Humanpapiloma Virus Vaccine. The presentation contains information about the 2 HPV Vaccines GARDASIL and CERVARIX

1. HUMAN PAPILLOMA VIRUS VACCINE
FREYA CARDOZPRESENTED BY: FREYA CARDOZO

2. FAMILY Papillomaviridae
TYPE Non enveloped
GENOME dsDNA
CAPSID Icosahedral
GENES Early genes (E1, E2,
E4, E5, E6 and E7)
regulate viral
transcription and
genome replication
Late genes (L1 and
L2), which are
involved in the viral
capsid structure.
PRESENTED BY: FREYA CARDOZO

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4. L1 is the major capsid protein, and it forms the capsid by self-assembly of
72 pentamers.The other capsid protein, L2 that is present in different
ratios. PRESENTED BY: FREYA CARDOZO

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7. HPV
EPISOMAL
In basal cells, the viral early genes are
expressed and the genome is replicated
as anepisomeat approximately 10^2
copies/cell
Late gene expression
E4 protein and capsid gene expression
andvirionformation.
INTEGRATIVE
Disruption of E2
Loss of late gene expression(L1,L2)
expression of E6 and E7
E6-compromises TP53
E7 inactivates retinoblastoma
PRESENTED BY: FREYA CARDOZO

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10. VLPs are an attractive vaccine strategy:
 No viral genetic material
 Production in non mammalian expression
systems
 High-density B-cell epitope display
 Intracellular presentation of T-cell epitopes
that induce potent humoral and cellular
immune responses, respectively.
PRESENTED BY: FREYA CARDOZO

11.  Four antigen 6,11,16,18 L1 proteins
16,18:hrHPV
6,11:Angiogenital warts
 Produced By Merck and approved by FDA in 2006
 Saccharomyces cerevisiae expression system used
 pGAL110 contains GAL1-GAL10 promoter, yeast ADH1 terminator
(ADH1) for transcription termination and poly(A).
 Production
L1 gene of 4 strains
isolated
L1 genes cloned in
pGAL110
Used to transform
recombinantS.cerevisiae Induce bygalactose
PRESENTED BY: FREYA CARDOZO

12. FORMULATION
It contains 20ug of HPV type 6L1 protein, 40ug of HPV type 11L1
protein, 40ug of HPV type 16L1 protein, 20ug of HPV type 18L1 protein
and 225ug of aluninium hydroxyphosphate sulfate
PRESENTED BY: FREYA CARDOZO

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14.  Contains HPV types 16 and 18
 Produced by Merck and approved by FDA
in 2009
 Baculovirus expression vector used
 Prdoduction L1 genes of HPV 16,18
strain isolated
Clone inbaculovirus
InfectTrichoplusianicells
Incubate in serum free
media for 2days
Harvest
Centifugation
Extraction with buffer
Clarification:Tangentialflow
filtration
Ion exchange
chromatography
PRESENTED BY: FREYA CARDOZO

15. TLR4 SIGNALLING PATHWAY
 MPL is 3-O-desacyl-4-
monophosphoryl lipid A derived
from Salmonella Minnesota
R595.
 LPS activates innate immunity
via TLR-4
 MPL agonist to TLR-4
 LPS is recognized by LBP
followed by CD14.This
associated the TLR and MD2
 Complex formation > production
of proinflammatory cytokines by
MyD88 pathway
 LPS also mediates IFN inducible
genes by MyD88 independent
pathway
AS04 ADJUVANT SYSTEM
PRESENTED BY: FREYA CARDOZO

16. MPL(TLR4 agonist)
Virus like particles(L1 of 6,11,16,18)
Role of AS04 adjuvant system in
Bivalent HPV vaccine
PRESENTED BY: FREYA CARDOZO

