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TEKNOLOGIVAKSIN

G. M. Silvia M., dr, M. Sc

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Tujuan Pembelajaran
• Mahasiswa dapat menjelaskan
perkembangan vaksin sampai saat ini
• Mahasiswa dapat mendeskripsikan tipe
vaksin yang ideal
• Mahasiswa dapat membedakan jenis-jenis
vaksin
• Mahasiswa dapat menjelaskan mekanisme
kerja vaksin
• Mahasiswa dapat menjelaskan tahapan
pembuatan vaksin
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CONTAINS
1. Sejarah vaksin
2. Vaksin yang ideal
3. Tipe vaksin (aktif dan
pasif)
4. Mekanisme kerja
vaksin
5. Pembuatan beberapa
vaksin

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SEJARAH PERKEMBANGAN VAKSIN
• Edward Jenner (1796)
melakukan
eksperimen vaksin cacar pertama
dengan menginokulasikan ekskret
vesikel cacar ke kulit seorang anak
dari vesikel seorang
perempuan yang tertular cacar sapi.
Percobaan menghasilkan vaksin
campak tahun 1798 yang
menyelamatkan ribuan orang dari
kematian
• Vaksin berasal dari kata vacca
yang berarti sapi. 5
• Pasteur (1885) memperkenalkan
cara penanggulangan penyakit
akibat gigitan tersangka rabies
dengan menggunakan cara
vaksinasi menggunakan vaksin
anti rabies (VAR)
• VAR yang digunakan ini kemudian
mengalami perkembangan berupa
perbaikan, baik menyangkut
substrat yang digunakan maupun
yang menyangkut cara inaktivasi
dari virus hasil panen. Ini sebagai
usaha untuk mendapatkan vaksin6
yang lebih imunogenik dan lebih
• 24 April 1927, dokter Albert Calmette dan seorang peneliti
bernama Camille Guerin berhasil menemukan vaksin
untuk mengobati penyakit TBC, yang dinamakan vaksin
bacillus calmette guerin (BCG). Penelitian mereka untuk
menemukan vaksin itu telah dimulai sejak 1906 ketika
Guerin menemukan bahwa ketahanan terhadap penyakit
TBC berkaitan dengan adanya bakteri tubercle
Smallpox bacilli
(1798), rabiesyang
(1885),
hidup di dalam darah. (1897), difteri (1923), pertusis
plague
(1926),
tuberculosis/BCG (1927),
tetanus
(1927), dan yellow fever (1935).
Beberapa vaksin digunakan
secara individu di daerah dengan
risiko penyakit seperti rabies dan
plague, tetapi tidak pernah
digunakan secara sistematis
dalam skala global. Sementara
BCG telah secara meluas
PERKEMBANGAN VAKSIN
• Vaksin MMR ditemukan oleh Maurice
Hileman, adalah campuran dari tiga jenis
virus yang dilemahkan yang disuntik untuk
melawan demam campak,
parotitis/gondong, dan rubela.
Berdasarkan rekomendasi Ikatan Dokter
Indonesia, imunisasi MMR umumnya
diberikan kepada anak-anak yang
berumur 12 - 18 bulan, dengan dosis
booster diberikan sebelum memasuki
umur sekolah (sekitar umur 5 atau 6
tahun). Di Amerika Serikat, vaksin MMR
diizinkan pada tahun 1963 dan boosternya
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dimulai pada pertengahan tahun 1990-an.
PERKEMBANGAN VAKSIN
• Penemuan virus dan vaksin Hepatitis B
merupakan salah satu prestasi medis terbesar
pada abad ke20. Vaksin ditemukan oleh Baruch
Samuel Blumberg. Seorang ilmuwan dari Amerika
Serikat dan juga pemenang penghargaan Nobel
bidang Kedokteran pada tahun 1976.
Keberhasilnnya diawali dengan melakukan
penelitian pada tahun 1950 dengan melakukan
perjalanan keliling dunia untuk mengambil sampel
darah manusia dan mempelajari variasi yang
diwariskan dalam diri manusia. Penemuan antibodi
tersebut terjadi secara kebetulan pada saat
meneliti variasi kimia dalam darah pasien penderita
hemofilia yang telah seringkali menerima transfusi
darah. Akhirnya, terdeteksi suatu antigen dalam
darah seorang Aborigin Australia. Antigen ini 9
disebut Antigen Australia, yang kini lebih dikenal
PERKEMBANGAN VAKSIN
• Vaksin Hep B rekombinan ditemukan
pada awal tahun 2000 oleh profesor
Biokimia dari Chile, Pablo DT Valenzuela
(sekarang berusia 74 tahun).
• Vaksin rotavirus ditemukan oleh H. Fred
Clark dan Paul Offit tahun 1998, vaksin
RotaTeq, yang merupakan vaksin penta
valent (Penta Valent Vaccine / yang
sering disingkat menjadi PRV), yang
dikembangkan dari reassortan rotavirus
manusia dan rotavirus sapi, yang
setelah sukses menjalankan uji klinik yang
melibatkan 70.000 bayi dan didaftarkan10
resmi untuk dipergunakan di Amerika
PERKEMBANGAN VAKSIN
• Vaksin tetravalen Dengue (Dengvaxia,
Sanofi Pasteur) diterima oleh CDC pada
Desember 2015, sebagai pencegahan
terhadap Dengue fever pada usia 9 – 45
tahun di daerah endemik. Vaksin ini telah
melalui 25 kali uji klinik di 15 negara,
melibatkan 30.000 orang.
• Vaksin yang masih dalam tahap
penelitian: malaria (Mosquirix, GSK, phase
3), HIV/AIDS (www.hvtn.org), dan
tuberkulosis

