The document discusses various types of medical immunobiological preparations (MIBP) used for active and passive immunity. It describes different types of vaccines including live attenuated, killed/inactivated, subunit/split, molecular, and modern recombinant vaccines. Live vaccines induce prolonged immunity but have greater safety risks, while killed/inactivated vaccines are safer but require adjuvants and booster doses. Newer approaches to vaccines include recombinant vectors, synthetic peptides, DNA vaccines, and edible vaccines produced in transgenic plants. MIBP also include immune antisera, immunoglobulins, hyperimmune plasma, and immunomodifiers to help induce immunity.
1. Sechenov First State Medical University, Moscow
Microbiology, Virology & Immunology Department
MEDICAL IMMUNOBIOLOGICAL PREPARATIONS
for ACTIVE and PASSIVE IMMUNITY
by Yelena V. Budanova
M.D., Associate Professor
2. ‘Never in the history of human progress has a
better and cheaper method of preventing illness
been developed than immunization at its best’
(Geoffrey Edsall, pathologist)
3. INTRODUCTION
• Immunity is the resistance of the
organism to invasion by microbe and
damage by foreign substance
• There are innate (=inherent) and acquired
immunity types
• Acquired immunity can be natural or artificial
• Both are divided into active and passive
• Adaptive immunity results when lymphoid cells
are transferred from another individual
4. Acquired immunity
Natural Artificial
Active Passive Active Passive
results from
natural
infection –
“post-
infectious”
immunity
follows by
passage of
maternal IgG
through
placenta or
transfer of IgA
from mother’s
breast milk or
colostrum
is due to
vaccination
is due to
introducing of
presynthesized
antibodies or
sensitized
lymphocytes
from another
individual or
animal
5. Immunization
• Immunization is the process
rendering a host immune
• It can be active (due to vaccination) or
passive
• Medical immune biological preparations (MIBP)
can help to make person immune
• Immune biological preparations
are biologically active substances
that can specifically effect immune
system
8. VACCINES
• Vaccine is a preparation of microbes or
toxoids that can no longer induce disease
but can still stimulate active immunity
against the corresponding pathogen or its
toxin
• Vaccine is any preparation intended for active
immunological prophylaxis, preparation of killed microbes of
virulent strains or living microbes of attenuated (variant or
mutant) strains, or microbial, plant, metazoan or products
[Stedman's Concise Medical Dictionary]
• It is an antigen
• Vaccine can induce antibacterial, antiviral or
antitoxic immunity, or immunity against parasites
• Vaccine (latin “vacca” = cow, vaccinus=relating to a cow)
9. Variolation
• Variola = smallpox
• The ancient practice of ‘variolation’ dates back
to 10th
century China and arrived in Europe in
the early 18th
century
• Variolation is a technique involved inoculation
of children with dried material from healed
scabs of mild smallpox cases
• It was inconsistent and dangerous
10. Edward Jenner (1749-1823)
• The English physician
• The founder of modern
vaccination
• He has shown that more
reliable protection could be
obtained by inoculation with
cowpox (vaccinia) virus
• In 1796 E.Jenner tested his
theory by inoculating 8-year-
old boy
11. The first vaccination
• Milkmaids exposed to
cowpox virus were
traditionally resistant to
smallpox
• On the picture: E. Jenner
administers the first
vaccine to 8-year-old
James Phipps using pus
from a milkmaid’s cowpox
lesion
• This procedure protected
this child from smallpox
(he has been inoculated with
smallpox virus later)
12. • People naturally acquired
smallpox by exposure to the
smallpox virus shed from
persons with the disease. If a
person survived he/she
developed immunity to
disease
• The smallpox and cowpox
viruses have similar surface
antigens, so the vaccinated
person became immune to
both smallpox and cowpox
13. Louis Pasteur (1822-1895)
• A French Scientist known as a
founding father of Microbiology
• He has given a name “vaccine”
• He attenuated chicken cholera
pathogens to cause immunity
without inducing disease
• In 1881 he made a vaccine against
anthrax in domestic animals
• In 1885 he inoculated a 9-year-old
boy bitten by a rabid dog with
attenuated rabies vaccine made from
the dried spinal cord of infected
rabbits. A boy survived