17. CONTENT QUADRIVALENT
VACCINE
BIVALENT
VACCINE
Generic Name GARDASIL® CERVARIX®
Produced by Merck&Co.Inc. GSK
HPV types 16,18:hrHPV
6,11:Angiogenital warts
16,18:hrHPV
Produced and
expressed in
Saccharomyces cerevisiae
expression system.
pGAl110 expression
vector
Trichoplusia insect cell line
infected with L1
recombinant baculovirus
Adjuvant Aluminium
Hydroxyphosphate sulfate
AS04
Approved by
FDA in
2006 2009
Dosage 0.5-mL dose at the
following schedule: 0, 2
months, 6 months
0.5-mL dose at the following
schedule: 0, 1, and 6
months
PRESENTED BY: FREYA CARDOZO

18. Proportion of responders for (A) HPV-16- and (B) HPV-18-specific B-cell responses at Months 7, 12, 18 and 24. Black bars, Human
Papillomavirus Bivalent(Types 16 and 18) Vaccine (Recombinant, adjuvanted, adsorbed)(CervarixR); white bars, Human
Papillomavirus Quadrivalent (Types 6,11, 16 and 18) Vaccine, Recombinant (GardasilR). Responders defined as
subjects with detectable HPV type-specific memory B-cells [>1 cell/millioncells].
PRESENTED BY: FREYA CARDOZO

19. Geometric means ratios for (A) HPV-16- and (B)
HPV-18-specific CD4+ T-cell response at Months 7, 12, 18 and 24 (Solid
black lines)Bivalent (Types 16 and 18) Vaccine -solid gray lines, Human
Papillomavirus Quadrivalent(Types 6, 11, 16 and 18) Vaccine,
Recombinant (GardasilR
PRESENTED BY: FREYA CARDOZO

20. Quadrivalent HPV Bivalent HPV
 A study of qHPV vaccine
for women aged 9-26
from 2006-2008
 Ratio of Adverse effects
onset 53.9/100000
 Syncope,Headache,local
site
reactions,urticaria,nause
a,hypersensitivity
 GBS,autoimmune
disorder,anaphylaxis
 A study of bHPV vaccine for
women aged 9-26 from 2009-
2011
 Ratio of Adverse effects
onset 11.6/10,0000
 Fever,local
reaction,erythema,headache
,malaise
 Migraine,Bell's
palsy,anaphylaxis,GBS,severe
anemia,viral meningitis
PRESENTED BY: FREYA CARDOZO

21.  Innovax YST Biotech.Co.Ltd.(China)-2003
Using Escherichia coli expression system to produce HPV type
16 & 18 antigens.
In clinical trial phase III
 Takeda Ltd(Japan)-2010
Vaccine that has neutralizing activity against SIX HPV types.
In pre-clinical stage trials
 Eyegene Inc(Korea)
Using yeast expression system to produce HPV type 16 & 18 antigens
Uses CIA05 adjuvant system(LPS of E.coli)
Induces Th1,Th2 and Th17
In clinical trial phase I
 Merck.Co.Ltd-GARDSIL-9
Nonavalent Vaccine against HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58
Approved
PRESENTED BY: FREYA CARDOZO

22. LIMITATION IMPACT ALTERNATIVES
Cost of manufacturing,
trials and intellectual
property leads to high
vaccine price
Developing countries
cannot afford the
vaccine thus continue
to bear the burden of
cervical cancer
L1-VLP vaccines in
cheaper production
systems such as plants or
bacteria or reduce
number of doses or
combine with childhood
vaccines
Type restriction Does not protect
against all HPV types
causing cervical cancer,
thus screening must
continue for HPV-
vaccinated women
Add more high-risk HPV
VLP types to create a
highly
multivalent HPV VLP
A broadly protective
antigen
No therapeutic value No effect on individuals
with pre-existing HPV
infection
Alternative vaccine
constructs displaying E6
and E7
CONCLUDING REMARKS
PRESENTED BY: FREYA CARDOZO

23. TO TAKE OR NOT TO TAKE
THAT IS THE QUESTION!!!
THANKYOU!PRESENTED BY: FREYA CARDOZO

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 McKeage K, Romanowski B. AS04-adjuvanted human papillomavirus (HPV) types 16 and 18 vaccine
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PRESENTED BY: FREYA CARDOZO