1. A method of inducing an immune response against malaria in a mammal, which method comprises intramuscularly administering to a mammal a composition comprising a pharmaceutically acceptable carrier and either or both of:
(a) about 1\xd7106 particle units (pu) to about 1\xd71012 pu of a first adenoviral vector comprising an adenoviral genome comprising a left inverted terminal repeat (ITR), the E2A region, the E2B region, late regions L1-LS, and a right ITR, and a nucleic acid sequence encoding a P. falciparum circumsporozoite protein (CSP) operably linked to a human CMV promoter, and
(b) about 1\xd7106 particle units pu to about 1\xd71012 pu of a second adenoviral vector comprising an adenoviral genome comprising a left inverted terminal repeat (ITR), the E2A region, the E2B region, late regions L1-LS, and a right ITR, and a nucleic acid sequence encoding a P. falciparum apical membrane antigen 1 (AMA-1) antigen operably linked to a human CMV promoter,
wherein the composition is administered to the mammal one or more times, and wherein the nucleic acid sequence encoding a P. falciparum CSP andor the nucleic acid sequence encoding a P. falciparum AMA-1 are expressed to produce the CSP andor the AMA-1 in the mammal to induce an immune response against malaria.
2. The method of claim 1, wherein the composition comprises the first adenoviral vector and the second adenoviral vector.
3. The method of claim 2, wherein the composition comprises about 5\xd7109 pu to about 5\xd71010 pu of the first adenoviral vector and about 5\xd7109 pu to about 5\xd71010 pu of the second adenoviral vector.
4. The method of claim 3, wherein the composition comprises about 1\xd71010 pu of the first adenoviral vector and about 1\xd71010 pu of the second adenoviral vector.
5. The method of claim 2, wherein the composition comprises about 1\xd71010 pu to about 1\xd71011 pu of the first adenoviral vector and about 1\xd71010 pu to about 1\xd71011 pu of the second adenoviral vector.
6. The method of claim 5, wherein the composition comprises about 5\xd71010 pu of the first adenoviral and about 5\xd71010 pu of the second adenoviral vector.
7. The method of claim 1, wherein the composition comprises the first adenoviral vector and does not comprise the second adenoviral vector.
8. The method of claim 7, wherein the composition comprises about 1\xd71010 pu to about 1\xd71011 pu of the first adenoviral vector.
9. The method of claim 8, wherein the composition comprises about 5\xd71010 pu of the first adenoviral vector.
10. The method of claim 1, wherein the composition comprises the second adenoviral vector and does not comprise the first adenoviral vector.
11. The method of claim 10, wherein the composition comprises about 1\xd71010 pu to about 1\xd71011 pu of the second adenoviral vector.
12. The method of claim 11, wherein the composition comprises about 5\xd71010 pu of the second adenoviral vector.
13. The method of claim 1, wherein each of the first and second adenoviral vectors is replication-deficient and requires complementation of both the E1 region and the E4 region of the adenoviral genome for propagation.
14. The method of claim 13, wherein the adenoviral genome of each of the first and second adenoviral vectors lacks the entire E1 region and at least a portion of the E4 region of the adenoviral genome.
15. The method of claim 14, wherein the nucleic acid sequence encoding P. falciparum CSP is inserted into the deleted E1 region of the adenoviral genome of the first adenoviral vector.
16. The method of claim 15, wherein the nucleic acid sequence encoding the P. falciparum AMA-1 antigen is inserted into the deleted E1 region of the adenoviral genome of the second adenoviral vector.
17. The method of claim 1, wherein P. falciparum CSP comprises codons expressed more frequently in mammals than in Plasmodium.
18. The method of claim 17, wherein the nucleic acid sequence encoding P. falciparum CSP comprises SEQ ID NO: I0.
19. The method of claim 1, wherein the P. falciparum AMA-1 antigen comprises codons expressed more frequently in mammals than in Plasmodium.
20. The method of claim 19, wherein the nucleic acid sequence encoding P. falciparum AMA-1 antigen comprises SEQ ID NO: 16.
21. The method of claim 1, wherein the first adenoviral vector and the second adenoviral vector are the same.
22. The method of claim 1, wherein the mammal is a human.
23. The method of claim 1, wherein the composition is administered to the mammal once.
24. The method of claim 1, any of claims 1-23, wherein the composition is administered to the mammal twice.
25. The method of claim 1, wherein the method further comprises administering a boosting composition to the mammal, wherein the boosting composition comprises a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, andor a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof.
26. The method of claim 25, wherein the boosting composition is administered to the mammal at least 10 days after administration of the composition comprising the first andor second adenoviral vectors.
27. The method of claim 25, wherein the boosting composition is administered to the mammal four months after administration of the composition comprising the first andor second adenoviral vectors.
28. The method of claim 1, wherein the method further comprises administering a priming composition to the mammal, wherein the priming composition comprises a plasmid encoding a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, andor a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof.
29. The method of claim 1, wherein the method further comprises administering a priming composition to the mammal, wherein the priming composition comprises a viral vector encoding a P. falciparum circumsporozoite protein (CSP), or an immunogenic portion thereof, andor a P. falciparum apical membrane antigen 1 (AMA-1) antigen, or an immunogenic portion thereof.
30. The method of claim 28, wherein the priming composition is administered to the mammal at least 10 days before administration of the composition comprising the first andor second adenoviral vectors.
31. The method of claim 29, wherein the priming composition is administered to the mammal four months before administration of the composition comprising the first andor second adenoviral vectors.