14. VACCINATION
• Vaccination is the act of
administering vaccine by inoculating
it into the human body
• The principle of vaccination is simple:
to induce a “prime” state so that on first contact
with the relevant pathogen a RAPID and
EFFECTIVE SECONDARY IMMUNE RESPONSE
will be mounted leading to prevention of disease
• It is called the immunologic memory phenomenon
15. IMMUNOLOGIC MEMORY
• The main steps in the active immunity development:
Vaccine is inoculated by a shot or spray
Human organism makes antibodies and memory cells against the
antigen in the vaccine
Antibodies can fight the real disease if the person is exposed to the
pathogen
Antibodies and memory cells stay on guard in the body for years
after the vaccination
16. The Main Aims of Vaccination
• To prevent symptoms of the disease
• To block the pathogen transmission in a population
• To generate herd immunity (i.e., making a human
population immune)
• To eradicate the disease (the most ambitious )
17. • In the mid-1960-s, the WHO launched a programme to eradicate
smallpox
• It was the first and only absolute success against disease
• In October, 1977, the last naturally acquired smallpox was reported
• With the recovery of this patient from Somalia (pic.) smallpox was
eradicated from the Earth
18. Three Major Infectious Killers
organismorganism diseasedisease estimated annualestimated annual
deaths (millions)deaths (millions)
HIVHIV AIDSAIDS 2.62.6
MycobacteriumMycobacterium
tuberculosistuberculosis
TuberculosisTuberculosis 1.51.5
Plasmodium sp.Plasmodium sp. MalariaMalaria 1.11.1
TOTAL 5.2TOTAL 5.2
19. The REQUIREMENTS for the EFFECTIVE VACCINE and
VACCINE STRAIN
• Protective effect (=high immunogenicity)
• Safety that includes:
low virulence
low side effects (=no complications)
low harm
low allergic effect (=low ‘reactogenic’)
low teratogenic and
low oncogenic effects
• Purity and stability of antigens
• Low cost
20. l i v e
c e l l u l a r o r
v i r a l
( k i l l e d )
s u b c e l l u l a r
o r s u b v i r a l
f r a c t i o n s
( s u b u n i t )
c o r p u s c u l a r
( p a r t i c u l a t e )
p r o d u c e d b y
b i o s y n t h e s i s :
( t o x o i d s )
p r o d u c e d b y
p e p t i d e s y n t h e s i s
( s y n t h e t i c
p e p t i d e s )
p r o d u c e d b y
g e n e c l o n i n g
( r e c o m b i n a n t
v a c c i n e v e c t o r s )
m o l e c u l a r
n o n - l i v e
( i n a c t i v a t e d )
v a c c i n e s
TYPES of VACCINES (see the Manual!)
21. CLASSIFICATION of VACCINES
by the NATURE of ANTIGEN
• Live vaccines: contain alive but weakened
microbes that are less virulent to human
divergent vaccines (e.g., smallpox vaccine)
(comes from “divergency” - a moving or spreading apart or in
different directions; the condition of being unlike or
dissimilar)
attenuated (e.g., BCG vaccine)
selective (e.g., oral Sabin poliomyelitis
vaccine)
recombinant (e.g., live influenza vaccine)
22. CLASSIFICATION of VACCINES
by the NATURE of ANTIGEN
• Non-live vaccines (inactivated) : contain
killed microbes of virulent strains, their
derivatives or products
killed (e.g., Salk poliomyelitis vaccine)
subunit (e.g., Hib vaccine)
split (e.g., Influenza vaccine)
molecular (e.g., toxoids, DT-vaccine)
recombinant (e.g., hepatitis B vaccine)
23. CLASSIFICATION of VACCINES
by the QUANTITY of ANTIGENS
• Monovalent vaccines (e.g., BCG)
• Polyvalent or associated vaccines (e.g.,
pentatoxoid, etc.)
• Combined vaccines (e.g., combined
cholera vaccine)
24. LIVE VACCINES
• contain living microbes
• permit replication of the microbe in the host,
increasing antigenic stimulation
• cause vaccine-induced mild infection mimicking
the early stages of natural infection
25. LIVE VACCINES
Advantages: They
• induce prolonged immunity
• usually do not require booster vaccination
• are usually administered via ‘natural way’
(non-invasive procedure)
• stimulate local (mucosal) and systemic
immunity
(NOTE: if given locally, e.g., per os, per nose)
• can be shed in a population
(NOTE: i.e., they induce “immunity in a community”)
26. LIVE VACCINES
Disadvantages: They have safety problems due to:
• insufficient attenuation;
• risk of reversion to wild strain;
• possible contamination by living microbes or toxins;
• high risk of vaccine-associated infection;
• low stability;
• requirements of the “cold chain” between the
factory and the clinic
NB: Live vaccines cannot be
administered to
immunocompromised persons!!!
