9 Malaria Vaccine (1)

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

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

Stage of plasmodium

Antigens Salient features

Pre-erythrocytic Irradiated sporozoites , Circum Sporozoite Protein (CSP) or peptides, Liver stage Antigens -1 (LSA-1)

Stage/species specific; antibody blocks infection of liver; large immunising dose required; can abort an infection

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)

Specific for species and stage; Cannot abort an infection; Prevents invasion of erythrocytes, thus reducing severity of infection

Gametocytes & gametes

Pfs 25, 48/45k, Pfs 230 Prevents infection of mosquitoes; antibody to this antigen prevents either fertilization or maturation of gametocytes, zygotes or ookinetes; is of use in endemic areas but not suited for travelers; antibody blocks transmission cycle

Combined vaccine (cocktail)

SPf 66 (based on pre-erythrocytic and asexual blood stage proteins of Pf)

Based on incorporation of antigens from different stages into one vaccine to produce an immune response, blocking all stages of the parasite development

Source- WHO

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

Based on the circumsporoziote protein, but additionally has the recombinant protein covalently bound to a purified Pseudomonas aeruginosa toxin (A9).

A complete lack of protective immunity was demonstrated in those inoculated at early stage.

The study group used in Kenya had an 82% incidence of parasitaemia whilst the control group only had an 89% incidence.

Elicits a cellular response enabling the destruction of infected hepatocytes

Blocks transmission of the parasite from vertebrate host to mosquitoes. The highly attenuated NYVAC vaccinia virus strain has been utilized to

develop a multiantigen , multistage vaccine candidate for malaria. 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 of the P. falciparum antigens were

characterized during 1a clinical trial.

Most recently developed recombinant 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

Recent RTS,S Phase 2 trials on Children ages 1-4 in Mozambique

reduced clinical malaria episodes by 35% Reduced severe malaria episodes by 49%

Additional Phase 2 trials in infants and young children in several African countries

Phase 3 clinical trials in at least 6 African countries

2010 estimated submission for licensure If successful, vaccine licensure and use from

late 2011 (source:USAID,MVI)

Efficacy = 41% source- AMANET

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Days after vaccination

Efficacy data for RTS,S one two and three doses

controlRTS,S

Polymorphism and clonal variation in antigens of plasmodium

Parasite induced immuno-suppression Intracellular parasites Lack of MS proteins on infected RBCs.

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. MSA-I has 8

variants, MSA-2 has 10 and CSP has 6 variants

Multiple antigens, specific to species and stage

Determines the landscape features associated with the risk of vector-borne diseases.

Climatic factors associated with malaria risks.

Determines factors affecting vector abundance and mosquito breeding sites.