veterinary microbiology ppt veterinary viral vaccines and chemotherapy , masters of veterinary science

1. Viral Vaccines and Chemotherapy
Dr. Parminder Dalal

2. • A vaccine is a biological preparation
that provides active acquired
immunity to a particular infectious
or malignant disease.
• Vaccine typically contains an agent
that resembles a disease-causing
microorganism and is often made
from weakened or killed forms of
the microbe, its toxins, or one of its
surface proteins.
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3. History
• The early history of veterinary vaccines can be divided
into four stages.
• First stage - discovery of variolation against human
smallpox and its eventual evolution into vaccination.
• Second stage - discoveries of Louis Pasteur - early
production of numerous effective vaccines against
predominantly bacterial diseases.
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• Third stage- development of the canine distemper
vaccines, was a process of progressive improvement of
these vaccines and resulted from a growing knowledge
about viruses and their behavior.
• Finally, the sophisticated use of vaccines has led to
the elimination of two major diseases, smallpox and
rinderpest, and the near eradication of others.

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5. Golden age – growth of viruses in cell culture - 1950
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6. Variolation
&
Vaccination
• Greek people around 400 B.C. had learnt the primitive concept
of immunity from the observations that the plague survivors
did not suffer from plague second time in their life. Chinese
introduced the practice of ‘variolation’ (‘variola’ means
smallpox) around 1000 A.D. to prevent dreadful consequences
of the disease.
The Jennerian Era: (From vaccination to the birth of
Vaccinology: 1798 A.D.-1880 A.D.)
• Edward Jenner’s demonstration of the protective power of the
cowpox material against smallpox in humans in 1798 A.D.
marked the beginning of a new practice that was to lead
ultimately to total eradication of the disease.
• The practice was later named as vaccination (from Latin
‘vacca’ means cow) by Louis Pasteur in 1880 in honour of
Jenner’s use of pox material from cows to protect against
smallpox.
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The Pasteurian Era: (From vaccinology & immunology to beginning of
immunochemistry: 1880 A.D.-1910 A.D.)
• Pasteur discovered fortuitously attenuation of fowl cholera micro-
organisms, due to prolonged incubation of the growth in his
laboratory.
• Later, he attenuated other infectious agents by incubation at
elevated temperature (e.g. anthrax in 1880), dessication (rabies,
1885) and passage in unnatural hosts.
The first vaccinologist’ had thus been born who started applying
systematic scientific knowledge for the production of vaccines.
Pasteur expanded singular instance of Jenner’s vaccination into a
general concept of ‘prophylactic immunization’.

8. Contagious
Bovinepleuropneumonia
• This disease was a major problem in Europe
through the nineteenth century and inoculation
was first attempted in England and Germany at
that time.
• credit is usually given to Louis Willems of Hasselt
in Belgium, who in the early 1850s inoculated
lung fluid from affected animals into the tail of
recipient cattle. He used a large lancet dipped in
the fluid and used this to make two to three
incisions at the tip of the tail.
• It caused large abscesses, the animals sickened
and recovered, the tail commonly fell off but the
animals became immune.
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9. Types of vaccines
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Whole
pathogen
vaccine: Live
& Inactivated
Subunit
vaccines:
Toxoids, Protein
antigens etc.
administered with
adjuvants or through
virus- like particles
(VLPs) or through
bacterial “ghosts,”
Vectored
vaccines:
Bacteria &
Viral vectors
Nucleic acid
vaccines: RNA
& DNA, DNA
plasmid
vaccines.