27. LIVE VACCINES: methods of attenuation
– Serial passages in cells cultured in vitro
– Serial passage in nutrient culture media under
unfavorable conditions
– Adaptation to low temperatures
– Selection of spontaneous mutants
– Chemical mutagenesis
28. The Oral Polio Vaccine
• Live attenuated vaccine was originally produced by allowing
viruses to grow in unusual conditions and selecting the
randomly occurring mutants that had lost virulence
29. KILLED VACCINES
• contain microbes that have been inactivated by
chemical or physical means
• also termed a ’particulate’ or ‘corpuscular’
vaccines, because contain a whole particle of a
pathogen
31. KILLED VACCINES
Advantages: they
• are safe
• cannot reverse to a wild strain
• sterile
• stable during storage
• can be given to immunocompromised
people
• are easily produced
• rather cheap
32. KILLED VACCINES
Disadvantages:
Low immunogenic
Require booster injections
Require using of adjuvants
Cannot induce local immunity
Potential safety problems include:
Contamination by live microbes or toxins
Allergic or autoimmune reactions
Incomplete killing of a pathogen
33. SUBUNIT and SPLIT VACCINES
• contain purified protective antigens of microbes
isolated by chemical means or by splitting a viral
particle
34. SUBUNIT and SPLIT VACCINES
Advantages: cannot cause allergic or autoimmune
reactions
• safe
• cannot reverse to a wild strain
• sterile
• stable during storage
• can be given to immunocompromised people
• of low cost
• polyvalent or combined vaccines can be prepared to
shorten the number of injections
35. SUBUNIT and SPLIT VACCINES
Disadvantages:
Low immunogenic
Contain T-cell-independent antigens
Fail to stimulate T-cells, that is: induce only
primary response
Ineffective in children under 2 years
Require using of adjuvants
36. Adjuvants
• Adjuvant (Latin, adjuvans=“helper”)
• Adjuvant is a substance that enhances the
immune response when injected along with
the antigen
• e.g., Aluminum hydroxide gel, Aluminum phosphate,
Calcium phosphate, etc.
• Antigen adsorbed onto the adjuvant is released slowly,
increasing and promoting antibody formation
• Is used as immunomodifier, stimulating immune
response non-specifically
• The adsorbed antigen exhibits minimal toxicity
37. Effect of Adjuvants
• Antibody response of
mice to egg albumin
• Blue symbols – egg
albumin in saline
• Red symbols – egg
albumin in Freund’s
incomplete adjuvant
39. MOLECULAR VACCINES: toxoids
• Toxoid is the molecular vaccine containing
inactivated form of bacterial exotoxin that
is antigenically identical to the active
toxin, but is not toxic
40. MOLECULAR VACCINES: toxoids
• Are prepared by the following way (Ramon method):
0.4 % formaldehyde
during 4 weeks
at 40o
C
41. MOLECULAR VACCINES: toxoids
Advantages:
• Highly immunogenic
• Safe
• Sterile
Disadvantages:
• Possible contamination by toxins
• Call for adjuvant
• May occasionally cause allergic reaction or
infiltration at the injection site
42. Live versus non-live vaccines
Live Non-live
Preparation attenuation inactivation
Administration may be natural route;
may be single dose
injection;
multiple doses
Adjuvant not required usually required
Safety may revert to virulence requires safe method of
inactivation
Heat lability requires ‘cold chain’ satisfactory
Cost high low
Duration of
immunity
usually years may be long or short
Immune
response
IgG, IgA and
cell-mediated
mainly IgG,
little or no cell-mediated
43. The Modern Vaccines: new approaches
• Recombinant and vector vaccines
• Synthetic peptides
• DNA vaccines
• Edible vaccines
44. Recombinant (vector) vaccines
• “Vector” is an organism that is
modified to include genes
from another source
• The genes coding for antigens
are inserted into a large virus,
e.g., cowpox (vaccinia) virus
• The viruses with recombinant
genome replicate and release
antigens into the host
• Another name – “piggyback
vaccine”
45. Recombinant (vector) vaccines
Advantages:
Stable
Cheap
Easy to make
Produce long-lasting protection
Stimulate both humoral and cell-mediated immunity
Disadvantages:
Continuous antigenic stimulus may lead to tolerance
or autoimmunity
Picture: Electron micrograph of purified 22 nm hepatitis B surface antigens expressed
in yeast cells
46. Synthetic peptides
• Contain chemically synthesized the amino
acid sequences of purified protein antigens
• Vaccines have been created using peptides of
HBs antigen of hepatitis В virus, S. pyogenes M
protein, diphtheria toxin, Influenza virus, etc.
