vaccine development against malaria parasite and the efficacy stage specific vaccine.

1. Presented BY
SWARNENDU BASAK
DEPARTMENT OF ZOOLOGY
VISVA-BHARATI

2. General Introduction
 Malaria is one of the most important and tropical parasitic disease especially in
Africa.
 Causative agent- protozoan parasite Plasmodium sp.
 Four species of plasmodium, including P. falciparum (responsible for high mortality),
P. vivax , P. ovale, P. malariae.
 In the year 1973 pre-erythrocytic (sporozoite) vaccine develop from P.
falciparum, protection sustained for 7 months (species specific but not strain specific).
 Theree types of potential malaria vaccine, each attacking a different stage of their life
cycle, include pre-erythrocytic, blood stage vaccine, transmission blocking vaccine.
 RTS,S/AS02 has reached the stage of phaseIII clinical trials.

3. What is vaccine?
 A biological preparation or combination which is work as stimulating agent
and provides an active acquired immunity to a particular disease.
 Vaccine consists of some agent that resembles a disease-causing micro-
organism, weakened or killed form of microbe, its toxins or one of its surface
proteins.
 Vaccine is used for stimulation of immune system for future recognition of
these agents as a pathogen finally destroy it and keep a record of it .

4. Life cycle of Plasmodium sp.

5. SPOROZOITE
LIVER
STAGE
ASEXUAL
STAGE
SEXUAL
STAGE
ANOPHELES
MOSQUITO Vaccine Candidate
CSP, SSP2
CS, TRAP, EXP-
1, LSA-1 , LSA-
3
MSP-1, MSP-2,
MSP-3, AMA-1
Pfs-25,
Pvs-25
Malaria Vaccine Target

6. Pre erythrocytic vaccine
 Pre-erythrocytic vaccine strategies aim to generate an
antibody response able to neutralize sporozoites and
prevent them from invading the hepatocyte, as well as to
elicit a cell-mediated immuneresponse able to interfere
with the intra-hepatic multiplication cycle of the parasites.
 CD4+ and CD8+ cytotoxic T cells (CTL), NK T cells have
been implicated in such a control .
 CSP vaccine
 RTS,S/AS02A
 DNA vaccine and live recombinant vaccine.

7. RTS,S
This candidate vaccine was developed by Glaxo Smith Kline
(GSK) in collaboration with the Walter Reed Army
Institute of Research (WRAIR).
 Composition-
The C-terminus (amino acids 207–395) of the CSP from P.
falciparum fused to the hepatitis B surface antigen and
expressed in the form of virus-like particles (VLPs) in
Saccharomyces cerevisiae.
 Initial Phase I clinical trials of RTS,S formulated with GSK
AS02 adjuvant, showed protection against malaria
challenge in six out of seven volunteers.(trials in the
Gambia demonstrated )
 The RTS,S candidate vaccine has continued in partnership
with PATH MVI, at phase-III study efficacy of RTS,S/AS02
at preventing a first malaria attack in 1–4 years old children
was about 30% .

8. Other DNA and live recombinant vaccine
Based on CSP antigen include plasmid DNA vaccine
and live recombinant vaccines that use (MVA),(FPV),
Adenovirus, Sindbis virus, yellow fever virus or a cold-
adapted attenuated influenza virus strain as a vector.
vaccine was tested in a “proof-of-concept” Phase I
study carried out by the US Navy Malaria Program. The
vaccine elicited cell-mediated immune responses but
only modest antibody responses and no protection
against experimental challenge in human volunteers .

9. Multiple –antigen DNA vaccine
 Encode five different liver-stage antigens: CSP, liver
stage antigens 1 and 3 (LSA-1 and -3),
exported protein 1 (EXP1), and the sporozoite surface
protein 2(TRAP).
Induction of IFN-Ƴ secreting CD4+ and CD8+T-cell
responses .

10. ASEXUAL BLOOD STAGE VACCINE
 A number of parasite protein including MSP-1, MSP-2,
MSP-3, AMA-1, GLURP transiently accessible to
circulating antibodies and other responses.

11. MSP-1, MSP-2 AND RESA combination
o This vaccine combined the merozoite surface proteins
MSP-1 andMSP-2 with P. falciparum ring-stage infected-
erythrocyte surface antigen (RESA) in a Montanide
adjuvant formulation.
o A Phase I/IIb trial in 5–9 years old children in Papua
New Guinea showed a 62% reduction in parasite density.

12. AMA-1/MSP-1 chimera
 Developed by the Second Military Medical
University in Shanghai in partnership with the WHO
 A chimeric fusion of domain III ofAMA-1 and the 19-
kD portion of MSP-1 called P. falciparum chimeric
protein 2 (PfCP-2.9).
 efficiently block parasitic growth

13. GLURP VACCINE
 GLUP present on parasitophorous membrane of mature
schizont .
Induce ADCC pathway.

14. Transmission blocking vaccine
 induce antibodies against the sexual stage antigen.
Prevent the development of infectious sporozoite in
salivery gland of anopheles mosquito.
Protect communities from infection not individually.
Develop from P. falciparum ookinete surface antigens.
Pfs25

15.  After vaccination secondary immune response
After vaccination
secondary immune
response
Antigen
MP DC
APC cell
NK
CD-4 T
CELL
MHC II MHC I
CTL
INF-Ƴ
B
CELL
IgG-2a
IgG-3
Ag-Ab
mediated
killing
Production
of NOS
NO
KILL
CD-8 T
CELL
IL-4
B
CELL
IgG-1 , IgG-2h,
IgG-2
IL-
16
T CELL
REGULATOR OR
SUPPRESSOR
IL-10
TNF-α
IL-β
FAS
FADD
CASPASE
APOPTOSIS

16. after vaccination secondary
immune response of
erythrocytic pathway
same pathway
like pre-
erythrocytic
vaccine pathway
Antibody
produce IgG-
2a,
IgG-3, IgG-2,
IgG-2h
Ag-Ab
mediated
killing
Blocking interaction of
endothelial cell receptor CD-36
with CIDR region of EMP-1,
Antibody binds with CIDR
region cause cytoadhesion
blocking
NK CELL
.
Infected
RBC
FC
REGION
NK
CELL
FC RECEPTOR
ADDC

18. Conclusion
An ideal malaria vaccine should be safe, highly effective,
and provide long-term immunity, besides being stable,
easy to administer.
We hope in near future successful low expensive malaria
candidate vaccine can be developed which will
affordable in all endemic countries.

19. References
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Humoral immune responses in volunteers immunized with irradiated Plasmodium
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Protection of humans against malaria by immunization withradiation-attenuated
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20. Thank you