Christodoulides
2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Abolfazl Mirzadeh ◽  
Geita Saadatnia ◽  
Majid Golkar ◽  
Jalal Babaie ◽  
Samira Amiri ◽  
...  

: Toxoplasmosis is a worldwide infection that can lead to serious problems in immune-compromised individuals and fetuses. A DNA vaccine strategy would be an ideal tool against Toxoplasma gondii. One of the necessary measures to provide an effective vaccine is the selection of proteins with high antigenicity. The SAG1-related sequence 3 (SRS3) protein is a major surface antigen in T. gondii that can be used as a vaccine candidate. In the present study, bioinformatics and computational methods were utilized to predict protein characteristics, as well as secondary and tertiary structures. The in silico approach is highly suited to analyze, design, and evaluate DNA vaccine strategies. Hence, in silico prediction was used to identify B and T cell epitopes and compare the antigenicity of SRS3 and other candidate genes of Toxoplasma previously applied in the production of vaccines. The results of the analysis theoretically showed that SRS3 has multiple epitopes with high antigenicity, proposing that SRS3 is a promising immunogenic candidate for the development of DNA vaccines against toxoplasmosis.


2020 ◽  
Vol 3 (2) ◽  
Author(s):  
Wiwien Mukti Andriyani ◽  
Sri Murtini ◽  
Alimuddin Alimuddin

Viral nervous necrosis (VNN) is a disease that often infects groupers. It has caused mass death in more than 34 species of marine fish. DNA vaccination might become a solution againts the infection. The construction of the pmBA-CP DNA vaccine consisting of the beta-actin promoter of medaka fish (Oryzias latipes) and capsid protein (CP) encoding VNN RNA2 has been made in previous studies. This study aimed to test the efficacy of the pmBA-CP DNA vaccine for VNN. The experiment consisted of two stages, namely (1) detection of anti-VNN antibody induction in vaccinated fish using ELISA, and (2) challenge test for fish vaccinated with the VNN virus. Grouper (body length 8 cm to 10 cm) were divided into two groups with a density of 5 fish 60 L–1. The fish in the first group were vaccinated with pmBA-CP intramuscularly at a dose of 12.5 µg per fish, while the second group of fish were not vaccinated. Antibody titer testing was carried out before treatment, and 1 d, 7 d, 14 d, 21 d, 28 d, and 35 d after vaccination. The challenge test was carried out on the 60th day after vaccination. The results showed that the S / P ratio in the vaccinated fish serum was higher than unvaccinated fish at 21 d to 35 d post-vaccination. DNA vaccination was able to induce anti-VNN antibodies of grouper. The results of the challenge test for vaccinated fish using VNN virus titer 103.5 FID50/0.2 mL showed 60% of survival rate. Thus, the pmBA-CP DNA vaccine could be useful for increasing grouper immunity, and support production of grouper.


Vaccine ◽  
2008 ◽  
Vol 26 (21) ◽  
pp. 2647-2656 ◽  
Author(s):  
Yanmin Li ◽  
Catrina M.A. Stirling ◽  
Michael S. Denyer ◽  
Pippa Hamblin ◽  
G. Hutchings ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 96 ◽  
Author(s):  
Rodolfo Garza-Morales ◽  
Jose Perez-Trujillo ◽  
Elvis Martinez-Jaramillo ◽  
Odila Saucedo-Cardenas ◽  
Maria Loera-Arias ◽  
...  

The SA-4-1BBL, an oligomeric novel form of the natural ligand for the 4-1BB co-stimulatory receptor of the tumor necrosis factor (TNF) superfamily, as a recombinant protein has potent pleiotropic effects on cells of innate, adaptive, and regulatory immunity with demonstrated therapeutic efficacy in several tumor models. However, the production of soluble form of SA-4-1BBL protein and quality control is time and resource intensive and face various issues pertinent to clinical development of biologics. The present study sought to take advantage of the simplicity and translatability of DNA-based vaccines for the production and delivery of SA-4-1BBL for cancer immune prevention and therapy. A chimeric HPV-16 E7 DNA vaccine (SP-SA-E7-4-1BBL) was constructed that contains the signal peptide (SP) of calreticulin (CRT), streptavidin (SA) domain of SA-4-1BBL, HPV-16 E7 double mutant gene, and the extracellular domain of mouse 4-1BBL. Immunization by gene gun with SP-SA-E7-4-1BBL induced greater prophylactic as well as therapeutic effects in C57BL/6 mice against TC-1 tumor model compared with immunization with E7wt, SP-SA-4-1BBL or reference-positive control CRT-E7wt. The therapeutic efficacy of the DNA vaccine was associated with increased frequency of E7-specific T cells producing interferon (IFN)-γ. Overall, our data suggest that this DNA-based vaccine strategy might represent a translational approach because it provides a simpler and versatile alternative to a subunit vaccine based on SA-4-1BBL and E7 proteins.