• They do not contain contaminating materials
that might harm the host
47. Synthetic peptides
The problems:
Genetic non-responsiveness of some vaccine
recipients
Must contain T- and B-cells epitopes
Low immunogenic
Require a ‘carrier molecule’
Require high technology
48. DNA vaccines
• Contain purified microbial DNA with a
suitable promoter
• Promote cell-mediated immunity
• To induce immunologic memory require
booster with the protein
• Require high technology
• Are not employed currently for routine human
or veterinary use
• DNA vaccines against influenza are now
tested on animals
49. Edible vaccines
• Is the novel approach to vaccination
• Edible plant tissues are employed
• The transgenic plants - potatoes, tomatoes,
banana, and tobacco plants can be used
• It is cheap way of vaccination
• The promising results of animal experiments
(in mice) have been obtained
50. The components of vaccines
• Antigenic material (protective antigens)
• Stabilizer
• Preserving agent
• Adjuvant
51. Indications for Vaccination
Childhood immunization
Vaccination of risk groups
Immunization of occupational risk
groups
Immunization in endemic areas
Post-exposure protection
Treatment of chronic disease
52. Vaccines Used for Treatment
• Non-live inactivated (killed) vaccines
• Induce escaping intracellular parasites from cells
• Microbes outside the cell are easily engulfed by
phagocytes and come to a contact with antibodies
• Using of vaccines leads to recovery
• Are employed for treatment of chronic cases of:
Gonorrhea
Herpes simplex infections
Staphylococcal infections
Brucellosis, etc.
53. The ‘anti-vaxxers’ concern:
Possible Risk of Complications of Vaccination
vaccine complication
live measles, mumps
killed measles, RSV
Hypersensitivity
to egg antigens
to viral antigens
pertussis, measles
(1 per 100 million doses)
Convulsions, encephalitis
mumps (1 per million doses) Meningitis
rubella Arthritis
MMR Autism ???
HPV DEATH???
54. ‘Giving kids vaccines is the absolute, unambiguous standard of care’
‘You think you are protecting children
through extracts and homeopathy and
positive thoughts and Laws of
Attraction and dancing by candlelight
on a full moon? YOU AREN’T!’
56. Passive Immunization
• Is by injection of preformed antibodies of
known specificity that:
are obtained from human (homologous) or
animal (heterologous) source
(heterologous antibodies are produced
by hyperimmunization of horses or cows)
induce antitoxic, antibacterial or antiviral immunity
produce short-term protection
are used for post-exposure prophylaxis and
treatment of infectious diseases (=immunotherapy)
can be a life-saving treatment
57. a n t it o x in s
a n t is e r a
a n t it o x ic
" n o r m a l"
n o n - s p e c if ic
p o o le d
h u m a n s e r u m
s p e c if ic
im m u n o g lo b u lin s
a n t im ic r o b ia l
im m u n o g lo b u lin s m o n o c lo n a l
a n t ib o d ie s
A n t ib o d y -
c o n t a in in g
p r e p a r a t io n s
see the Manual:
58. Indications for Passive Immunization
infection source of
antibody
indication
Diphtheria Human, horse Prophylaxis, treatment
Tetanus
Varicella zoster Human Prophylaxis in
immunodeficiencies
Gas gangrene Horse Post-exposure prophylaxis
and treatmentBotulism
Leptospirosis Buffalo, ox Treatment
Rabies Human Post-exposure (+vaccine)
Hepatitis B Human Post-exposure
Hepatitis A Pooled human
immunoglobulin
Prophylaxis (travel)
Measles Post-exposure prophylaxis
59. IMMUNOMODIFIERS
(syn.: IMMUNOMODULATORS)
• Is a group of immune biological
preparations, endogenous or exogenous,
that can specifically or non-specifically
effect human immune system
• Can either stimulate immune response
(“immunostimulators”) or
• suppress the immune system –
“immunosuppressants”
(syn.: “immunodepressants”)
60. IMMUNOMODIFIERS
Endogenous immunostimulators:
Interferons
Interleukins
Thymus peptides
Myelopeptides
TNF
Chemokines
Exogenous immunostimulators:
Biological and chemical derivatives of bacterial,
animal, or plant source
Adjuvants
Vitamins A, B or C, etc.
