Displaying publications 1 - 20 of 36 in total

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  1. Fulltext The development of DNA vaccines against SARS-CoV-2
    Khalid K, Poh CL
    Adv Med Sci, 2023 Sep;68(2):213-226.
    PMID: 37364379 DOI: 10.1016/j.advms.2023.05.003
    BACKGROUND: The COVID-19 pandemic exerted significant impacts on public health and global economy. Research efforts to develop vaccines at warp speed against SARS-CoV-2 led to novel mRNA, viral vectored, and inactivated vaccines being administered. The current COVID-19 vaccines incorporate the full S protein of the SARS-CoV-2 Wuhan strain but rapidly emerging variants of concern (VOCs) have led to significant reductions in protective efficacies. There is an urgent need to develop next-generation vaccines which could effectively prevent COVID-19.

    METHODS: PubMed and Google Scholar were systematically reviewed for peer-reviewed papers up to January 2023.

    RESULTS: A promising solution to the problem of emerging variants is a DNA vaccine platform since it can be easily modified. Besides expressing whole protein antigens, DNA vaccines can also be constructed to include specific nucleotide genes encoding highly conserved and immunogenic epitopes from the S protein as well as from other structural/non-structural proteins to develop effective vaccines against VOCs. DNA vaccines are associated with low transfection efficiencies which could be enhanced by chemical, genetic, and molecular adjuvants as well as delivery systems.

    CONCLUSIONS: The DNA vaccine platform offers a promising solution to the design of effective vaccines. The challenge of limited immunogenicity in humans might be solved through the use of genetic modifications such as the addition of nuclear localization signal (NLS) peptide gene, strong promoters, MARs, introns, TLR agonists, CD40L, and the development of appropriate delivery systems utilizing nanoparticles to increase uptake by APCs in enhancing the induction of potent immune responses.

    Matched MeSH terms: Vaccines, DNA*
  2. Molecular delivery of plasmids for genetic vaccination
    Mazid R, Tan MX, Danquah MK
    Curr Pharm Biotechnol, 2013;14(6):615-22.
    PMID: 24016267
    Plasmid vaccination is a smart gene delivery application mostly achieved through the utilisation of viral or copolymeric systems as surrogated carriers in micro or nano formulations. A common polymeric protocol for plasmid vaccine formulation, which as somewhat been successful, is via the complexation of the DNA molecules with a cationic polymer, and encapsulating in a vehicular carrier polymer. Even though plasmid vaccination research has not witnessed the much anticipated success, due a number of cellular and physicochemical reasons, application of copolymeric carriers with tight functionalities is a promising strategy to optimally deliver the DNA molecules; in view of the available chemistries and physical properties that could be tuned to enable enhanced targeted delivery, uptake and specific transfection. This also enables the targeting of specific epitopes and antigen presenting cells for the treatment of many pathogenic infections and cancer. This paper provides a brief critical review of the current state of plasmid vaccines formulation and molecular delivery with analysis of performance data obtained from clinical trials.
    Matched MeSH terms: Vaccines, DNA*
  3. Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice
    Khalid K, Lim HX, Anwar A, Tan SH, Hwang JS, Ong SK, et al.
    AAPS PharmSciTech, 2024 Mar 12;25(3):60.
    PMID: 38472523 DOI: 10.1208/s12249-024-02778-x
    The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.
    Matched MeSH terms: Vaccines, DNA*
  4. Fulltext Infectious hematopoietic necrosis virus: advances in diagnosis and vaccine development
    Yong CY, Ong HK, Tang HC, Yeap SK, Omar AR, Ho KL, et al.
    PeerJ, 2019;7:e7151.