10. Major groups of vaccines
• Modified-live (attenuated): a vaccine that contains an intact but
weakened pathogen which stimulates an immune response but does
not cause clinical disease.
• Inactivated (killed): a vaccine that contains a completely inactivated
pathogen, which is no longer infectious. These vaccines often contain
an adjuvant, which is a compound added to help improve the
protective immune response.
• Recombinant: a vaccine that is produced using genetic engineering
technology and using specific genetic material from a pathogen to
produce proteins which will stimulate an immune response when the
animal is vaccinated.
• Toxoid: a vaccine that is based on inactivated toxins produced by
pathogens. These vaccines stimulate immunity and protect the animal
against these toxins.
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11. USDA Categories of Modern Vaccine
USDA Categories of
genetically engineered
Veterinary Biologics
Description
I
Antigens Generated by
Gene Cloning
contain inactivated recombinant organisms or purified
antigens derived from recombinant organism
II
Genetically Attenuated
Organisms
containing live organisms that contain gene deletion or
heterologous marker gene
III
Live Recombinant
Organisms
Containing live expression vectors expressing heterolologous
genes for immunizing antigen or other stimulants
IV
Polynucleotide Vaccines
Polynucleotide vaccines
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12. Bovines viral vaccines
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13. Fmd Vaccine
• Indian Immunological
• Raksha - Ovac Trivalent (FMD Oil Adjuvant vaccine) contains tissue
culture virus strains, O, A, Asia-1, and inactivated with Aziridine
compound. Mineral oil is added as an adjuvant
• Cattle, Buffaloes, Calves and Pigs : 2 ml and Sheep and Goats : 1 m
in the mid-neck region, deep i/m
• Primary vaccination : 4 months of age (Cattle, Buffaloes, Sheep and
Goats).
• Primary vaccination : 2 months of age (Pigs).
• Booster : 9 months after primary vaccination
(Cattle/buffaloes/Sheep and Goats).
• Revaccination : Every 12 months thereafter (Cattle, Buffaloes, Sheep
and Goats).
• Revaccination : Every 6 months thereafter (Pigs).
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14. Vaccination of dairy animals
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15. Sheep and Goat
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Sr.
No.
Name of disease Type of vaccine Dose Age at first
dose
Booster Revaccination
1 FMD Polyvalent FMD 1 ml S/C or
I/M
3-4 months - Biannual
2 PPR Live virus 1 ml S/C 4 months - Annual
3 Goat & Sheep Pox Live attenuated 1 ml S/C 3-4 months After
1month
Annual

16. Sheep and goat
pox
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PPR
• live and inactivated vaccines
• The vaccination is done every year in healthy
sheep of above 3 months of age.
Sheep pox vaccines ( Live)
• Romanian strain is grown on primary lamb
testicle cell
• Ranipet strain is grown on primary lamb testicle
cell culture. (50th passage)
• Srinagar strain is vero cell adapted.
Goat pox vaccine ( Live).
• Uttarkashi strain (Vero cell adapted)
• Live, Sungri/96 strain.
• Live (Vero cell adapted) vaccine
strains of PPR-
• PPR Sungri 96 (India, lineage IV, Goat
origin)
• Arasur 87 (India,lineage IV, Sheep
origin)
• Coimbatore 97(India, lineage IV, Goat
origin).
• Nigerian 75/1.
• Dialo

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18. Dog vaccine
DHPPi : Modified Live Vaccine
L : Killed
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19. Vaccination of
cat
• For immunization of cats against
feline calcivirus, feline rhinotracheitis
virus & feline panleucopenia virus.
• Live attenuated vaccine.
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FELINE TRICAT VACCINE
Vaccine Age at
vaccination
Booster Revaccination
Feline Tricat
vaccine
8-9 weeks 12 weeks Annual
Rabies 3 months After 1 month Annual

20. Vaccines for horses
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22. Swine
Swine fever
Highly immunogenic attenuated strain of Swine
Fever Virus propagated in tissue culture, stabilised
in a freeze dried
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23. Broilers
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Sr.
No.
Name of
disease
Type of
vaccine
Dose Age at
first dose
Booster
1 Ranikhet
disease
( Newcastle
disease)
Strain F or BI
or La Sota
0.5 ml I/N
or I/O or
S/C or
D/W
1-7 days R2B strain
6-8 weeks
16 weeks
2 Infectious
bronchitis
La
Massachusett
us strain
I/O 3-4 weeks 14-16
weeks
3 Infectious
bursal
disease
Live
attenuated
I/O or D/W 18-21 days 25-28 days
4 Marek’s
disease
HVT 0.2 ml S/C 1-3 days -

24. Layers
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Sr.
No.
Name of
disease
Type of
vaccine
Dose Age at
first dose
Booster
1 Marek’s
disease
I/M 1 day
2 Ranikhet
disease
La Sota I/M 1 day
Mesogenic
strain
Spray
occulonasal
drops
1-7 days
Lentogenic
strain ( La
Sota)
Spray , D/W,
I/M
3-4 weeks
Killed
vaccine/mesoge
nic strain
D/W 8 weeks
R2B strain O.5 ml I/M,
D/W
16-18
weeks
40th
week
3 Fowl pox Cell culture
vaccine
0.2 ml wing
web or I/M
6-8 weeks 18-20
week

25. Chemotherapy
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26. The therapeutic use of chemical
agents to treat disease
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Father of antiviral
chemotherapy - William H.
Prusoff
• The first antiviral drugs were
introduced in the 1960s.
• Viruses replicate within host cells,
using host cell machinery, therefore
there were fewer targets for
chemotherapy against viruses.
 Antibiotics
• It help to treat bacterial infections
• Mostly bacteria found outside of cells, it is
easier for drug to target
• antibiotics clearly distinct from their
counterparts or against bacteria cell wall
 Antivirals
• It only works against specific virus
• It replicates within host, fewer obvious targets
for chemotherapy against viruses
• Viruses share common feature with host cell