62. ADAPTOGENES
• Is a group of preparations that can
non-specifically effect host
metabolism
• Stimulate metabolic processes
• Regulate nervous system function
• Regulate hormone balance
• Are capable to activate immune system
• May possess antimutagenic activity
• Are made of plants (e.g., ginseng)
63. Lecture Quiz
1. What infectious disease was completely
eradicated in the world due to effective
vaccination?
2. Who gave the name to vaccines?
69. Recombinant (vector) vaccines
• A variety of viruses, bacteria and eukaryotes (yeasts) can
be used for cloned genes
• Picture: A principle of inserting genes into the vaccinia
virus Ankara
70. Complications of Vaccination
• The number of
whooping cough
cases after the
introduction of mass
immunization (1958)
• Following the scare
about the possible
adverse effects of
pertussis vaccine, the
number of cases rose
(1978-1979)
71. The Effect of Vaccination on the Incidence of
Viral Diseases in USA
• The dramatic downward trend after the introduction of a vaccines
72. Global deaths from
eight vaccine-preventable diseases
Infectious disease Annual deaths
(estimated)
Poliomyelitis
Diphtheria
Pertussis
Measles
Tetanus
Haemophilus influenzae B
Hepatitis B
Yellow fever
720
5 000
346 000
888 000
410 000
400 000
900 000
30 000
73. There are no satisfactory vaccines against:
organism disease
HIV
Hepatitis C virus
Herpes simplex virus
Cytomegalovirus
Epstein-Barr virus
Rhinoviruses
Dengue virus
AIDS
Hepatitis C
Genital herpes
Effect on fetus
Glandular fever
Common cold
Dengue fever
N. gonorrhoeae
M. tuberculosis
M. leprae
T. pallidum
C. trachomatis
Gonorrhea
Tuberculosis
Leprosy
Syphilis
Trachoma, urethritis
Plasmodium spp.
Trypanosoma spp.
Malaria
Trypanosomiasis
74. Passive Immunization
• significantly reduced
the incidence of tetanus
in the early months of
the 1st
World War
• The figure shows the
incidence of tetanus per
1000 wounded soldiers
in British hospitals
during 1914-1916
75. Non-specific Cellular Immunostimulation
Microbial Coley’s toxin (filtered cultures of
Streptococci and Serratia marcescens)
BCG
Muramyl dipeptide
Prodigiosan
Pyrogenal, etc.
Endogenous Cytokines
Thymus factors (“Thymalin”, “Tactivin”)
TNF
CSF
Myelopeptides
Hormones
?Transfer factor, etc.
76. Possible Side Effects of Cytokine Therapy
Interferons Fever
Malaise
Fatigue
Muscle pains
Toxicity to kidney, liver, heart,
bone marrow
IL-2 Vascular leak syndrome that includes:
hypotension
pulmonary edema
renal failure
hepatic failure
Mental changes
Coma
TNF-α Shock
77. KILLED VACCINES
• Methods for vaccine strains inactivation
organismorganism method of inactivationmethod of inactivation
VirusesViruses::
RabiesRabies
InfluenzaInfluenza
Poliomyelitis (Salk strain)Poliomyelitis (Salk strain)
Hepatitis AHepatitis A
ß-propiolactoneß-propiolactone
formaldehydeformaldehyde
Bacteria:Bacteria:
S.typhiS.typhi
V.choleraeV.cholerae
B.pertussisB.pertussis
Y.pestisY.pestis
heat+phenol or acetoneheat+phenol or acetone
heatheat
heat or formaldehydeheat or formaldehyde
formaldehydeformaldehyde
78. Indications for Pooled Normal Human
Immunoglobulin Therapy
• The post-exposure prophylaxis of
infectious diseases
• Prevention of recurrent infections in
patients with hypogammaglobulinemia
• Common variable deficiency correction
• Chronic lymphocytic leukemia
• Post-bone marrow transplantation
• ?AIDS