seder

Question 1

Immunization with infected bites

Answer 1

Sustained pre-erythrocyte malarial immunity can be achieved through administration of sporozooites through the bites of 1000 irradiated mosquitos. . . which sounds aweful.

Antibodies against PFCSP or PfSPZ have been detected

Question 2

Plasmodium falciparum

Answer 2

cause of malaria

Question 3

RTS,S/AS01

Answer 3

Subunit vaccine for malarial infection that prevents advanced malaria:
2 weeks after last dose 50% protection
5 months - 22% infection
in infants 6-12 weeks of age - 30% protection from clinical/severe malaria

Question 4

CHMI

Answer 4

Controlled human malarial infection. yikes

Question 5

Vaccination with Atenuated PfSPZ

Answer 5

Requires 1.35e5 to protect (1e3 or 1e4 did not protect)
Elicites more antibodies that give higher ISI in protected patients.
antibodies not detected against other malarial stages

Question 6

CSP

Answer 6

Circumsporozoite protein
Major surface protein on SPZ
Target for neutralizing antibodies (prevents invasion in hepatocytes)

Question 7

Mechansm of RTS,S/AS01 protection

Answer 7

Neutralizing antibodies against CSP - for irradiated mosquitos antibodies only mediate some protection

Question 8

ISI

Answer 8

Inhibition of Sporozoite invasion
Antibodies in PfSPZ
Neutralization determined by the serums ability to inhibit sporozoite invasion of a hepatocyte line.

Question 9

Cellular mediators of malarial immunity

Answer 9

CD8+ T cells and IFNg are critical

CD4, gammadelta and NK cells can also play a role.

Question 10

Cellular responses to PfSPZ

Answer 10

memory CD4 cells produce IFNg IL2 or TNF. memory CD8 cells produce IFNg and TNF
No correlation between CD4 IFNg and protection
More consistent and robust CD8 IFN g in the protected

Gamma deltas respond at a higher frequence in the patients who are protected, but the proportion of gamma producers remains the same.

Question 11

memory subsets

Answer 11

malaria-Specific cells detected in
CD4+ - Tcm and Tem

CD8 in Tem and Tte

malarial specific CD8 t cells expressed higher levels of Gamma when people were protected

Question 12

Overall summary

Answer 12

more PfSPZ-specific cells in CD8+ IFNg+ cells in protected people as well as gamma delta cells.
efficacy is considerably higher than in subunit vaccines
is it due to multiple low-level antigen specific responses or from robust responses to a few immunodominant but unidentified antigens
antibodies were made and increased in a dose-dependent manner. not clear whether they are contributing to protection or should just be used to predict vaccine take.