2000 ◽  
Vol 74 (7) ◽  
pp. 3427-3429 ◽  
Author(s):  
Jong J. Kim ◽  
Joo-Sung Yang ◽  
Thomas C. VanCott ◽  
Daniel J. Lee ◽  
Kelledy H. Manson ◽  
...  

ABSTRACT An important limitation of DNA immunization in nonhuman primates is the difficulty in generating high levels of antigen-specific antibody responses; strategies to enhance the level of immune responses to DNA immunization may be important in the further development of this vaccine strategy for humans. We approached this issue by testing the ability of molecular adjuvants to enhance the levels of immune responses generated by multicomponent DNA vaccines in rhesus macaques. Rhesus macaques were coimmunized intramuscularly with expression plasmids bearing genes encoding Th1 (interleukin 2 [IL-2] and gamma interferon)- or Th2 (IL-4)-type cytokines and DNA vaccine constructs encoding human immunodeficiency virus Env and Rev and simian immunodeficiency virus Gag and Pol proteins. We observed that the cytokine gene adjuvants (especially IL-2 and IL-4) significantly enhanced antigen-specific humoral immune responses in the rhesus macaque model. These results support the assumption that antigen-specific responses can be engineered to a higher and presumably more desirable level in rhesus macaques by genetic adjuvants.


2018 ◽  
Vol 150 ◽  
pp. 174-182 ◽  
Author(s):  
Dong-Bo Jiang ◽  
Jin-Peng Zhang ◽  
Lin-Feng Cheng ◽  
Guan-Wen Zhang ◽  
Yun Li ◽  
...  

2020 ◽  
Author(s):  
Yuting Pan ◽  
Renyong Jia ◽  
Juping Li ◽  
Mingshu Wang ◽  
Shun Chen ◽  
...  

Abstract Background Tembusu virus (TMUV), a newly emerging pathogenic flavivirus, is acute and spreads rapidly which causes massive economic losses in the Chinese duck industry. Vaccination is the most effective method to prevent TMUV. So, it’s urgent to look for an effective vaccine strategy against TMUV. Heterologous prime-boost regimen priming with DNA vaccine and boosting with recombinant adenovirus vaccine have been proven to be the successful strategy in protecting against virus in experimental animal models. Methods In this study, heterologous and homologous prime-boost strategies using DNA vaccine and recombinant adenovirus vaccine expressing prM-E or E protein of TMUV were evaluated to protect ducks against the infection of TMUV for the first time, including priming and boosting with DNA vaccine, priming and boosting with recombinant adenovirus vaccine, and priming with DNA vaccine and boosting with recombinant adenovirus vaccine. Humoral and cellular immune responses were detected and evaluated. We then challenged the ducks with TMUV at 12 days after boosting to assay for the clinical symptoms, mortality, viral loads and histopathological lesions of these different strategies. Results Comparing with homologous prime-boost strategies, higher levels of specific antibodies against E protein and the neutralizing antibodies against TMUV were detected in heterologous prime-boost regimen. And also, it could induce higher levels of IFN-γ than homologous prime-boost strategies in the later stage. Interestingly, heterologous prime-boost strategy induced higher level of IL-4 in the early stage, but gradually decreased and was even lower than homologous prime-boost strategy in the later stage. Moreover, the heterologous prime-boost strategy could efficiently protect ducks with low viral tiers, no clinical symptoms and histopathological lesions in this experiment after challenging with TMUV while slight clinical symptoms and histopathological lesions were observed in homologous prime-boost strategies. Conclusions Our results indicated that the heterologous prime-boost strategy induced higher levels of humoral and cellular immune responses and better protection against the TMUV infection in ducks than the homologous prime-boost strategies, suggesting that heterologous prime-boost strategy is an important candidate for the design of a novel vaccine strategy against TMUV.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 605
Author(s):  
Joseph Hokello ◽  
Adhikarimayum Lakhikumar Sharma ◽  
Mudit Tyagi

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable side effects such as lipodystrophy and endocrine dysfunctions, which result in HAART intolerability. HAART is also not curative. Furthermore, new HIV infections continue to occur globally at a high rate, with an estimated 1.7 million new infections occurring in 2018 alone. Therefore, there is still an urgent need for an affordable, effective, and readily available preventive vaccine against HIV/AIDS. Despite this urgent need, however, progress toward an effective HIV vaccine has been modest over the last four decades. Reasons for this slow progress are mainly associated with the unique aspects of HIV itself and its ability to rapidly mutate, targeting immune cells and escape host immune responses. Several approaches to an HIV vaccine have been undertaken. However, this review will mainly discuss progress made, including the pre-clinical and clinical trials involving vector-based HIV DNA vaccines and the use of integrating lentiviral vectors in HIV vaccine development. We concluded by recommending particularly the use of integrase-defective lentiviral vectors, owing to their safety profiles, as one of the promising vectors in HIV DNA vaccine strategies both for prophylactic and therapeutic HIV vaccines.


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