ANTIVIRALS AGENTS ARE:

Nucleotide analogues, Interferons, Immunoglobulin

Therapy

1-Nucleotide analogues
These are synthetic compounds which resemble
nucleosides, but have an incomplete or abnormal
deoxy-ribose /or ribose group
These compounds are phosphorylated to the tri-phosphate
form within the infected cell.

In this form, the drug competes with normal nucleotides for

incorporation into viral DNA or RNA.

Incorporation into the growing nucleic acid chain results in

irreversible association with the viral polymerase and chain
termination.
2-Interferons:
There are three classes: alpha- beta- and gamma
The alpha and beta Interferons
are cytokines produced from infected cells.
They bind to specific receptors on adjacent cells and protect
them from infection by viruses.
They form part of the immediate protective host response to
invasion by viruses.
In addition to these direct antiviral effects, alpha and beta
interferon also enhance the expression of class I and class II
MHC molecules on the surface of infected cells, in this way,
enhancing the presentation of viral antigens to specific
immune cells.
Their presence can be demonstrated in body fluids during
the acute phase of virus infection
Recombinant alpha and beta interferons are now
available and have been used for the treatment of
Chronic hepatitis B and C virus infections.

However, side effects such as fever, malaise and

weight loss have limited the use.
gamma Interferon (immune
interferon)
is a cytokine secreted by TH1 CD4 cells.

Its function is to enhance specific T cell

mediated immune responses.
Mechanism of action of the
interferons :
1- Enhancement of the specific immune response.
By increasing the expression of MHC class I molecules on the
surface of infected cells, the interferons increase the opportunity
for specific cytotoxic T cells to recognize and kill infected cells.

2- Direct antiviral effect

a) degradation of viral mRNA
b) inhibition of protein synthesis
Prevents the infection of new cells
 3-Immunoglobulin Therapy

Passive Immunization
Passive immunization is the transfer of immunity to a host by
means of immunoglobulins (preformed antibodies).

These immunoglobulins are typically prepared by cold ethanol

fractionation as a 16% solution of gammaglobulin from large
pools of serum obtained from the blood donations of at least
1000 donors.
Immunoglobulin from immune individuals can be used as
prophylaxis to prevent viral infections in exposed, but non immune
individuals.

It works by binding to extra-cellular virions and preventing them

from attaching to and entering susceptible cells.

The protective effect is short lived (up to three months) because

the antibodies are metabolized by the host.
Normal" Immunoglobulin
This is a pooled product, prepared from the serum of normal blood
donors.

It contains low titers of antibody to a wide range of human viruses.

It is mainly used as prophylaxis against:

- hepatitis A virus infection,
- parvovirus infection, and
- enterovirus infections (in neonates).
- It may also be given as passive protection to HIV-infected babies
 Hyper-immuno globulin
Immunoglobulin may be prepared
from the serum of selected individuals
who have high titers of antibody to
particular viruses.
Examples include
- Zoster immuno globulin
Prevention of Varicella in immunocompromised children and
neonates.
Human Rabies immunoglobulin
Post-exposure prophylaxis in an individual who has been bitten
by a rabid animal.
Hepatitis B Immuno globulin
Non-immune individual who has been exposed to HBV.
RSV Immuno globulin
Treatment of respiratory syncitial virus infections in the very
young
 VACCINES
The introduction of vaccination has
been one of the most decisive advances
leading to the dramatic downward trend
in the incidence of many viral diseases
The principle of vaccination is to induce a "primed" state in the
vaccinated subject so that, following exposure to a pathogen, a
rapid secondary immune response is generated leading to the
accelerated elimination of the organism and protection from
clinical disease.

Success depends on the generation of memory T and B cells

and the presence in the serum of neutralizing antibody
 Attributes of a good vaccine
1.Ability to elicit the appropriate immune response for the particular pathogen:
Tuberculosis - cell mediated response most bacterial and viral infections - antibody
2. Long term protection
ideally life-long

3. Safety
vaccine itself should not cause disease

4. Stable
retain immunogenicity, despite adverse storage conditions prior to
administration

5. Inexpensive
 Types of Vaccine
Vaccines in general use include: LIVE vaccines; and KILLED vaccines
Also Subcellular fractions . Recombinant proteins and DNA VACCINES.

Vaccines are available for:

Hepatitis B virus
Hepatitis A virus
Influenza
Measles
Mumps
Polio
Rubella
Rabies
Yellow Fever
 a. Live Vaccines
1. Live attenuated organisms
Organisms whose virulence has been artificially reduced by in vitro
culture under adverse conditions, such as reduced temperature.
This results in the selection of mutants which replicate poorly in the
human host and are therefore of reduced virulence
Replication of the vaccine strain in the host reproduces many
of the features of wild type infection, without causing clinical
disease.