    PMID: 31341728 DOI: 10.7717/peerj.7151
    The aquaculture of salmonid fishes is a multi-billion dollar industry with production over 3 million tons annually. However, infectious hematopoietic necrosis virus (IHNV), which infects and kills salmon and trout, significantly reduces the revenue of the salmon farming industry. Currently, there is no effective treatment for IHNV infected fishes; therefore, early detection and depopulation of the infected fishes remain the most common practices to contain the spread of IHNV. Apart from hygiene practices in aquaculture and isolation of infected fishes, loss of fishes due to IHNV infection can also be significantly reduced through vaccination programs. In the current review, some of the diagnostic methods for IHNV, spanning from clinical diagnosis to cell culture, serological and molecular methods are discussed in detail. In addition, some of the most significant candidate vaccines for IHNV are also extensively discussed, particularly the DNA vaccines.
    Matched MeSH terms: Vaccines, DNA
  5. Fulltext Development of Tat-Conjugated Dendrimer for Transdermal DNA Vaccine Delivery
    Bahadoran A, Moeini H, Bejo MH, Hussein MZ, Omar AR
    J Pharm Pharm Sci, 2016 Jul-Sep;19(3):325-338.
    PMID: 27806247 DOI: 10.18433/J3G31Q
    PURPOSE: In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed.

    METHODS: First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry.

    RESULTS: TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-).  In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine.  The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (P<0.05).

    CONCLUSIONS: The findings of this study suggest that TAT-conjugated PAMAM dendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
    Matched MeSH terms: Vaccines, DNA/genetics; Vaccines, DNA/pharmacokinetics*; Vaccines, DNA/chemistry*
  6. Fulltext Mucosal genetic immunization through microsphere-based oral carriers
    Rosli R, Nograles N, Hanafi A, Nor Shamsudin M, Abdullah S
    Hum Vaccin Immunother, 2013 Oct;9(10):2222-7.
    PMID: 24051430 DOI: 10.4161/hv.25325
    Polymeric carriers in the form of cellulose acetate phthalate (CAP) and alginate (ALG) microspheres were used for encapsulation of plasmid DNA for oral mucosal immunization. Access into the intestinal mucosa by pVAX1 eukaryotic expression plasmid vectors carrying gene-coding sequences, either for the cholera enterotoxin B subunit (ctxB) immunostimulatory antigen or the green fluorescent protein (GFP), delivered from both types of microsphere carriers were examined in orally immunized BALB/c mice. Demonstration of transgene protein expression and IgA antibody responses at local mucosal sites suggest immunological response to a potential oral DNA vaccine formulated within the microsphere carriers.
    Matched MeSH terms: Vaccines, DNA/administration & dosage*; Vaccines, DNA/immunology
  7. Targeting Legumain As a Novel Therapeutic Strategy in Cancers
    Mai CW, Chung FF, Leong CO
    Curr Drug Targets, 2017;18(11):1259-1268.
    PMID: 27993111 DOI: 10.2174/1389450117666161216125344
    BACKGROUND: Recent reports indicate that the tumor microenvironment plays a pivotal role in cancer development and progression, leading to a paradigm shift in the way cancer is studied and targeted. In contrast to traditional approaches, where only tumor cells are targeted for the treatment, an emerging approach is to develop therapeutics which target the tumor microenvironment while complementing or enhancing current treatments. Legumain (LGMN) is a newly identified target which is highly expressed in the tumor microenvironment and in tumor cells, and holds potential both as a biomarker and as a therapeutic target.

    CONCLUSION: This review will be the first to summarize the expression of LGMN in common cancers, as well as its roles in tumorigenesis and metastasis. This review also discusses the current developments and future prospects of targeting LGMN through the development of DNA vaccines, azopeptides, small molecule inhibitors and LGMN activated prodrugs, highlighting the potential of LGMN as a target for cancer therapeutics.

    Matched MeSH terms: Vaccines, DNA/pharmacology; Vaccines, DNA/therapeutic use
  8. Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine
    Mohd Nor N, Musa M
    Tuberculosis (Edinb), 2004;84(1-2):102-9.
    PMID: 14670351 DOI: 10.1016/j.tube.2003.08.011
    The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.
