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Malaria vaccine
- 2. No commercially available malaria vaccine at the present time. RTS,S/AS01 is the most advanced vaccine candidate against 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
- 6. To Combat Malaria Multi-intervention approach may be the best
- 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
- 10. MalariaLifeCycle
- 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
- 14. Antigens Vaccine contain antigens They are the targets of the immune system Different antigenic targets are expressed at different stages of life
- 15. Immune Response Triggered by the parasite •Anti-parasitic immunity •Anti-toxic immunity
- 16. Immune Response Anti-parasitic immunity • Cell mediated immunity • Humoral immunity Anti-toxic immunity • Suppress the immune response • That induce symptoms • That reduce the effect of parasitic toxic products
- 17. Immune Response In liver stage Blood stage Sexual stage
- 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
- 22. NEW VACCINE DEVELOPMENTS Pre- erythrocyctic vaccine Blood stage vaccine Transmission blocking vaccine
- 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
- 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.
- 28. Thank You