No commercially available malaria vaccine at the present time.
RTS,S/AS01 is the most advanced vaccine candidate against malaria.
Commonest infectious disease in the tropics
200 millions per year affected with malaria
3 millions per year die due to malaria
3. Overview
Requirement of a Malaria
Vaccine
Vaccine Development Is
Elusive
To Combat Malaria
Why a Multi-invention
Approach?
An Ideal Vaccine Would..
Challenges in Research on
Malaria Vaccine
Malaria Life Cycle
Immunity In Malaria
Immunological Boosting
Immune Response
Malaria Vaccine Approaches
4. Requirement of a Malaria Vaccine
Commonest infectious disease in the tropics
• 200 millions per year affected with malaria
• 3 millions per year die due to malaria
Increased mortality and morbidity related to malaria
A vaccine would be a safe and effective way to control the disease
5. Vaccine Development Is Elusive
• Complex life cycle of the malaria
parasite
• In the human
• In the vector
• Allelic diversity
• Antigenic variations
Reasons
7. Why a Multi-invention Approach?
Increased resistance of the parasite to anti-
malarial drugs
Increased resistance of the vector mosquito to
insecticides
8. An Ideal Vaccine Would..
Prevent the
infection at first
instance
Decrease the
intensity of
infection
Prevent malaria
transmission
9. Challenges in Research on Malaria Vaccine
Difficulty in
growing the
parasite in large
quantities
Difficulty in
evaluation
Parasite escaping
the host immune
response
Complexity of
conducting clinical
trails and field trials
Mutations of the
parasite
Antigenic variations
• MSA-I has 8 variants
• MSA-II has 10 variants
Multiple antigens
specific to species
and stage
12. • ADCC
• Boosting
possible
• Transfer of Ab
to mosquito
• Boosting
limited
• Cell mediated
immunity
• Boosting
possible
• Neutralizing
Abs
• Boosting
limitd
Intra-vascular
SPOROZOITES
Intra-
hepatocytic
LIVER STAGE
Intra-
erythrocytic
BLOOD STAGE
MEROZOITES
Intra-
mosquito
SEXUAL
STAGES
13. Immunological Boosting
Sporozoites are
free swimming
• Hence antibodies can
target sporozoites
1 sporozoite gives
rise to ~40,000
merozoites
• So must be neutralized
Antibody level
should be very high
to achieve long
lasting protection
So, immunologic
boosting via natural
infection is limited
18. 1. Liver stage
Cell mediated immunity
T cells (CD4+, CD8+) involve
Destroy infected liver cells
Boosting is possible
19. 2. Blood stage
Antigen dependent cell
mediated cytotoxity (ADCC)
Destroy infected RBCs
Boosting with natural infection
is possible
20. 3. Sexual stage
Depends on transfer of the host’s antibody
into mosquito during a blood meal
Rely on very high antibody titres
Limited boosting with natural infection
23. Pre Erythrocytic Vaccine
Aims
• Protect against the early stage of infection
• Prevent infection/ liver cell infection
• Host would suffer no malaria disease
• For travellers travelling to endemic areas
24. Blood Stage Vaccine
Blood stage
• Most destructive stage
• Rapid replication in RBC
Does not aim to block all infection
Aims
• Reduce parasitic load in blood
• Reduce severity of the disease
For children and adults living in endemic areas
25. Transmission Blocking Vaccine
Antibodies prevent the parasite maturing in the vector
Not preventing a person getting malaria
Not reducing symptoms of the disease
For communities ‘at-risk’ of malaria
26.
27. RTS,S /AS01 Vaccine
• The world’s first malaria vaccine that has been shown to provide
partial protection against malaria in young children.
• Acts against Plasmodium falciparum
• The phase III trial, conducted over 5 years (from 2009 to 2014),
enrolled approximately 15 000 young children and infants in 7 sub-
saharan african countries
• Phase III trial was successful
• Children who received 4 doses of the vaccine had a significantly
lower risk of developing malaria, including severe malaria
• Vaccinations are due to begin in 2018.