    Matched MeSH terms: Vaccines, DNA
  9. Antigenic potential of a recombinant polyvalent DNA vaccine against pathogenic leptospiral infection
    Garba B, Bahaman AR, Zakaria Z, Bejo SK, Mutalib AR, Bande F, et al.
    Microb Pathog, 2018 Nov;124:136-144.
    PMID: 30138761 DOI: 10.1016/j.micpath.2018.08.028
    Leptospirosis is a serious epidemic disease caused by pathogenic Leptospira species. The disease is endemic in most tropical and sub-tropical regions of the world. Currently, there is no effective polyvalent vaccine for prevention against most of the circulating serovars. Moreover, development of an efficient leptospiral vaccine capable of stimulating cross-protective immune responses against a wide range of serovars remains a daunting challenge. This, in part, is associated with the extensive diversity and variation of leptospiral serovars from region to region. In this study, a multi-epitope DNA vaccine encoding highly immunogenic epitopes from LipL32 and LipL41 was designed using in-silico approach. The DNA encoding antigenic epitopes was constructed from conserved pathogenic Leptospira genes (LipL32 and LipL41). Immunization of golden Syrian hamsters with the multi-epitope chimeric DNA vaccine resulted in the production of both agglutinating and neutralizing antibodies as evidence by MAT and in-vitro growth inhibition tests respectively. The antibodies produced reacted against eight different serovars and significantly reduced renal colonization following in vivo challenge. The vaccine was also able to significantly reduce renal colonization which is a very important factor responsible for persistence of leptospires among susceptible and reservoir animal hosts. In conclusion, the leptospiral multi-epitope chimeric DNA vaccine can serve as a potentially effective and safe vaccine against infection with different pathogenic leptospiral serovars.
    Matched MeSH terms: Vaccines, DNA/administration & dosage; Vaccines, DNA/genetics; Vaccines, DNA/immunology*
  10. Fulltext Recent advances in delivery of veterinary DNA vaccines against avian pathogens
    Jazayeri SD, Poh CL
    Vet Res, 2019 Oct 10;50(1):78.
    PMID: 31601266 DOI: 10.1186/s13567-019-0698-z
    Veterinary vaccines need to have desired characteristics, such as being effective, inexpensive, easy to administer, suitable for mass vaccination and stable under field conditions. DNA vaccines have been proposed as potential solutions for poultry diseases since they are subunit vaccines with no risk of infection or reversion to virulence. DNA vaccines can be utilized for simultaneous immunizations against multiple pathogens and are relatively easy to design and inexpensive to manufacture and store. Administration of DNA vaccines has been shown to stimulate immune responses and provide protection from challenges in different animal models. Although DNA vaccines offer advantages, setbacks including the inability to induce strong immunity, and the fact that they are not currently applicable for mass vaccination impede the use of DNA vaccines in the poultry industry. The use of either biological or physical carriers has been proposed as a solution to overcome the current delivery limitations of DNA vaccines for veterinary applications. This review presents an overview of the recent development of carriers for delivery of veterinary DNA vaccines against avian pathogens.
    Matched MeSH terms: Vaccines, DNA
  11. Fulltext Advances & challenges in leptospiral vaccine development
    Bashiru G, Bahaman AR
    Indian J Med Res, 2018 Jan;147(1):15-22.
    PMID: 29749356 DOI: 10.4103/ijmr.IJMR_1022_16
    Considerable progress has been made in the field of leptospiral vaccines development since its first use as a killed vaccine in guinea pigs. Despite the fact that the immunity conferred is restricted to serovars with closely related lipopolysaccharide antigen, certain vaccines have remained useful, especially in endemic regions, for the protection of high-risk individuals. Other conventional vaccines such as the live-attenuated vaccine and lipopolysaccharide (LPS) vaccine have not gained popularity due to the reactive response that follows their administration and the lack of understanding of the pathogenesis of leptospirosis. With the recent breakthrough and availability of complete genome sequences of Leptospira, development of novel vaccine including recombinant protein vaccine using reverse vaccinology approaches has yielded encouraging results. However, factors hindering the development of effective leptospiral vaccines include variation in serovar distribution from region to region, establishment of renal carrier status following vaccination and determination of the dose and endpoint titres acceptable as definitive indicators of protective immunity. In this review, advancements and progress made in LPS-based vaccines, killed- and live-attenuated vaccines, recombinant peptide vaccines and DNA vaccines against leptospirosis are highlighted.
