Section II - Virology By Dr. Kareem Lilo
They usually do not spread beyond the regional lymph nodes EXCEPT IN THE IMMUNE
The virus has a tendency to become latent in lymphoid tissue,
The virus can be reactivated by immunosuppression.
Adenoviruses cause primary infection in:
Several distinct clinical syndromes are associated with Adenovirus infection.
e. Adenoviral infections of the immune compromised host
The most important etiological association of adenoviruses is with the respiratory diseases.
They are responsible for 5% of acute respiratory diseases in:
Two serotypes (40, 41) have been etiologically associated with infantile gastroenteritis.
Section II - Virology By Dr. Kareem Lilo
Virus particle by EM can be detected by direct examination of fecal extracts.
Detection of adenoviral antigens by ELISA.
Detection of adenoviral NA by Polymerase chain reaction: can be used for diagnosis of
Adenovirus infections in tissue samples or body fluids.
Isolation depending on the clinical disease, the virus may be recovered from throat, or
conjunctival swabs or and urine.
Isolation is much more difficult from the stool or rectal swabs
Section II - Virology By Dr. Kareem Lilo
1. Haemagglutination inhibition
2. Neutralization tests can be used to detect specific antibodies following Adenovirus infection.
1. Careful hand washing is the easiest way to prevent infection.
2. Disinfection of Environmental surfaces with hypochlorites.
3. The risk of water borne outbreaks of conjunctivitis can be minimized by chlorination of
4. Epidemic keratoconjunctivitis can be controlled by strict asepsis during eye examination.
Section II - Virology By Dr. Kareem Lilo
8.Human Immunodeficiency Virus
- H = Infects only Human beings
- I = Immunodeficiency virus weakens the immune system and increases the risk of infection
- V = Virus that attacks the body
Acquired Immune Deficiency Syndrome
- I = Weakens the Immune system
- D = Creates a Deficiency of CD4+ cells in the immune system
- S = Syndrome, or a group of illnesses taking place at the same time
When the immune system becomes weakened by HIV, the illness progresses to AIDS
Some blood tests, symptoms or certain infections indicate progression of HIV to AIDS
- Transmitted through the same routes
- Associated with similar opportunistic infections
HIV-1 is more common worldwide
HIV-2 is found in West Africa, Mozambique, and Angola
o HIV-2 is less easily transmitted
1. Direct contact with infected blood
2. Sexual contact: oral, anal, or vaginal
3. Direct contact with semen or vaginal and
Section II - Virology By Dr. Kareem Lilo
5. HIV-infected mothers to infants during
6. pregnancy, delivery, or breastfeeding
RNA virus discovered in 1983
Virus binds to specific CD4 receptor sites and then enters the cell
- Virus enters the cell nucleus
- Using integrase the virus splices itself into genome to become part of the cell’s genetic
•It is a retrovirus with two copies of single stranded RNA genome
•It uses reverse transcriptase to transform its ss-RNA genome into a ds-DNA for integration into its
Figure(2-71)HIV-1 Virus structure
Section II - Virology By Dr. Kareem Lilo
•It has marker proteins (gp120) in the protein coat that allow it to recognize specific cells in the
•The protein coat also contains MHC-I and MHC-II molecules
gag gene codes for nucleocapsid proteins
env gene codes for envelope glycoproteins, i.e. gp41 (transmembrane protein) and gp120
pol gene codes for enzymes such as reverse transcriptase, protease and integrase (Figure 2-
Other genes code for various activators and accessory proteins
HIV destroys CD4+ cells 3 ways
1. Viral replication leaves holes in cell membranes
2. Infected cells fuse with other cells
Combine to form a syncytium that destroys all affected cells .
