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• . These are dumped into the bloodstream when the infected cells lyse, stimulating
macrophages
• cytokines and other soluble factors which act to produce fever and rigors or even
death (CDC, 2019).
• Thus a vaccine at this stage is aimed at inhibiting erythrocyte invasion and reducing
symptoms. Because completely blocking merozoites replication is almost imposible.
Antigens explored in production of blood stage malaria vaccine
•merozoite surface proteins,
tethered with
glycophosphatidylinositol
(GPI)-anchored proteins,
integral membrane proteins or
as peripherally-associated
proteins
contained within
organelles known merozoites
as rhoptries and
• Erythrocyte bind
protein- EBA
175
• Merozoite P f E M P – 1,
surface antigen Pf332,
1 and (Beeson
et al., 2016). Rosettin,
• Ring infected erythrocyte
RAP and AMAI
surface antigen-RESA;
prevents further invasion
of already infected cell
and protects against
thermal damage Pei et
al., 2007)
Mechanism of action of blood stage vaccine
Inhibition of
merozoites invasion
into erythrocytes
through glycoprotein
A e.g EBA-175.
Inhibition of
merozoites invasion
into erythrocytes
Inhibit merozoites through band A anion
interaction with exchanger of RBCs)
RBCs e.g. AMAI e.g MSP 1
Current blood stage vaccine development
Location of protein Vaccine Efficacy tested progress
candidate
glycophosphatidylinositol (GPI)- MSPI(42- Ellis et al in 2010 recorded a 49 fold increase in antibody titre Phase1
anchored proteins C1/ALHYDROGE 2weeks after inoculation of 30 malari-naïve adults. Thus
L) optimal Ab respone but protection and durability not
guaranteed
MSP2 (McCarthy et al.2011) : induction of Ab reponse that mediated Phase
ADCI. problems with reactogenity with variable adjuvants thus I/IIb
require further refinement
Peripheral surface proteins MSP3 Complexex Reduction in incidence upon immunization with MSP3 as Phase 1
With MSP1 compared to control group. Short term protection against
clinical malaria (Cousens and Druilhe)
PfRH5 Induced Abs and conferred protection against a virulent Phase 1
heterologous Pf challenge. In vivi testing revealed expression
of 10different Pf Ags with ability to induce IgG Abs that were
able to recognize naïve malaria parasite assessed by IFA
Microneme proteins released onto AMAI- 54% increase in IgG Absfrom volunteers showed reactivity Phase 1
merozoites surface C/alhydrogel. with schizonts of Pf (malkin et al., 2005)
Combine with
protein base gene
FVO and 3D7
AMAI-RON2 In vivo mice model revealed induction Ab mediated complete Preclinical
infection against lethal P. yoelli. If successful in animals, this phase
will be a solution to overcome antigenic polymorphism.
(srinivasan et al., 2014)
Challenges face in the development of blood stage malaria vaccine
Antigenic polymorphism
of both merozoites as well as
infected erythrocyte surface
proteins.