    Matched MeSH terms: Vaccines, DNA
  12. Fulltext Scaling-up recombinant plasmid DNA for clinical trial: current concern, solution and status
    Ismail R, Allaudin ZN, Lila MA
    Vaccine, 2012 Sep 7;30(41):5914-20.
    PMID: 22406276 DOI: 10.1016/j.vaccine.2012.02.061
    Gene therapy and vaccines are rapidly developing field in which recombinant nucleic acids are introduced in mammalian cells for enhancement, restoration, initiation or silencing biochemical function. Beside simplicity in manipulation and rapid manufacture process, plasmid DNA-based vaccines have inherent features that make them promising vaccine candidates in a variety of diseases. This present review focuses on the safety concern of the genetic elements of plasmid such as propagation and expression units as well as their host genome for the production of recombinant plasmid DNA. The highlighted issues will be beneficial in characterizing and manufacturing plasmid DNA for save clinical use. Manipulation of regulatory units of plasmid will have impact towards addressing the safety concerns raised in human vaccine applications. The gene revolution with plasmid DNA by alteration of their plasmid and production host genetics will be promising for safe delivery and obtaining efficient outcomes.
    Matched MeSH terms: Vaccines, DNA/biosynthesis*
  13. DNA vaccination with a plasmid encoding LACK-TSA fusion against Leishmania major infection in BALB/c mice
    Maspi N, Ghaffarifar F, Sharifi Z, Dalimi A, Khademi SZ
    Malays J Pathol, 2017 Dec;39(3):267-275.
    PMID: 29279589
    Vaccination would be the most important strategy for the prevention and elimination of leishmaniasis. The aim of the present study was to compare the immune responses induced following DNA vaccination with LACK (Leishmania analogue of the receptor kinase C), TSA (Thiol-specific-antioxidant) genes alone or LACK-TSA fusion against cutaneous leishmaniasis (CL). Cellular and humoral immune responses were evaluated before and after challenge with Leishmania major (L. major). In addition, the mean lesion size was also measured from 3th week post-infection. All immunized mice showed a partial immunity characterized by higher interferon (IFN)-γ and Immunoglobulin G (IgG2a) levels compared to control groups (p<0.05). IFN-γ/ Interleukin (IL)-4 and IgG2a/IgG1 ratios demonstrated the highest IFN-γ and IgG2a levels in the group receiving LACK-TSA fusion. Mean lesion sizes reduced significantly in all immunized mice compared with control groups at 7th week post-infection (p<0.05). In addition, there was a significant reduction in mean lesion size of LACK-TSA and TSA groups than LACK group after challenge (p<0.05). In the present study, DNA immunization promoted Th1 immune response and confirmed the previous observations on immunogenicity of LACK and TSA antigens against CL. Furthermore, this study demonstrated that a bivalent vaccine can induce stronger immune responses and protection against infectious challenge with L. major.
    Matched MeSH terms: Vaccines, DNA/immunology*
  14. Vaccination challenges and strategies against long-lived Toxoplasma gondii
    Loh FK, Nathan S, Chow SC, Fang CM
    Vaccine, 2019 07 09;37(30):3989-4000.