3. Antibodies against HIV bind to the infected cells and activate the complement system, which
- All daughter cells from infected cell are infected
- Genetic codes can direct the cell to make HIV
Section II - Virology By Dr. Kareem Lilo
- Viremia (large amount of virus in blood)
- Steady state of viral load can be maintained for many years
• HIV destroys about 1 billion CD4+ T cells every day
• Immune problems start when CD4+T cell counts drop below 500 cells/μl
• While CD4 is recognized by the virus, it is not sufficient for viral attack; it needs a
• T cells: coreceptor is CXCR4, which also acts as a receptor for the chemokine SDF-1; there
is competitive inhibition between chemokine and HIV for binding; the HIV strain is
• Monocytes: coreceptor is CCR5, which is a receptor for chemokines, which also act as
competitive inhibitors to HIV; the HIV strain is called M-tropic
• T-tropic HIV strains cause syncytia: formation of giant cells as a result of fusion of cells via
the gp120 protein on viral coats.(Figure2-73)
Figure(2-73) Complete Activation of HIV
Section II - Virology By Dr. Kareem Lilo
Infection of Human Cell with HIV
• HIV gp120 surface protein binds CD4 on target cell
• Transmembrane component, gp41, binds coreceptor
• Viral genome and other proteins are able to enter the
• RT transcribes the ssRNA genome
• The next DNA strand is made, making a double
stranded DNA molecule called a provirus
• The dsDNA is transferred to the nucleus to be added to
the host genome via the viral integrase protein at HIV
Figure(2-73)Infection of Human Cell with HIV
• In a latent cell, the integrated provirus must be activates
by transcriptional factors to make genomic ssRNA and
• Host ribosomes transcribe viral mRNAs, and the proteins
are either with the genomic RNA or part of the membrane
• The membrane buds to form a viral envelope
• The mature virus is released outside the cell
• These latent cells are dangerous because they can remain
latent for long periods of time(Figure 2-75)
Figure(2-75)Activation of Provirus
Section II - Virology By Dr. Kareem Lilo
Progression from HIV infection to stage of AIDS (figure 2-76)
WINDOW PERIOD (3-12 weeks or even 6 months)
(Antibodies to HIV not yet developed, test does not capture the real status but person can infect
(Development of antibodies, can be detected in test)
Figure(2-76)Progression of HIV to AIDS
Section II - Virology By Dr. Kareem Lilo
No exclusive symptoms (mild fever or flu like features in some cases)
May take up to 10 to 12 years to reach the stage of AIDS, the period can be prolonged through
• Tests should be taken 12 weeks after high-risk behavior, repeated 6 months after an
A. ELISA: enzyme-linked immunosorbent assay
B. Western Blot: rechecks ELISA results
C. Viral load tests measure HIV in bloodstream (PCR)
Major Signs / Symptoms of AIDS:
1. Weight loss (> 10% of body weight)
2. Fever for longer than a month
3. Diarrhea for longer than a month
2. General itchy skin diseases
4. Recurring shingles (herpes zoster)
5. Long lasting, spreading and severe cold sores
6. Long lasting swelling of the lymph glands
8. Loss of intellectual capacity
• Nonnucleoside reverse transcriptase inhibitors
• Nucleoside reverse transcriptase inhibitors
Section II - Virology By Dr. Kareem Lilo
- HAART – Highly Active Antiretroviral Therapy
• Combination of three or more medications
- Atripla – newest antiretroviral
• Combination of three medications in one pill
• Lowers the amount of HIV (called viral load) by interfering with the way HIV makes copies
3Points In HIV Cell Cycle Where Replication Can be Stopped
• Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• All 3 of these treatments are usually prescribed at once. Known as HAART, the combination
of all 3 fights the ability of the virus to rapidly mutate.(Figure 2-77)
Reverse Transcriptase Inhibitors
• Reverse Transcriptase Inhibitors interfere with the reverse transcriptase (RT) enzyme that
HIV needs to make copies of itself. There are 2 types of inhibitors each working differently .
Figure (2-77) 3Points In HIV Cell Cycle Where Replication Can be Stopped
Section II - Virology By Dr. Kareem Lilo
Type 1: NRTI’s – nucleoside drugs provide faulty DNA building blocks, stopping the DNA chain
the virus uses to make copies of itself .