32. The method of claim 29, wherein the priming composition is administered to the mammal at least 10 days before administration of the composition comprising the first andor second adenoviral vectors.
33. The method of claim 29, wherein the priming composition is administered to the mammal four months before administration of the composition comprising the first andor second adenoviral vectors.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. An apparatus for adjusting the speed of an engine, said apparatus comprising:
an actuator operably connected to a shaft having an axis and a distal end, said actuator being adapted to displace said shaft along said axis;
a bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said actuator such that said shaft extends generally toward said first bracket end;
said shaft further comprising a coupling operably connected to said shaft and adapted to connect to a throttle plate such that said displacement of said shaft moves said coupling, thereby moving said throttle plate without substantially moving said bracket; whereby
adjustment of said throttle cable moves said bracket, thereby causing said coupling to move said throttle plate, and actuation of said actuator causes said shaft to move said coupling thereby moving said throttle plate without substantially moving said bracket.
2. The apparatus according to claim 1, further comprising
a controller adapted to receive a signal corresponding to the operating speed of said engine and to control the actuation of said actuator whereby said controller causes said actuator to move said throttle plate automatically in response to said signal.
3. The apparatus according to claim 2, further comprising
a controller interface comprising a power switch and a display;
said power switch being adapted to activate and deactivate said controller and said display;
said display being electrically connected to said controller.
4. The apparatus of claim 1 wherein said actuator is a piezoelectric actuator.
5. The apparatus of claim 1 wherein said actuator comprises an electric motor.
6. The apparatus of claim 5 wherein said electric motor is a rotary stepper motor.
7. The apparatus of claim 5 wherein said electric motor comprises a diaphragm motor.
8. The apparatus of claim 1 wherein said actuator comprises a voice coil.
9. The apparatus of claim 1 wherein said actuator comprises a hydraulic cylinder.
10. The apparatus of claim 1 wherein said actuator comprises a pneumatic cylinder.
11. The apparatus of claim 1 wherein said bracket further comprises an aperture and at least a portion of said coupling extends through said aperture.
12. A system for synchronizing the rotational speeds of a plurality of engines of a vehicle, the system comprising:
a master engine and at least one slave engine;
an actuator assembly connected to said at least one slave engine, said actuator assembly comprising an actuator operably connected to a shaft having an axis and a distal end, said actuator being adapted to displace said shaft along said axis;
a bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said actuator such that said shaft extends generally toward said first bracket end;
said shaft further comprising a coupling operably connected to said shaft and adapted to connect to throttle plate operably connected to said slave engine such that said displacement of said shaft moves said coupling, thereby moving said throttle plate without substantially moving said bracket;
a master engine sensor capable of generating a signal corresponding to the rotational speed of said master engine;
a slave engine sensor capable of generating a signal corresponding to the rotational speed of said at least one slave engine;
a controller adapted to compare said signal corresponding to the rotational speed of said master engine and said signal corresponding to the rotational speed of said slave engine, and to cause said actuator to adjust said throttle plate of said slave engine to reduce said difference
whereby the rotational speed of said slave engine is synchronized to the rotational speed of said master engine.
13. The system of claim 12 wherein said controller is adapted to cause said actuator to adjust said throttle plate of said slave engine when said rotational speed of said master engine is within a predetermined range and said difference is less than a predetermined upper limit.
14. The system of claim 12 wherein further comprising
a plurality of slave engines, each said slave engine having a sensor capable of generating a signal corresponding to the rotational speed of said slave engine;
each said slave engine having an actuator assembly attached to said slave engine, said actuator assembly comprising an actuator operably connected to a shaft having an axis and a distal end, said actuator being adapted to displace said shaft along said axis;
a bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said actuator such that said shaft extends generally toward said first bracket end;
said shaft further comprising a coupling operably connected to said shaft and adapted to connect to the throttle plate of said slave engine such that said displacement of said shaft moves said coupling, thereby moving said throttle plate without substantially moving said bracket;
and wherein said controller is adapted to compare said signal corresponding to the rotational speed of said master engine and each said signal corresponding to the rotational speed of each of said slave engines, and to cause said actuator assembly attached to each said slave engine to adjust said throttle plate of said slave engine to reduce said difference
whereby the rotational speed of each said slave engine is synchronized to the rotational speed of said master engine.
15. The system of claim 12, further comprising
a controller interface comprising a power switch and a display;
said power switch being adapted to activate and deactivate said controller and said display;
said display being electrically connected to said controller.
16. The system of claim 12 wherein said actuator is a piezoelectric actuator.
17. The system of claim 12 wherein said actuator comprises an electric motor.
18. The system of claim 12 wherein said actuator comprises a hydraulic cylinder.
19. The system of claim 12 wherein said actuator comprises a pneumatic cylinder.
20. The system of claim 12 wherein said bracket further comprises an aperture and at least a portion of said coupling extends through said aperture.
21. An apparatus for adjusting the speed of an engine, said apparatus comprising:
an actuator operably connected to a shaft, said actuator being adapted to displace said shaft;
a first bracket comprising a first bracket end adapted to operably connect to a throttle cable and an opposing second bracket end attached to said shaft;
a second bracket assembly connected to said actuator and comprising a coupling adapted to connect to a throttle plate such that displacement of said shaft causes said actuator to move, thereby moving said second bracket assembly and said throttle plate without substantially moving said first bracket; whereby
adjustment of said throttle cable moves said first bracket, said shaft and said actuator, thereby causing said coupling to move said throttle plate, and actuation of said actuator causes said actuator to move said coupling.