    PMID: 31186188 DOI: 10.1016/j.vaccine.2019.05.083
    Since the discovery of Toxoplasma gondii in 1908, it is estimated that one-third of the global population has been exposed to this ubiquitous intracellular protozoan. The complex life cycle of T. gondii has enabled itself to overcome stress and transmit easily within a broad host range thus achieving a high seroprevalence worldwide. To date, toxoplasmosis remains one of the most prevalent HIV-associated opportunistic central nervous system infections. This review presents a comprehensive overview of different vaccination approaches ranging from traditional inactivated whole-T. gondii vaccines to the popular DNA vaccines. Extensive discussions are made to highlight the challenges in constructing these vaccines, selecting adjuvants as well as delivery methods, immunisation approaches and developing study models. Herein we also deliberate over the latest and promising enhancement strategies that can address the limitations in developing an effective T. gondii prophylactic vaccine.
    Matched MeSH terms: Vaccines, DNA/therapeutic use
  15. Development of a DNA vaccine against chicken anemia virus by using a bicistronic vector expressing VP1 and VP2 proteins of CAV
    Moeini H, Omar AR, Rahim RA, Yusoff K
    Comp Immunol Microbiol Infect Dis, 2011 May;34(3):227-36.
    PMID: 21146874 DOI: 10.1016/j.cimid.2010.11.006
    In the present study, we describe the development of a DNA vaccine against chicken anemia virus. The VP1 and VP2 genes of CAV were amplified and cloned into pBudCE4.1 to construct two DNA vaccines, namely, pBudVP1 and pBudVP2-VP1. In vitro and in vivo studies showed that co-expression of VP1 with VP2 are required to induce significant levels of antibody against CAV. Subsequently, the vaccines were tested in 2-week-old SPF chickens. Chickens immunized with the DNA-plasmid pBudVP2-VP1 showed positive neutralizing antibody titer against CAV. Furthermore, VP1-specific proliferation induction of splenocytes and also high serum levels of Th1 cytokines, IL-2 and IFN-γ were detected in the pBudVP2-VP1-vaccinated chickens. These results suggest that the recombinant DNA plasmid co-expressing VP1 and VP2 can be used as a potential DNA vaccine against CAV.
    Matched MeSH terms: Vaccines, DNA/genetics; Vaccines, DNA/immunology*
  16. Potential DNA Vaccine for Haemorrhagic Septiceamia Disease
    Chelliah S, Velappan RD, Lim KT, Swee CWK, Nor Rashid N, Rothan HA, et al.
    Mol Biotechnol, 2020 May;62(5):289-296.
    PMID: 32185600 DOI: 10.1007/s12033-020-00244-0
    Pasteurella multocida is the main cause of haemorrhagic septicaemia (HS) outbreak in livestock, such as cattle and buffaloes. Conventional vaccines such as alum-precipitated or oil-adjuvant broth bacterins were injected subcutaneously to provide protection against HS. However, the immunity developed is only for short term and needed to be administered frequently. In our previous study, a short gene fragment from Pasteurella multocida serotype B was obtained via shotgun cloning technique and later was cloned into bacterial expression system. pQE32-ABA392 was found to possess immunogenic activity towards HS when tested in vivo in rat model. In this study, the targeted gene fragment of ABA392 was sub-cloned into a DNA expression vector pVAX1 and named as pVAX1-ABA392. The new recombinant vaccine was stable and expressed on mammalian cell lines. Serum sample collected from a group of vaccinated rats for ELISA test shows that the antibody in immunized rats was present at high titer and can be tested as a vaccine candidate with challenge in further studies. This successful recombinant vaccine is immunogenic and potentially could be used as vaccine in future against HS.
    Matched MeSH terms: Vaccines, DNA/administration & dosage*; Vaccines, DNA/immunology
  17. Fulltext Attenuated Salmonella typhimurium SV4089 as a potential carrier of oral DNA vaccine in chickens
    Jazayeri SD, Ideris A, Zakaria Z, Omar AR
    J Biomed Biotechnol, 2012;2012:264986.