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IDEAL VACCINE
• Should give life-long immunity
• Should be broadly protective against all variants of an
organism
• Should prevent disease transmission, e.g. by preventing
shedding
• Should induce effective immunity rapidly
• Should be effective in all vaccinated subjects, including
infants and the
elderly
• Should transmit maternal protection to the fetus
• Requires few (ideally one) immunizations to induce
protection 13
HERD IMMUNITY (KEKEBALAN
KELOMPOK)
• Daya tahan kelompok atau kelompok
masyarakat terhadap masuknya dan
menyebarnya agen infeksi karena
sebagian besar anggota kelompok
tersebut memiliki daya tahan terhadap
infeksi.
• Kekebalan kelompok disebabkan oleh
menurunnya peluang penularan bibit
penyakit dari penderita yang terinfeksi
kepada orang sehat yang rentan bila 14
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TYPES OF ACTIVE VACCINES:
1. LIVE/ATTENUATED VACCINE
• Live vaccines are prepared from live organisms. These
organisms are passed through chick embryos or other such
media repeatedly till they lose their capacity to induce the
disease fully, but retain the capacity to trigger off the defence
mechanism. Live vaccines are usually more potent than
inactivated vaccines. They multiply within the host and
produce more antigens.
• Live vaccines should not be given to people with immune
deficiency or people being treated for certain chronic
ailments or pregnant women (unless absolutely
necessary).
• Live virus vaccines are used for tuberculosis ( BCG),
measles, polio. Usually one dose of live vaccine is enough
for immunity. Some, as in the case of polio, need more.
storage 16
Effective storage is crucial for live vaccines. Do not
facility.
2. KILLED/INACTIVATED
VACCINE
• Certain organisms when killed by heat or chemicals and
then introduced into the body induce immunity. Killed
vaccines are not as effective as live vaccines. For
instance the pertussis vaccine, after three doses is
about 80% effective in the first three years and after 12
years not at all. Inactivated vaccines may require two
or three doses. These are administered by injections.
• Diphtheria, pertussis, tetanus, cholera, rabies,
hepatitis A and hepatitis B are some diseases that
are combated with killed vaccines.

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3. TOXOID
VACCINE
Toxoid vaccines are made from inactivated toxic
compounds that cause illness rather than the micro-
organism. Examples of toxoid- based vaccines include
tetanus and diphtheria. Toxoid vaccines are known for
their efficacy. Not all toxoids are for micro-organisms; for
example, Crotalus atrox toxoid is used to vaccinate dogs
against rattlesnake bites.

4. CELLULAR FRACTION/SUBUNIT VACCINE


Some vaccines are prepared from fractions of the cell.
The meningococcal vaccine is produced from the
polysaccharide antigen on the cell wall. These vaccines
are safe and effective but for a limited duration.
Examples include the subunit vaccine against Hepatitis B virus that
is composed of only the surface proteins of the virus (previously
against
extractedhuman
from papillomavirus
the blood serum(HPV) that is composed
of chronically of the but 18
infected patients,
viral
protein,
major
andcapsid
now produced thebyhemagglutinin
recombinationand
of neuraminidase
the viral genes subunits of the
into yeast), the
5.CONJUGATE VACCINE
Certain bacteria have polysaccharide outer coats that
are poorly immunogenic. By linking these outer coats to
proteins (e.g. toxins), the immune system can be led to
recognize the polysaccharide as if it were a protein
antigen. This approach is used in the Haemophilus
influenzae type B vaccine.