Type 2: NNRTI’s- non-nucleoside RT inhibitors bind RT so the virus cannot carry out its copying
Examples Include: AZT, 3TC, Combivir, Nevirapine
• Protease Inhibitors (PI), discovered in 1995, block the protease enzyme. When protease is
blocked, HIV makes copies of itself that can’t infect new cells .
• PI Side Effects: PI’s can cause high blood sugar and consequently diabetes. Another main
concern is lipodystrophy, where your body absorbs fats and nutrients in an irregular
manner. Latent HIV can hide out in these fat cells .
Can HIV be Vaccinated Against?
- HIV thrives in the presence of circulating antibodies directed against it .(Figure 2-78)
- HIV integrates itself into the host genome and may stay dormant for years. All retroviruses
- HIV mutates and can show up to 109 viruses per day, while the common cold with 100
subtypes has proven to difficult to make a vaccine for
Figure(2-78)HIV vaccine challenge agent
Section II - Virology By Dr. Kareem Lilo
• Care and concern about HIV and AIDS for those who are living with HIV, for those who are
ill, for those who have died and for those who care for and support those directly affected.
• Hope - that the search for a vaccine and cure to halt the suffering will be successful.(Figure 2-
• Support for those living with HIV, for the continuing education of those not infected, for
maximum efforts to find effective treatments, cures or vaccines, and for those who have lost
friends, family members or loved ones to AIDS.
Section II - Virology By Dr. Kareem Lilo
Viruses contribute to development of some cancers. Typically, the virus can cause genetic changes in
cells that make them more likely to become transformed .
These cancers and viruses are linked
1. Cervical cancer and the genital wart virus, HPV
2. Primary liver cancer and the Hepatitis B virus
A-Carcinogenesis B-Factors in Carcinogenesis
Figure (2-80)Human causes by viruses
Section II - Virology By Dr. Kareem Lilo
3. T cell leukaemia in adults and the Human T cell leukaemia virus(Figure 2-80)
- Diploid single-stranded RNA viruses (5-8 kb)
- Icosahedral symmetry (100 nm)
Table (2-5) Viruses Associated With Human Cancers
Section II - Virology By Dr. Kareem Lilo
Genes encoded in both directions
o Typical infectious viruses (exogenous)
- Other, unknown transmission mechanisms
o Nontransforming retroviruses
Mechanisms of Retroviral Carcinogenesis
Infection leads to uncoating in the cytoplasm
Reverse transcriptase makes a double-stranded DNA copy
The ds-DNA translocates into the nucleus where it randomly integrates in host cell
This version of the viral genome is termed the provirus
- Induce cell division - leads to copies of the viral genome in each daughter cell
- Productive infection - spread of virus to other cells.
Section II - Virology By Dr. Kareem Lilo
- Nonenveloped icosahedral (55 nm)
- Stimulate cellular DNA synthesis
- Highly restricted host range and tissue range
Only a few are known to cause cancers
Cervical cancer is the most important
Vaccine is now available (Gardasil; types 6, 11, 16, 18)
Section II - Virology By Dr. Kareem Lilo
Cause warts (abnormal cellular proliferation)
Replicate in basal stem cells and keratinocytes of the skin and mucosa
- HeLa cells are cervical cancer cells from Helen Lang (fatal)
Papillomaviruses Encode Two Structural Proteins
Region of greatest genetic conservation
- Capsid is 72 pentamers of L1
- Expressed L1 assembles into viral conformation, viral-like particles (VLPs)
L2 is minor capsid protein(Table 2-7)
Required for encapsidation of viral genome(Figure 2-82)
L1: the major structural protein. Each viral particle has 360 copies in 72 pentamers.
