Antiviral chemotherapy

& viral vaccines

 Antiviral chemotherapy
• Because viruses are obligate intracellular parasites, antiviral agent must be;
1. Capable of selectively inhibiting viral infection without damaging the host cells.
2. Reduce disease symptoms without modifying the immune response in the host.
• Antiviral drugs are needed against viruses for which vaccines are not available or not
effective either due to genetic variability (Rhinoviruses) or highly changing virus
(influenza, HIV).
• Types of antiviral agents:
1. Nucleoside analogs: They inhibit nucleic acid replication by inhibition of enzymes of the
metabolic pathways for purines or pyrimidines or inhibition of polymerasees for
nucleic acid replication. Most of these agents are limited in inhibitory activity to use
against herpes viruses & HIV.
• e.g. Acyclovir ( Zovirax) (Herpes viruses).
• Valcyclovir effective in the treatment of herpes zoster.
• Ganciclovir : active against CMV.
• Didanosin (DDI): inhibit the HIV reverse trascriptase.
• Lamivudine: inhibit HIV reverse trascriptase. Also effective against HBV.
• Rabavirin: (HBV).
• Zidovudine ( Azidothymidine, AZT): blocking synthesis of proviral DNA of HIV.
 Antiviral chemotherapy
2.Nucleotide analogue:
• e.g. Cidofovir: active against CMV & HSV.
3. Reverse transcriptase inhibitors: (HIV).
4. Protease inhibitors: e.g. Indinavir, Ritonavir, Saquinavir.Inhibit HIV protease.
5. Other types of antiviral agents: e.g. Amantadine & Riantadine (Influenza A).
Neuraminidase inhibitors e.g. zanamivir (Relenza) & Oseltamivir (Tamiflu).
• Foscarnet: for the treatment of CMV retinitis & HSV.
• Interferons (INFs): are host-coded proteins that inhibit viral replication. INFs
modulates humoral & cellular immunity & have broad cell growth regulation
activities. There are three general groups; INF-α, INF-β & INF-γ .
• Synthesis of INFs: INFs are produced by all vertebrates. Normal cells are
synthesized INFs when they induced to do so. Viral infection is a potent
inducer .RNA viruses are stronger than DNA viruses. Different INFs are
produced by different cell types. INF- a & INF-B are produced by many cells,
while INF- γ produced mainly by lymphocytes.
 Antiviral chemotherapy

• Antiviral activity & other biological effects:

• INFs are first recognized by their ability to interfere with
viral infection. They produced soon (< 48 hrs) after viral infection
in the body before the appearance of the antibodies in the blood
(several days). This suggests that Ifs plays a primary role in the
defense of the most against viral infections.
• INFs as a cytokine also exhibit a wide variety of all regulatory
activities, including inhibition of cell growth, differentiation and
modulation of immune response ( increase expression of MHC
antigens, Enhanced NK cell activity). INFs are almost always host
species-specific in function ,but not virus specific.
Some antiviral drugs
 Viral vaccines

• The purpose of viral vaccines is to utilized immune response of the host to

prevent viral disease.
• Control by vaccination can be achieved by:
1. limiting the replication of virulent viruses upon subsequent exposure.
2. Preventing spread to target organs where the pathological damage occur.
3. Prevent the appearance of tumors (e.g.HBV vaccine prevent PHCC).
• Certain viral characteristics may hurdle the development of effective
vaccine:
1. Genetic variability (e.g.Rino, HCV)
2. Existence of large animal reservoirs (e.g. influenza).
3. Integration of viral DNA into host chromosomal DNA(e.g. Retroviruses).
4. Transmission by cell that not expressed viral Ags (e.g.HIV)
5. Infection of the cells of the immune system (e.g. HIV).
 Killed virus vaccines
a. Killed virus vaccines:
Killed or inactivating vaccines are made by purifying viral replication
& then inactivating viral infectivity.
• Advantage: there is no reversion to virulence by the vaccine
virus.
• Disadvantages:
1. Difficulties in manufacturing
2. Brief immunity, thus it needs booster doses
3. Inadequate local immunity, although the circulating Igs are high.
4.Poor Cell mediated immunity.
5.Hypersensitivity to subsequent vaccination.
 Attenuated live-virus vaccine

B. Attenuated live-virus vaccine:

Live virus vaccines utilize virus mutants that antigenically overlap with wild type
virus but are restricted in some steps in the pathogenesis of disease.
• Advantages:
1. Stimulate long-lasting antibody production.
2. Induce good cell mediated immunity.
3. Induce antibody production and resistance at the portal of entry.
• Disadvantage:
1. The risk of reversion to greater virulence
.Presence of accidental agents that latently infecting the culture substrate .2 •
3. The risk of persistent infection in vaccinees.
4. Limited shelf life of these vaccines.
5. Interferance by coinfection with a naturally occurring wild-type virus.
 Subunit & Genetically engineered vaccines

C. Subunit vaccines: Based on the separation of the most

immunogenic units of the microorganisms, e.g. malaria
vaccines & some other parasite vaccines.
It is totally safe & there are little or no adverse reactions.
D. Genetically engineered vaccines: based on mass production
of certain microbial proteins (immunogenic) through
genetically engineered the corresponding gene coding for that
protein (Hybridoma cell technology), It is totally safe & there
are no considerable disadvantages e.g. HBV vaccine, Influenza
vaccine
 Antisera (Hyperimmunoglobulins)

These are preparations of specific antibody (either monoclonal or polyclonal) that

confers protection when administered either before or shortly after exposure
to pathogen. These antibodies act by neutralization of viruses before they
being entered to the host cell, & thus prevent infection. These preparations
are made by one of the following procedures:
1. Derived from pooled plasma of cured or carrier individuals. Antibodies
prepared by this procedure are usually polyclonal. Although these
preparations are heat-heated, they still carry a possible risk of infection by
other pathogen present in the serum.
2. Hybridoma cell technology:
Hybridoma cell are prepared by hybridization of B lymphocytes (that have the
ability of antibody secretion) with the myloma cells (these are certain
cancerous cells that have the property of long-living). Hybridization of these
cells yield a hybrid cells that have the both properties of antibody secretion
and long-living. Antibodies produced by this technique are usually monoclonal
& highly specific in action.
 Antisera (Hyperimmunoglobulins)

• Advantages of antisera:
1. It induces high levels of antibody in the serum within a short
time after administration, & thus confers a rapid protection
against infection.
2. It can be given before exposure to pathogen as prophylaxis.
3. It can be given shortly after exposure to pathogen.
• Disadvantages:
1. Risk of infection by persistent or latent pathogens.
2. Short duration of protection (usually 2-3 months).
3. Hypersensitivity upon subsequent injection.
e.g. HB IG, rabies virus IG