1) Malaria vaccines aim to prevent infection, decrease disease severity, and reduce transmission. However, developing an effective malaria vaccine is challenging due to the parasite's high mutation rate and ability to evade the immune system. 2) Most research focuses on P. falciparum since it causes the most mortality. Potential vaccine candidates target different stages of the parasite's life cycle and include antigens like CSP, AMA1, MSP1, and Pfs25. 3) SPf66 was the first malaria vaccine tested in humans but showed limited efficacy. RTS,S is the most advanced candidate vaccine and has demonstrated up to 50% efficacy in clinical trials. However, more research is still needed to develop

1. R.Sathish Kumar
Altheanz ‘09
© RSK

2.  prevent the infection at the first instance
and if this is not possible, should decrease
the intensity of infection and should be
successful in preventing malaria
transmission.
 Reduce the clinical disease severity
 Reduce the transmission

3. Due to
 Multiple drug resistance of the parasitic
species plasmodium due to a very high rate of
replication
 Insecticide resistant female anopheles
mosquito.
Moreover the task of developing a preventative
vaccine for malaria is a complex process.
Majority of research into malarial vaccine are
focused on P.falciparum strain due to high
mortality rate caused by them.

6. Stage of
plasmodium
Antigens
Pre-erythrocytic Irradiated sporozoites , Circum Sporozoite Protein (CSP) or
peptides, Liver stage Antigens -1 (LSA-1)
Merozoite and
Erythrocytes
Erythrocyte Binding Antigen (EBA-175), Merozoite Surface
Antigen 1&2 (MSA-1&2) ; Ring Infected Erythrocyte Surface
Antigen (RESA); Serine Repeat Antigen (SERA); Rhoptry
Associated Protein (RAP); Histidine Rich Protein (HRP); Apical
Membrane Antigen-1 (AMA-1)
Gametocytes &
gametes
Pfs 25, 48/45k, Pfs 230
Combined vaccine
(cocktail)
SPf 66 (based on pre-erythrocytic and asexual blood stage
proteins of Pf)

7. Source- WHO

8.  The use of whole parasite either live or
attenuated as a vaccine is not recommended
because it is not feasible.
 So subunit vaccines are preferred ,isolated and
tested for Immunogenicity. The subunits may be
A. surface antigens
B. parasitic protein
C. recombinant protein derived from the
parasite
D. combined antigens

9.  The first vaccine developed that has undergone field trials
 Developed by Manuel Elkin Patarroyo in 1987.
 It presents a combination of antigens from the sporozoite
(using CS repeats) and merozoite parasites.
 During phase I trials a 75% efficacy rate was demonstrated
and the vaccine appeared to be well tolerated by subjects
and immunogenic.
 The phase IIb and III trials were less promising, with the
efficacy falling to between 38.8% and 60.2%.
 Despite the relatively long trial periods and the number of
studies carried out, it is still not known how the SPf66
vaccine confers immunity; it therefore remains an
unlikely solution to malaria

10.  Based on the circumsporoziote protein, but additionally has
the recombinant protein covalently bound to a purified
Pseudomonas aeruginosa toxin (A9).
 It is the most dominant surface antigen of the initial pre-
erythrocytic phase.
 A complete lack of protective immunity was demonstrated
in those inoculated at early stage.
LIMITATIONS
 Low efficacy , low immunogenicity.

11.  Blocks transmission of the parasite from vertebrate host to
mosquitoes.
 Genes encoding seven Pf antigens derived from the
 sporozoite (CSP and sporozoite surface protein 2),
 Liver (liver stage antigen 1),
 blood (merozoite surface protein 1, serine repeat antigen, and
apical membrane antigen 1),
 sexual (25-kDa sexual-stage antigen)
inserted into a single NYVAC genome to generate NYVAC-Pf7.
 safe and well tolerated.
o Specific antibody responses against four [out of 7] of the P.
falciparum antigens were characterized during 1a clinical trial.

12.  Vaccine consists of
- schizont export protein (5.1)
- 19 repeats of sporozoite surface
protein (NANP)
 Out of 194 children vaccinated in trials none
developed symptomatic malaria.
LIMITATIONS
 has low levels of immunogenicity
 Doesn’t contain any immuno dominant T-cell
epitopes.

13.  Most recently developed recombinant DNA
vaccine
 The RTS,S attempted by fusing the protein CPS
with a surface antigen from Hepatitis B, hence
creating a more potent and immunogenic
vaccine. When tested in trials an emulsion of oil
in water and the added adjuvants of
monophosphoryl A the vaccine gave 7 out of 8
volunteers challenged with P. falciparum
protective immunity

14.  Recent RTS,S Phase 2 trials (3 repeated
doses administered in 6 months leading up
to period of highest malarial transmission).
on Children ages 1-4 in Mozambique
 reduced clinical malaria episodes by 35%
with vaccine efficacy of approximately 71%
during first two months falling to zero% in
last 6 weeks

15. Efficacy = 41% source- AMANET
0 5 10 15 20 25 30 35 40
proportionofnotparasitemic
Daysaftervaccination
EfficacydataforRTS,S onetwo and threedoses
control
RTS,S

16.  Increased rate of malarial transmission
during final follow up period.
 Decrease in prroduction given by the last
vaccine booster.
 Polymorphism and clonal variation in
antigens of plasmodium
 Parasite induced immuno-suppression
 Intracellular parasites

17.  Difficulty of evaluation
 Parasites’ ingenious ways of avoiding hosts’
immune response
 Complexity of conducting clinical and field
trials
 Mutation of the parasites
 Antigenic variations e.g. CSP has 6 variants
 Multiple antigens, specific to species and
stage

18.  MVI is working with the International Centre for
Genetic Engineering and Biotechnology
(ICGEB) in New Delhi, India, to develop a vaccine
against malaria.This development effort includes
Bharat Biotech International Ltd. (Hyderabad),
which will manufacture the vaccine for preclinical
testing followed by initial safety trials in adults.