27. Targets of
antiviral drugs
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Figure: Inhibitors at different stages in replication cycle

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29. Pleconaril
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• Capsid binding drug act by direct
binding to virions
• Binding of the drug to the pocket
displaces the bound lipid molecule and
drug alter the structure of canyon floor
• Interferes with attachment of virion to
receptor and entry of viral genome
into the cytoplasm
1)

30. Enfuvirtide
30
Maraviroc
• Binds to HIV-1 virions and prevent virus entry
was approved by the FDA in 2003
• This drug blocks a conformational change in the
viral envelope protein gp41, which is required
for fusion btw the viral envelope and the cell
membrane
• Maraviroc, blocks attachment and entry
by binding to cellular receptor for HIV-1
• It is a highly unusual antiviral drug
because it targets a host protein-CCR5
rather than viral protein

31. Amantadine block ion channels and
inhibits uncoating of influenza virions
Uncoating
31
• Influenza virions in endosomes
undergo fusion with the
endosomal membrane upon drop
in pH induced by proton pump,
Amantadine blocks the M2
channel
2)

32. Nucleoside
analogues target
viral DNA
polymerases
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a) Acyclovir is selectively
phosphorylated by herpesvirus
thymidine kinases
• Many antiviral drugs target genome replication than
any other stage of virion infection
• Useful antiviral drugs are nucleoside analogues are
three: acyclovir and ganciclovir both active against
herpesviruses and Azidothymidine(AZT) active
against HIV-1
• Acyclovir used to treat herpes simplex
virus infection or varicella zoster virus
• Acyclovir is converted to the
monophosphate by the viral enzyme
and then converted to acyclovir
diphosphate and triphosphate by
cellular kinase
• Acyclovir triphosphate is an inhibitor of
herpesvirus DNA polymerases more
potently than cellular DNA
polymerases by mechanism termed
“induced substrate inhibition”
3)

33. Ganciclovir
• Ganciclovir used against human
cytomegalovirus
• Ganciclovir must be phosphorylated
to act as an inhibitor of DNA
polymerase
AZT
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• Azidothymidine (AZT; zidovudine) was
the first drug approved for treatment
of AIDS
• Activation of this drug is not selective;
it occurs in uninfected or infected cells
unlike ACV & GCV
• AZT monophosphate converted to AZT
diphosphate by cellular thymidine
kinase and triphosphate by nucleoside
diphosphate kinase
• Triphosphate is potent inhibitor of HIV
reverse transcriptase

34. Non-nucleoside
inhibitor selectively
target viral
replication enzymes Nevirapine, a non-nucleoside inhibitor
of HIV-1 reverse transcriptase
• bind to reverse transcriptase at a
site close to the active site for DNA
polymerase activity, and they
drastically slow the rate of DNA
polymerization
• Selective in nature
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35. Protease inhibitors
can interfere with
virus assembly and
maturation HIV-1 infected cells treated with protease
inhibitors continue to make viral proteins, but
the Gag polyprotein is not cleaved
Therefore, virus particles bud from the infected
cells, but they are immature and do not
successfully infect other cell
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Ritonavir: a successful
protease inhibitor of HIV-1
4)

36. Neuraminidase inhibitors
inhibit release and spread
of influenza virus
Zanamivir, Peramvir And
Oseltamivir
Neuraminidase inhibitors drugs are used for
blocking the enzyme neuraminidase to prevent
the influenza infection from spreading
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5)

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38. Limitation of
antiviral drugs
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Limitations include a narrow
antiviral spectrum
Ineffectiveness against the latent
virus
Development of drug-resistant
mutants and toxic side effects

39. REFERENCES
• Fundamentals of Molecular Virology by NICHOLAS H. ACHESON
• Fenner’s Veterinary Virology
• History and progress of antiviral drugs: From acyclovir to direct-
acting antiviral agents (DAAs) for Hepatitis C
www.elsevier.es/rmuanl
• http://pubs.acs.org/journal/acscii
• https://veteriankey.com/a-brief-history-of-veterinary-vaccines/
• Brun A. (2016). Vaccines and Vaccination for Veterinary Viral Diseases:
A General Overview. Methods in molecular biology (Clifton, N.J.), 1349,
1–24. https://doi.org/10.1007/978-1-4939-3008-1_1
• Quality assurance and quality control, Part IV, Vaccine Manual
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40. THANK YOU!
Dr. Parminder Dalal
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