6.COMBINATION VACCINE
This is a mix of two or more types of vaccines. This
enables easier administration, reduces cost and avoids
repeated contact with the patient. DPT (Diphtheria,
Pertussis and Tetanus) vaccine is given in a single
shot. Some vaccines combine two strains of the same
species. Polio and influenza vaccines are prepared this
way. 19
TYPES OF PASSIVE
VACCINE/IMMUNIZATION
1. Immunoglobulin
Immunoglobulins are specific protein substances that
are produced by certain cells in the body to help in
fighting infection.
Immunoglobulins are of five different types -
Immunoglobulin G, A, M, D and E. The invading
organisms or vaccines promote the production of
immunoglobulins (antibodies) against that particular
disease-causing organism which is then destroyed. The
body also retains in its memory the template of the
disease-causing organism so that the next time it
attacks, the antibodies are quick to counter any threat
to the body and the person does not develop the 20
disease.
2. Antisera
Materials prepared in animals are called antisera. Since
human immunoglobulin preparations are not available
for all diseases, we rely on antitoxins produced from
animal sources. These are used to fight tetanus,
diphtheria, gas gangrene, snakebite and botulism.
Antisera can produce serum sickness due to the
recipient's sensitivity. So, today the preference is
toward immunoglobulins.

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HOW VACCINES WORK
1. Initiation of immune responses
2. Immunological memory
3. Appropriate immune response

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1. INITIATION OF IMMUNE RESPONSE
1.1 Danger signals
• Antigens must be recognized as foreign for an immune
response to occur. Microorganisms are usually
recognized because they carry ‘danger’ signals that
signal the immune system through conserved pattern
recognition receptors (Toll like receptors).
• Tissue damage also leads to the expression of self
molecules that can also activate cells of the innate
immune system.
• Initial recognition of microorganisms as foreign is likely
to take place in non-lymphoid tissues and the most
important cells in this process are tissue resident
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macrophages and dendritic cells (DCs).
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1.2 Antigen
processing
• Antigens entering cells by endocytosis are broken down
in lysosomal vesicles and peptides from them encounter
major histocompatiblity class II antigens (MHC II) in a
specialized intracellular loading compartment where the
peptides are loaded onto MHC II molecules for transport
to the cell surface (exogenous antigen processing)
• Antigens synthesized in the cell, as is the case for
viruses and other intracellular pathogens, are broken
down to peptides by the proteasomes and the resulting
peptides are transported into the rough endoplasmic
reticulum for loading onto MHC class I molecules
(endogenous antigen processing).
• Tissue resident DCs are active antigen processing cells 26
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1.3 Maturation and
Migration
• At the same time, the cells migrate from the tissues to
the draining
lymph nodes, a process controlled by
chemokines and their receptors
• During migration and entry of DCs into the Tcell areas of
nodes, the DCs show considerable changes in
phenotype (maturation) in addition to the up-regulation
of MHC already described. The most important is the
up-regulation of surface molecules that are important for
interaction of DCs with T-cells.
• While whole micro-organisms, even if killed, may well
deliver
appropriate signals, subunit vaccines may be poorly 28

immunogenic so that adjuvants are needed. In


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2. Immunological
Memory
• During a primary immune response, lymphocytes
proliferate and
change their phenotype.
• Memory populations of cells are, therefore, both
quantitatively and qualitatively different from those
that have not yet encountered antigen.
• Lym T: rapid production of effector cytokines such as
IFN-γ or interleukins. Primed cells express higher
levels of several adhesion molecules, such as ICAM-1
and integrins, as well as homing molecules such as
CD44, CD62L and the cutaneous lymphocyte antigen
(CLA)
• immunoglobulin divide
B-cells, the hallmark more rapidlymemory
of immunological than is the 30
3. Appropriate Immune
Response
• not all immune responses are the same: development of
neutralising antibody to viruses, or pathological, for
example the production of IgE antibody leading to
anaphylaxis
• Immune responses are influenced by many factors, but
key cells that control the functions of other immune cells
are the T helper cells
• T cell memory: both Th1 and th2
• Th1: bacteria, protozoa  cellular immune
response  acute inflammation
• Th2: parasitic agent  humoral immune response 
tends to be chronic inflammation, less acute
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HOW THE VACCINE MANUFACTURED
1. Breeding & growing up
agent

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2. Separation from
media

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3. Choosing specific strain, doing specific
treatment

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4. Quality
control

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