    PMID: 22701301 DOI: 10.1155/2012/264986
    Attenuated Salmonella has been used as a carrier for DNA vaccine. However, in vitro and in vivo studies on the bacteria following transfection of plasmid DNA were poorly studied. In this paper, eukaryotic expression plasmids encoding avian influenza virus (AIV) subtype H5N1 genes, pcDNA3.1/HA, NA, and NP, were transfected into an attenuated Salmonella enteric typhimurium SV4089. In vitro stability of the transfected plasmids into Salmonella were over 90% after 100 generations. The attenuated Salmonella were able to invade MCF-7 (1.2%) and MCF-10A (0.5%) human breast cancer cells. Newly hatched specific-pathogen-free (SPF) chicks were inoculated once by oral gavage with 10(9) colony-forming unit (CFU) of the attenuated Salmonella. No abnormal clinical signs or deaths were recorded after inoculation. Viable bacteria were detected 3 days after inoculation by plating from spleen, liver, and cecum. Fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR) were carried out for confirmation. Salmonella was not detected in blood cultures although serum antibody immune responses to Salmonella O antiserum group D1 factor 1, 9, and 12 antigens were observed in all the inoculated chickens after 7 days up to 35 days. Our results showed that live attenuated S. typhimurium SV4089 harboring pcDNA3.1/HA, NA, and NP may provide a unique alternative as a carrier for DNA oral vaccine in chickens.
    Matched MeSH terms: Vaccines, DNA/administration & dosage*; Vaccines, DNA/genetics
  18. Fulltext Preparation, characterization, and in ovo vaccination of dextran-spermine nanoparticle DNA vaccine coexpressing the fusion and hemagglutinin genes against Newcastle disease
    Firouzamandi M, Moeini H, Hosseini SD, Bejo MH, Omar AR, Mehrbod P, et al.
    Int J Nanomedicine, 2016;11:259-67.
    PMID: 26834470 DOI: 10.2147/IJN.S92225
    Plasmid DNA (pDNA)-based vaccines have emerged as effective subunit vaccines against viral and bacterial pathogens. In this study, a DNA vaccine, namely plasmid internal ribosome entry site-HN/F, was applied in ovo against Newcastle disease (ND). Vaccination was carried out using the DNA vaccine alone or as a mixture of the pDNA and dextran-spermine (D-SPM), a nanoparticle used for pDNA delivery. The results showed that in ovo vaccination with 40 μg pDNA/egg alone induced high levels of antibody titer (P<0.05) in specific pathogen-free (SPF) chickens at 3 and 4 weeks postvaccination compared to 2 weeks postvaccination. Hemagglutination inhibition (HI) titer was not significantly different between groups injected with 40 μg pDNA + 64 μg D-SPM and 40 μg pDNA at 4 weeks postvaccination (P>0.05). Higher antibody titer was observed in the group immunized with 40 μg pDNA/egg at 4 weeks postvaccination. The findings also showed that vaccination with 40 μg pDNA/egg alone was able to confer protection against Newcastle disease virus strain NDIBS002 in two out of seven SPF chickens. Although the chickens produced antibody titers 3 weeks after in ovo vaccination, it was not sufficient to provide complete protection to the chickens from lethal viral challenge. In addition, vaccination with pDNA/D-SPM complex did not induce high antibody titer when compared with naked pDNA. Therefore, it was concluded that DNA vaccination with plasmid internal ribosome entry site-HN/F can be suitable for in ovo application against ND, whereas D-SPM is not recommended for in ovo gene delivery.
    Matched MeSH terms: Vaccines, DNA/administration & dosage*; Vaccines, DNA/immunology
  19. Cytotoxicity and immunological responses following oral vaccination of nanoencapsulated avian influenza virus H5 DNA vaccine with green synthesis silver nanoparticles
    Jazayeri SD, Ideris A, Zakaria Z, Shameli K, Moeini H, Omar AR
    J Control Release, 2012 Jul 10;161(1):116-23.