L2: the minor structural protein. Up to 72 copies per particle.(Figure2-81)
Figure (2-81) Papillomavirus Particle
Section II - Virology By Dr. Kareem Lilo
Table (2-8) Papilloma virus gene function
Section II - Virology By Dr. Kareem Lilo
HPV DNA integration and cervical carcinoma
Strong association between integrated HPV DNA and cervical carcinoma. (HPV-16, HPV-18,
DNA integration anywhere in chromosome
Integration upregulates E6 and E7 gene expression
Disrupts E2 function: loss transcriptional repression of E6 and E7
E6 and E7 expressed in cells from cervical carcinoma
Binds Rb (a cellular anti-oncogene), releasing E2F (a cellular transcription factor)
E6 cooperates in transformation
Stimulates degradation of p53 (a cellular anti-oncogene, transcription factor)
Unregulated expression of HPV E6 and E7 results in unregulated cell cycling (Figure 2-84)
Figure (2-84) Precursor lesions for cervical cancer
Section II - Virology By Dr. Kareem Lilo
There are no tests to detect the HPV virus.
Most people who contract HPV will never know they have it.
Having HPV does not mean you have a disease – most people don’t have any signs or
Some low risk types cause genital and anal warts.
In rare instances, the virus persists, especially the high risk types of the HPV virus that can
develop pre-cancerous lesions and cancer.(Figure2-85)(Figure2-86)(Figure2-87).
1. Absolutely no skin-to-skin sexual contact.
2. One sexual / intimate partner forever.
3. The more sexual partners, the higher the chance of contracting HPV.
4. Using condoms is excellent protection against STI, but does not cover all the skin.
5. Pap testing will detect abnormal cells.(Figure 2-88)
6. Vaccination is now available to prevent certain low risk types that cause genital warts certain
high risk types that cause cancer.
Figure(2-90) HPV Infection and Cervical Cancer
Section II - Virology By Dr. Kareem Lilo
Figure(2-87)Cervical Cancer Develop at the Transition Zone Between Squamous and Columnar Epithelium
Figure(2-86)HIV infection and cervical cancer
Section II - Virology By Dr. Kareem Lilo
Two Distinct HPV VLP Vaccines Were Developed Commercially
ASO4 Adjuvant (Aluminum + MPL)
Figure(2-88) Cervical oncogenes and cellular tumor suppressor genes in cervical cancer
Section II - Virology By Dr. Kareem Lilo
IM Injections at 0, 1 or 2, and 6 months
Prophyactic HPV Vaccines Are L1 Virus Like Particles (VLPs(
of virion neutralizing antibodies
Figure (2-89) Cervical cancer vaccine preparation
Section II - Virology By Dr. Kareem Lilo
Live Attenuated Viruses Are Not Suitable For an HPV Prophylactic Vaccine
Papillomavirus cannot be efficiently
The viral genomes contain oncogenes
Virion protein-based subunit vaccines
are preferable, if they could efficiently induce neutralizing antibodies .
The strongest evidence linking EBV and cancer formation is found in Burkitt's lymphoma
and Nasopharyngeal carcinoma(Figure2-90)
form of skin cancer that can involve internal organs. It most often is found in patients with
acquired immunodeficiency syndrome (AIDS), and can be fatal )Figure 2-91)
Figure(2-90)EBV-associated indigence
Figure (2-91) Kaposite sarcoma
Section II - Virology By Dr. Kareem Lilo
cancer that arises from hepatocytes, the major cell type of the liver .
Hepatocellular carcinoma is one of the major cancer killers .
It affects patients with chronic liver disease who have established cirrhosis, and currently is
the most frequent cause of death in these patients .
The main risk factors for its development are hepatitis B and C virus infection, alcoholism
Section II - Virology By Dr. Kareem Lilo
A vaccine is any preparation intended to produce immunity to a disease by stimulating the
production of antibodies. Vaccines include, for example, suspensions of killed or attenuated
microorganisms, or products or derivatives of microorganisms.
The most common method of administering vaccines is by injection(Figure2-92), but some
are given by mouth or nasal spray.
- Haemophilus influenzae type b (Figure 2-94)
- Meningococcal disease (Figure 2-95)
Figure (2-92)vaccine administration by injection
Section II - Virology By Dr. Kareem Lilo
Figure (2-93) This child has diphtheria and has developed a pseudo-membrane, a thick gray coating
Figure(2-94) This child has a swollen face due to Hib infection.
