Vaksin DNA & Subunit

dr. Rahma Ayu Larasati (Imuno

 TOR
Kemajuan dan pengembangan vaksin
pencegahan dan terapeutik untuk penyakit
infeksi berbasis vaksin DNA , vaksin subunit
Kemajuan teknologi vaksin DNA dan subunit
Kemajuan dan pengembangan formula sediaan
vaksin
Keuntungan dan kerugian teknologi terbaru
 Pendahuluan
Vaksin DNA adalah vaksin yang terdiri atas
molekul untai ganda DNA sirkuler (plasmid)
yang terdiri atas regio yang dibutuhkan untuk
seleksi dan replikasi serta sekuens eukariot
yang meregulasi suatu protein antigen.
HISTORY
1990
Structure DNA Plasmid
METHODS OF DELIVERY
Gene Gun
Bioejektor
Konvensional
Physical & Chemical
Methods
HOW DNA VACCINE WORKS
BY TWO PATHWAYS
ENDOGENOUS :- Antigenic Protein is presented by
cell in which it is produced
EXOGENOUS :- Antigenic Protein is formed in
one cell but presented by
different cell
EXOGENOUS
PATHWAY

Antigenic Protein come outside

 s e d
oc yto
h ag
P

Antigen Presenting Cell

Antigenic Peptides
Memory
T- Helper Cell
Antibodies
Cytokines
Plasma B-Cell

MHC-II
Activated B-Cell Memory B-Cell
Optimization
Strategies
ADVANTAGES
DISADVANTAGES
Limited to protein immunogen
only
Extended immunostimulation
leads to chronic inflammation
Some antigen require processing
which sometime does not occur
Safety Issues
Genetic Toxicity

Integration of DNA vaccine into host Genome

Insertional mutagenesis
Chromosome instability
Turn ON Oncogenes
Turn OFF Tumor suppressor genes
Generation of
Autoimmune diseases

Anti DNA Antibodies

Autoimmune diseases

Autoimmune Myositis
Antibiotic Resistance

Plasmid used is resistance to

antibiotics for selection

Raise the resistance to same

antibiotic in the host
Vaccines DNA Trials
CURRENT LISENCED DNA
THERAPY
 Subunit Vaccine
Subunit vaccines contain a purified
antigen instead of using whole
microorganisms.
Purified antigens could be toxoid,
subcellular fragment, or surface
molecules, which are transported by
different carriers
 Cathegory
Protein- based
 Protein Based Subunit Protein
Protein based subunit vaccines present an
antigen to the immune system without viral
particles, using a specific, isolated protein
of the pathogen.
 Examples
Acellular
Polysaccharide Subunit Vaccine
Polysaccharide vaccines create a response
against the molecules in the pathogen's capsule.
These molecules are small, and often not very
immunogenic.
Not be effective in infants and young children
(under 1824 months)
Induce only short-term immunity
Examples : Vaccines for meningococcal disease
 Conjugate Subunit Vaccine
Conjugate subunit vaccines also create a
response against the molecules in the
pathogen's capsule, and that binds the
polysaccharide to a carrier protein
Carrier protein : A protein linked to a weak
antigen to increase its immunogenicity when
used as a vaccine.
Examples: Haemophilus influenzae type b (Hib)
and pneumococcal conjugate vaccines
Medium
 Adjuvant
Particulate Delivery
Lipid Based Particulate Delivery
Liposom
Cubasome
Virosome
Archaeosome
 Polimer based particulate
Delivery
Chitosan
PLGA
 Micellar Delivery System
Micelles are nano-sized core shell
particles (<100 nm) that are formed by
self-assembly of individual amphiphilic
molecules in water
 Virus Like Particle
Virus like particles
(VLPs) consist
of viral envelope or
capsid proteins that are
produced
either in eukaryotic or
prokaryotic cell
expression systems
Bacterial Ghost
Routes Delivery
Development of HIV vaccine
 References
Angeliki Tiptiri, et al. DNA vaccines to attack cancer: Strategies for improving immunogenicity and
efficacy.Elsevier Inc. 2016
Uttam Kumar, Et Al. Dna Vaccine: A Modern Biotechnological Approach Towards Human Welfare
And Clinical Trials. International Journal Of Research In Biomedicine And Biotechnology 2013;
3(1): 17-20
WHO. Guidelines for assuring the quality and nonclinical safety evaluation of DNA vaccines.
World Health Organization WHO Technical Report Series No 941, 2007
Britta Wahren , et al. DNA Vaccines: Recent Developments and the Future . Department of
Microbiology, Tumor and Cell Biology, Karolinska Institutet, Vaccines 2014, 2, 785-796
Lei Li, et al. The future of human DNA vaccines. Adelaide Institute. 2012
Stefan HE Kaufmann, et al. Challenges and responses in human vaccine development.
sciencedirect Current Opinion in Immunology 2014, 28:1826.
Alexander von Gabain, et al. Development of Novel Vaccines . Department of Molecular Genetics
and Microbiology, Robert Wood Johnson Medical School. 2012.
Jorritsma, et al. Delivery methods to increase cellular uptake and immunogenicity of DNA
vaccines. Virology Research Group, The University of Adelaide, Australia. 2016