    PMID: 22549012 DOI: 10.1016/j.jconrel.2012.04.015
    DNA formulations provide the basis for safe and cost effective vaccine. Low efficiency is often observed in the delivery of DNA vaccines. In order to assess a new strategy for oral DNA vaccine formulation and delivery, plasmid encoding hemagglutinin (HA) gene of avian influenza virus, A/Ck/Malaysia/5858/04 (H5N1) (pcDNA3.1/H5) was formulated using green synthesis of sliver nanoparticles (AgNP) with polyethylene glycol (PEG). AgNP were successfully synthesized uniformly dispersed with size in the range of 4 to 18 nm with an average size of 11 nm. Cytotoxicity of the prepared AgNP was investigated in vitro and in vivo using MCF-7 cells and cytokine expression, respectively. At the concentration of -5 log₁₀AgNP, no cytotoxic effects were detected in MCF-7 cells with 9.5% cell death compared to the control. One-day-old specific pathogen-free (SPF) chicks immunized once by oral gavage with 10 μl of pcDNA3.1/H5 (200 ng/ml) nanoencapsulated with 40 μl AgNP (3.7×10⁻² μg of Ag) showed no clinical manifestations. PCR successfully detect the AgNP/H5 plasmid from the duodenum of the inoculated chicken as early as 1h post-immunization. Immunization of chickens with AgNP/H5 enhanced both pro inflammatory and Th1-like expressions, although no significant differences were recorded in the chickens inoculated with AgNP, AgNP/pcDNA3.1 and the control. In addition, serum samples collected from immunized chickens with AgNP/H5 showed rapidly increasing antibody against H5 on day 14 after immunization. The highest average antibody titres were detected on day 35 post-immunization at 51.2±7.5. AgNP/H5 also elicited both CD4+ and CD8+ T cells in the immunized chickens as early as day 14 after immunization, at 7.5±2.0 and 20±1.9 percentage, respectively. Hence, single oral administrations of AgNP/H5 led to induce both the antibody and cell-mediated immune responses as well as enhanced cytokine production.
    Matched MeSH terms: Vaccines, DNA/administration & dosage*; Vaccines, DNA/genetics; Vaccines, DNA/immunology
  20. Intranasal inoculation of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia disease
    Kang TL, Chelliah S, Velappan RD, Kabir N, Mohamad J, Nor Rashid N, et al.
    Lett Appl Microbiol, 2019 Nov;69(5):366-372.
    PMID: 31508837 DOI: 10.1111/lam.13215
    We evaluate the efficacy of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia infection through intranasal administration route by targeting the mucosal immunity. The DNA vaccine was constructed and subjected to animal study using the Sprague Dawley (SD) rat. The study was divided into two major parts: (i) active and (ii) passive immunization studies, involving 30 animals for each part. Each group was then divided into five test groups: two test samples G1 and G2 with 50 and 100 µg ml-1 purified DNA vaccine; one positive control G5 with 106  CFU per ml formalin-killed PMB2; and two negative controls, G3 and G4 with normal saline and pVAX1 vector. Both studies were conducted for the determination of immunogenicity by total white blood cell count (TWBC), indirect ELISA and histopathological changes for the presence of the bronchus-associated lymphoid tissue (BALT). Our findings demonstrate that TWBC, IgA and IgG increased after each of the three vaccination regimes: groups G1, G2 and G5. Test samples G1 and G2 showed significant differences (P DNA vaccine ABA392 can provoke mucosal immunity which makes it a potential prophylactic against HS. SIGNIFICANCE AND IMPACT OF THE STUDY: New approach of combating haemorrhagic septicaemia disease among bovines by recombinant DNA vaccine is crucial to overcome the loss of edible products from the infected bovines. DNA vaccine can potentially serve as a better immunogen which would elicit both cellular and humoral immunity, and it is also stable for its molecular reproduction. This research report demonstrates an effective yet simple way of administering the DNA vaccine via the intranasal route in rats, to provoke the mucosal immunity through the development of immunoglobulins IgA, IgG and bronchus-associated lymphoid tissue which guard as the first-line defence at the host's mucosal lining.
    Matched MeSH terms: Vaccines, DNA/administration & dosage*; Vaccines, DNA/genetics; Vaccines, DNA/immunology
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