Section II - Virology By Dr. Kareem Lilo
Caused by the bacterium Streptococcus pneumoniae
Can infect different parts of the body leading to:
2. Bacteremia (blood infection)
Figure(2-95) This 4-month-old has gangrene due to infection with meningococcus.
Figure(2-96) Child with broken blood vessels in eyes and bruising on
face due to severe coughing caused by pertussis.
Section II - Virology By Dr. Kareem Lilo
- Inactivated vaccines also ight viruses. These vaccines are made by
- inactivating, or killing, the virus during the process of making
- the vaccine. The inactivated polio vaccine is an example of this
- type of vaccine. Inactivated vaccines produce immune responses
- in different ways than live, attenuated vaccines. Often, multiple
- doses are necessary to build up and/or maintain immunity
Figure (2-98) This child was experiencing painful muscle spasms due to infection with tetanus.
Section II - Virology By Dr. Kareem Lilo
Figure(2-98) Importance of T helper cells in an immune response: T helper cells recognize antigens
from antigen-presenting cells (APCs) and then release cytokines and activate other immune cells.
Parasitic worms influence what kinds of T helper cells are activated.
Section II - Virology By Dr. Kareem Lilo
HPV is the most common sexually transmitted disease
Most people who are infected do not have any symptoms
Pap tests are performed on females to evaluate cells from the cervix under a microscope
- Cells are examined for abnormal changes that if left untreated may develop into
Figure(2-99)This woman has a skin rash from shingles.
Figure(2-100) This photo shows how influenza germs spread through the air when
Section II - Virology By Dr. Kareem Lilo
Figure (2-101)Head and shoulders of a boy with measles
Figure(2-102) This child is very swollen under the jaw and in the cheeks due to mumps.
Section II - Virology By Dr. Kareem Lilo
Causes severe vomiting and diarrhea that can lead to dehydration.
Dehydration can lead to death particularly in countries where medical care is not readily
Before there was a vaccine virtually all children had this infection by the age of five.
1. Protect the individual from disease.
2. Reduce the severity of disease.
Figure (2-104) This child was born with cataracts caused by a rubella infection his mother
.transmitted to him before birth
Section II - Virology By Dr. Kareem Lilo
4. Eradication of the disease.
History of vaccine development (Table 2-7)
In1796 Adward Jenner, used matter from cowpox pustules to inoculate patients successfully against
smallpox, which is caused by a related virus.
By 1900, there were two human virus vaccines, against smallpox and rabies, and three bacterial
vaccines against typhoid, cholera, and plague.
During the 20th century, other vaccines that protect against once commonly fatal infections such as
developed. The initial EPI goals were to ensure that every child received protection against six
they were one year of age and to give tetanus toxoid vaccinations
to women to protect them and their newborns against tetanus.
Since then, new vaccines have become available. Some of them, such as hepatitis B, rotavirus,
influenzae type b (Hib) and pneumococcal vaccines, are recommended by the WHO for global use.
Others, such as yellow fever vaccine, are recommended in countries where disease burden data
Section II - Virology By Dr. Kareem Lilo
Regulatory and safety issues of vaccines before and after licenses
The pathogens causing the vaccine-preventable are mainly microorganisms such as bacteria or
Bacteria are single-celled life-forms that can reproduce quickly on their own.
Viruses, on the other hand, cannot reproduce on their own. They are ultramicroscopic
infectious agents that replicate themselves only within cells of living hosts.
1800–1899 1900–1949 1950–1979 1980–1999 2000
Table (2-7) History of vaccine development
Section II - Virology By Dr. Kareem Lilo
Figure(2-106) Primary and secondary immune responses to the same pathogen
– Inactivated polio virus (IPV)
– Haemophilus infuenzae type b (Hib),
– Pneumococcal (PCV-7, PCV-10, PCV-13)
Section II - Virology By Dr. Kareem Lilo
Vaccines may be monovalent or polyvalent. A monovalent vaccine contains a single strain of a single
antigen (e.g. Measles vaccine), whereas a polyvalent vaccine contains two or more strains/serotypes
of the same antigen (e.g. OPV).
