Malaria vaccines

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Malaria vaccines
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Malaria the problem

• 2,200 million people exposed annually (1/4 of the
  worlds population)
• 300 million cases each year
• 9 out of 10 infections occur in Africa
• 2 3 million people die each year most of them
  are under 12 years old

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Malaria - current strategiesdrugs

• Drugs multidrug resistance spreading
• Combination therapy is necessary and expensive
• Few new antimalarial drugs in development
• No new antimalarial drugs on the market since
  70s (Artemensinin has been around for 2000 years)

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Malaria - current strategiesmosquitoes

• Insecticide impregnated bed nets
• SA/Mozambique collaboration is very promising
• Mosquito Genome - Genetically modified mosquitoes
  (long term application)
• Widespread and increasing insecticide resistance

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Malaria current strategy vaccine

• There is NO malaria vaccine
• Several malaria molecules are potential targets
  for inclusion in a vaccine

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Malaria vaccines candidate molecules

• Sporozoite stage
• Vaccine target - to induce immunity (antibodies)
  to block entrance into
• liver cells
• CSP-1, SSP-2, TRAP

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Malaria vaccine candidate molecules

• Liver stage
• Vaccine target - Th1CD4 - INF gamma, CD8 CTL
  and /- NK cell responses to destroy infected
  liver cells
• LSA-1, LSA-3, EXP-1

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Malaria vaccine candidate molecules

• Erythrocytic stage
• Vaccine target Stop RBC invasion, surface
  antigens for antibody dependent cellular
  cytotoxicity (ADCC) /- complement lysis, prevent
  cytoadherence
• MSP-1,2,3,4 AMA-1 RAP-1,2 EPB, EPA 175 RESA
  SERA-1 GLURP Pf 355 and PfEMP-1

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Cytoadherence Red blood cells infected with
malaria parasites stick to blood vessels in the
brain Lung, heart, liver, spleen and bone marrow.
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Malaria vaccine candidate molecules

• Sexual stage
• Vaccine target to prevent the development of
  the parasite in the mosquito. Antibodies /-
  complement
• Pfg 27 Pfs 25 Pfs 230 Pfs 28 Pfs 45/48

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Malaria vaccines on trial

• Irradiated sporozoites worked well in mice
• AND humans BUT
• Manuel Pattaroyo SPF 66 .
• RTSS sporozoite vaccine
• NyVacPf7 contains 7 malaria antigens
• in a vaccinia carrier
• DNA vaccines
• CDCNII MAL VAC-1 21 epitopes
• containing 11 B-cell, 3 CTL, 7 T-cell

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Malaria ideal vaccine ?

• Generates multiple antibody responses against
  multiple proteins at all stages of parasite
  life-cycle
• Protects people from disease and reduces parasite
  viability

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• We have identified the mouse malaria protein (and
  the falciparum protein) that triggered the T-cell
  clone
• Pf 386 ..

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Pf 386

• AT-cell clone grown from mice that had malaria
  protected T-cell deficient mice against malaria
• The mice made multiple antibody
• responses against different malaria
• antigens

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• T cell immunity in malaria infections
• Adoptive transfer of Antibodies
• Removal of B-cells
• Adoptive transfer of T-cells
• Adoptive transfer of Cloned T-cell
• T-cell clone protection and multiple antibody
  responses
• Proliferation of Cloned T-cell to malarial
  antigens
• Sequence of Pca. 96.
• Pca 96 falciparum homologue
• T-cell epitopes in Pca 96/Py and Pf 386.