Potential drawbacks to these vaccines include:

the danger of reversion to virulence and
the possibility of causing extensive disease in
immunocompromised individuals .
 2. HETEROLOGOUS VACCINES

Closely related organism of lesser virulence, which

shares many antigens with the virulent organism.
The vaccine strain replicates in the host and induces
an immune response that cross reacts with antigens of
the virulent organism.
The most famous example of this type of vaccine is
vaccinia virus:
Both cowpox virus and vaccinia virus are closely related to
variola virus, the causative agent of smallpox.

The eighteenth century physician, Edward Jenner observed

that milkmaids who had been infected with cowpox virus
were immune to smallpox.

Widespread use of vaccinia virus as a vaccine has lead to the

world-wide eradication of smallpox
 3. Live recombinant vaccines
It is possible, using genetic engineering, to introduce a gene
coding for an immunogenic protein from one organism into the
genome of another (such as vaccinia virus).

The organism expressing a foreign gene is called a recombinant.

Following injection into the subject, the recombinant organism

will replicate and express sufficient amounts of the foreign protein
to induce a specific immune response to the protein
 Attributes - live vaccines
1.Ability to elicit the appropriate immune response for the
particular pathogen: Tuberculosis - cell mediated response most
bacterial and viral infections - antibody

. Good immune response

- Both Cell Mediated Immunity and antibody responses.
- Immunity is long lived
- Single dose
 Attributes - live vaccines
2. Long term protection
ideally life-long

3. Safety
vaccine itself should not cause disease. Safety.
Danger of reversion to virulence, or Severe disease in immunocomprised

4. Stable
retain immunogenicity, despite adverse storage conditions prior to
administration Organisms in the vaccine must remain viable in order to
infect and replicate in the host

5. Inexpensive Cheap to prepare

.
 b. Killed (inactivated) vaccines
When safe live vaccines are not available, either
because attenuated strains have not been
developed or else because reversion to wild type
occurs too readily, it may be possible to use an
inactivated preparation of the virulent organism
to immunize the host.
The organism is propagated in bulk, in vitro, and
inactivated with either beta-propiolactone or
formaldehyde.
These vaccines are not infectious and are therefore
relatively safe.
However, they are usually of lower immunogenicity and
multiple doses may be needed to induce immunity.
In addition, they are usually expensive to prepare.
 Attributes - Killed vaccines
Immune response poor; only antibody - no cell
immediated immune response.

Response is short-lived and multiple doses are needed.

May be enhanced by the incorporation of adjuvant into

the vaccine preparation
1. Safety
Inactivated, therefore cannot replicate in the host and cause disease.
Local reactions at the site of injection may occur.

2. Stability
Efficacy of the vaccine does not rely on the viability of the organisms.
These vaccines tend to be able to withstand more adverse storage
conditions.

3. Expense
Expensive to prepare.
 C.Subcellular fractions
When protective immunity is known to be
directed against only one or two proteins
of an organism, it may be possible to use a
purified preparation of these proteins as a
vaccine.
The organism is grown in bulk and inactivated, and then the protein
of interest is purified and concentrated from the culture suspension.

These vaccines are safe and fewer local reactions occur at the
injection site.

However, the same disadvantages of poor immunogenicity and the

need for multiple boosters applies
 D. Recombinant proteins
Immunogenic proteins of virulent organisms may be
synthesized artificially by introducing the gene
coding for the protein into an expression vector,
such as E-coli or yeasts.
The protein of interest can be extracted from
lysates of the expression vector, then
concentrated and purified for use as a vaccine.
The only example of such a vaccine, in current
use, is the hepatitis B vaccine.
 Adjuvants
Certain substances, when administered simultaneously with a
specific antigen, will enhance the immune response to that
antigen.

Such compounds are routinely included in inactivated or

purified antigen vaccines.
 Adjuvant in common use:

1. Aluminium salts
First safe and effective compound to be used in
human vaccines.
It promotes a good antibody response, but poor
cell mediated immunity.
Liposomes and Immunostimulating complexes .2
(ISCOMS)

Complete Freunds adjuvant is an emulsion of .3

Mycobacteria, oil and water
Too toxic for man
.Induces a good cell mediated immune response
4. Incomplete Freund's adjuvant as
above, but without Mycobacteria.

5. Muramyl di-peptide
Derived from Mycobacterial cell wall.

6. Cytokines
IL-2, IL-12 and Interferon-gamma.
POSSIBLE MODES OF ACTION:
By trapping antigen in the tissues, thus allowing
maximal exposure to dendritic cells and specific T and
B lymphocytes.

By activating antigen-presenting cells to secrete

cytokines that enhance the recruitment of antigen-
specific T and B cells to the site of inoculation.
F-DNA VACCINES

DNA vaccines are at present experimental,

but hold promise for future therapy since
they will evoke both humoral and cell-
mediated immunity, without the dangers
associated with live virus vaccines.
The gene for an antigenic determinant of a pathogenic
organism is inserted into a plasmid. This genetically
engineered plasmid comprises the DNA vaccine which
is then injected into the host. Within the host cells, the
foreign gene can be expressed (transcribed and
translated) from the plasmid DNA, and if sufficient
amounts of the foreign protein are produced, they will
elicit an immune response