Some of the antigens above can be combined in a single injection that can prevent different diseases
or that protect against multiple strains of infectious agents causing the same disease (e.g.
combination vaccine DPT combining diphtheria, pertussis and tetanus antigens). Combination
children’s fear of needles and pain.
Available since the 1950s, live attenuated vaccines (LAV) are derived from disease- causing
pathogens (virus or bacteria) that have been weakened under laboratory conditions. They will grow
in a vaccinated individual, but because they are weak, they will Live microorganisms provide
continual antigenic stimulation giving sufficient time for memory cell production. cause no or very
Attenuated pathogens have the very rare potential to revert to a pathogenic form and cause disease
disease-causing vaccine-derived poliovirus (VDPV) associated with oral polio vaccine (OPV).
If the vaccine is grown in a contaminated tissue culture it can be contaminated by other
viruses (e.g. retro viruses with measles vaccine).
Many LAVs require strict attention to the cold chain for the vaccine to be are subject to program
failure when this is not adhered to.
Protein-based subunit vaccines
Section II - Virology By Dr. Kareem Lilo
- Protein based subunit vaccines present an antigen to the immune system without viral
particles, using a specific, isolated protein of the pathogen .
- Commonly used protein-based subunit vaccines are the following:
- Acellular pertussis (aP) vaccines contain inactivated pertussis toxin (protein) and may
contain one or more other bacterial components. The pertussis toxin is detoxified either by
treatment with a chemical or by using molecular genetic techniques.
- Hepatitis B vaccines are composed of the hepatitis B virus surface antigen (HBsAg), a
protein produced by hepatitis B virus. Earlier vaccine products were produced using
purified plasma of infected individuals. This production method has been replaced by
recombinant technology that can produce HBsAg without requiring human plasma
increasing the safety of the vaccine by excluding the risk from potential contamination of
Some bacteria when infecting humans are often protected by a polysaccharide (sugar) capsule that
helps the organism evade the human defense systems especially in infants and young children.
Polysaccharide vaccines create a response against the molecules in the pathogen’s capsule. These
molecules are small, and often not very immunogenic. As a consequence they tend to:
Not be effective in infants and young children (under 18–24 months),
Induce only short-term immunity (slow immune response, slow rise of antibody levels, no immune
Examples of polysaccharide vaccines include Meningococcal disease caused by Neisseria
meningitides groups A, C, W135 and Y, as well as Pneumococcal disease.
comparison to plain polysaccharide vaccines, they benefit from a technology that binds the
polysaccharide to a carrier protein that can induce a long-term protective response even in infants.
subunit vaccines, can therefore prevent common bacterial infections for which plain polysaccharide
Section II - Virology By Dr. Kareem Lilo
The advent of conjugate subunit vaccines heralded a new age for immunization against diseases
caused by encapsulated organisms such as meningococcus, Haemophilus influenzae type b (Hib)
WHO recommends that children receive Haemophilus influenzae type b (Hib) and pneumococcal
conjugate vaccines. In addition,.
Toxoid vaccines are based on the toxin produced by certain bacteria (e.g. tetanus or diphtheria).
The toxin invades the bloodstream and is largely responsible for the symptoms of the disease. The
protein-based toxin is rendered harmless (toxoid) and used as the antigen in the vaccine to elicit
To increase the immune response, the toxoid is adsorbed to aluminium or calcium salts, which serve
Antigens are the components derived from the structure of disease-causing organisms, which are
recognized as ‘foreign’ by the immune system and trigger a protective immune response to the
can become unstable due to hydrolysis and aggregation of protein and carbohydrate molecules.
Section II - Virology By Dr. Kareem Lilo
Adjuvants are added to vaccines to simulate the production of tibodies against the vaccine to make
Adjuvants have been used for decades to improve the immune response to vaccine antigens, most
often in inactivated (killed) vaccines. In conventional vaccines, adding adjuvants into vaccine
formulations is aimed at enhancing, accelerating and prolonging the specific immune response to
Aluminium salts are among the oldest adjuvants that are commonly used. They slow the escape of
from the site of injection thereby lengthening the duration of contact between the antigen and the
immune system (i.e. macrophages and other antigen-receptive cells).
Antibiotics (in trace amounts) are used during the manufacturing phase to prevent bacterial
contamination of the tissue culture cells in which the viruses are grown. Usually only trace amounts
appear in vaccines, for example, MMR vaccine and IPV each contain less than 25 micrograms of
neomycin per dose .Persons who are known to be allergic to neomycin should be closely observed
after vaccination so that any allergic reaction can treated at once.
Preservatives are added to multidose vaccines to prevent bacterial and fungal growth. They include a
variety of substances, for example Thiomersal, Formaldehyde, or Phenol derivatives.
Section II - Virology By Dr. Kareem Lilo
The development process for vaccines is unique. Vaccine development is highly capital intensive and
risky. Given the importance of safety with biologics, the vaccine industry is highly regulated
Research to discover new vaccine antigens and novel approaches to immunization usually takes
several years, and costs tens of millions of dollars.(Table 2-8)
Once a discovery is made, several developments must be undertaken to reach the licensing stage.
The development of each of these processes is very lengthy, requiring on average 10–15 years. The
total development costs can reach close to $US1 billion
The manufacture of vaccines is achieved from the propagation of living microorganisms. Some of
these may be dangerous human pathogens. Therefore, the manufacture of vaccines is conducted in a
highly regulated and controlled environment.
All vaccine manufacturers are subject to national and international regulatory control and must
comply with specifications for Good Manufacturing Practices (GMP). These requirements vary
between countries, but the fundamentals are common .
Manufacturing is conducted in an aseptic environment and closely monitored by quality control
measures. Vaccines also require a strict cold chain to maintain their stability. Under most
circumstances vaccines are shipped and stored under refrigeration .(Table 2-9)
Table (2-8) The main steps for vaccine development
Section II - Virology By Dr. Kareem Lilo
Regulatory process for vaccines under development
Because of their biological nature and because they are largely administered to healthy individuals,
the entire vaccine development and manufacturing process is regulated.
Before vaccines are licensed, the three successive phases of clinical development must be approved
by a national regulatory authority and may only proceed from one phase to the next upon approval
The regulator has the authority to refuse or withdraw a product license if the manufacturer is not
compliant with current regulations.(Figure2-106)
Technologies for vaccine development.
Since the times of Pasteur, vaccines have been developed using empirical approaches consisting
mostly of killed or live-attenuated microorganisms, partially purified components of pathogens
(subunit vaccines), detoxified toxins or polysaccharides.
These vaccines have been very successful in eliminating many devastating diseases.
During the past 30 years, subsequent waves of new technologies have made possible vaccines that
were impossible with the empirical approaches. These include recombinant DNA technology,
glycoconjugation, reverse vaccinology and many emerging next-generation technologies, such as
novel adjuvants, synthetic biology and structure-based vaccine design (structural
Table (2-9) Vaccine meutecting steps
Figure (2-106) Regular steps for vaccine under development
Section II - Virology By Dr. Kareem Lilo
Vaccine efficacy varies according to the type of vaccine and the manner in which the vaccine antigen
is processed by the immune system.
Vaccine efficacy may also vary between different populations. However, in general, the efficacy of
licensed vaccines ranges from above 70% to almost 100.
70–100% compared to the attack rates in the unvaccinated population.
Figure(2-107) Technology for vaccine development
Section II - Virology By Dr. Kareem Lilo
Production of Licensed US Influenza Vaccines: by Growing Viral Isolates in Embryonated
Figure (2-108)Vaccine efficacy
Figure(2-109) Influenza Vaccines production steps
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