1. A conjugate comprising:
i) epitope peptides of two neutralizing antibodies that bind to the membrane external proximal region (MPER) of HIV-1 gp41 and the V3 region of HIV 120, or
ii) carbohydrate antigens of gp120 conjugated to biotin.
2. The conjugate according to claim 1 wherein said conjugate comprises said epitope peptides and wherein said neutralizing antibodies are 2F5 and 4E10.
3. The conjugate according to claim 1 wherein said epitopes are linked to a spacer molecule.
4. The conjugate according to claim 3 wherein said spacer molecule comprises 3-5 G’s or \u2014(CH2)5\u2014.
5. The conjugate according to claim 1 wherein biotin is linked to the N terminal ends of said peptides.
6. The conjugate according to claim 1 wherein biotin is linked to the C terminal ends of said peptides.
7. The conjugate according to claim 1 wherein said conjugate comprises said epitope peptides and wherein said epitope peptides are selected from the group consisting of the epitope peptides set forth in FIG. 2.
8. The conjugate according to claim 1 wherein said conjugate is a B cell tetramer comprising peptides selected from the group consisting of the peptides set forth in FIG. 2.
9. The conjugate according to claim 1 wherein said conjugate is conjugated with phycoerythrin, keyhole limpet hemocyanin or ovalbumin.
10. A method of inducing broadly neutralizing antibodies against HIV in a patient in need thereof comprising administering to said patient an amount of the conjugate according to claim 1 sufficient to effect said induction.
11. The method according to claim 10 wherein said patient is a human.
12. The method according to claim 10 further comprising administering to said patient an adjuvant.
13. The method according to claim 12 wherein said adjuvant comprises Emulsign, oCpGs, a TLR4 against, a TLR7 agonist, or iRNAs that inhibit the tristetrapraline gene.
14. The method according to claim 10 wherein said method further comprises administering to said patient an agent that depletes T regulatory cells.
15. The method according to claim 14 wherein said agent comprises anti-CD25 antibodies, a GITR ligand or a CD40 ligand.
16. A composition comprising tetramers comprising nominal epitopes of the MPER region, the V3 region and carbohydrate oligomannoses that bind to 2G12.
17. A method of inducing neutralizing antibodies against HIV in a patient in need thereof comprising administering to said patient an amount of the composition according to claim 16 sufficient to effect said induction.
18. A composition comprising a biotinylated aptamer for an HIV epitope tetramerized with streptavadin.
19. A method of inducing an immune response in a patient in need thereof comprising administering to said patient an amount of the composition according to claim 18 sufficient to effect said induction.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1-25. (canceled)
26: An acceleration sensor, comprising:
a base having an XY-substrate surface substantially parallel to an XY flat surface and including an X-axis, a Y-axis, and a Z-axis, all of which being perpendicular to one another;
a beam portion having a frame shape arranged in a floating state above the XY-substrate surface of the base;
a beam supporting fixed portion arranged to support the beam portion on the base via supporting portions having an elongated shape disposed on both sides of the beam portion, each facing outwards along the X-axis direction;
a connecting portion having an elongated shape facing outwards along the Y-axis direction from each of two sides of the Y-axis direction of the beam portion in a state of floating above the XY-substrate surface of the base; and
a weight portion connected to a tip portion of each connection portion; wherein
the weight portion is arranged to be displaced in each of the X-axis direction, the Y-axis direction, and the Z-axis direction by bending deformation of the frame-shaped beam portion; and
the beam portion comprises an X-axis direction acceleration detecting portion arranged to detect acceleration in the X-axis direction based on the bending deformation of the beam portion originating in the X-axis direction displacement of the weight portion, a Y-axis direction acceleration detecting portion arranged to detect acceleration in the Y-axis direction based on the bending deformation of the beam portion originating in the Y-axis direction displacement of the weight portion, and a Z-axis direction acceleration detecting portion arranged to detect acceleration in the Z-axis direction based on the bending deformation of the beam portion originating in the Z-axis direction displacement of the weight portion.
27: The acceleration sensor according to claim 26, wherein
the center axis of each of the supporting portions is arranged substantially linearly on a common straight line, and the center axis of each of the connecting portions is arranged linearly on the common straight line; and
the beam portion is arranged symmetrically to an X-direction center line passing through the central axis of the supporting portion and symmetrically to a Y-direction center line which passes through the central axis of the connecting portion.
28: The acceleration sensor according to claim 26, wherein each of the Z-axis direction acceleration detecting portion, the Y-axis direction acceleration detecting portion, and the X-axis direction acceleration detecting portion are defined by a piezoresistant portion in which electrical resistance varies by changes in stress caused by changes in a shape of the beam portion.
29: The acceleration sensor according to claim 27, wherein each of the Z-axis direction acceleration detecting portion, the Y-axis direction acceleration detecting portion, and the X-axis direction acceleration detecting portion are defined by a piezoresistant portion in which electrical resistance varies by changes in stress caused by changes in a shape of the beam portion.
30: The acceleration sensor according to claim 28, wherein the X-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion and arranged on both sides of the connecting portions in a width direction thereof, the piezoresistant portions of the X-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the X-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the X-axis direction based on voltage differences output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the X-axis direction;
the Y-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion arranged on both sides of the supporting portions in a width direction thereof, the piezoresistant portions of the Y-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the Y-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Y-axis direction based on a voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Y-axis direction; and
the Z-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion, two of the piezoresistant portions of the Z-axis direction acceleration detecting portion are disposed on portions of the beam portion in which stress does not change when acceleration occurs, and the other two piezoresistant portions of the Z-axis direction acceleration detecting portion are arranged on one side of the beam portion on the supporting portion side, such that two voltage detectors are defined by electrically connecting piezoresistant portions which are arranged in close proximity to each other, and the four piezoresistant portions of the Z-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Z-axis direction based on a voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Z-axis direction.
31: The acceleration sensor according to claim 29, wherein the X-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion and arranged on both sides of the connecting portions in a width direction thereof, the piezoresistant portions of the X-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the X-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the X-axis direction based on voltage differences output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the X-axis direction;
the Y-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion arranged on both sides of the supporting portions in a width direction thereof, the piezoresistant portions of the Y-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the Y-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Y-axis direction based on a voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Y-axis direction; and
the Z-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion, two of the piezoresistant portions of the Z-axis direction acceleration detecting portion are disposed on portions of the beam portion in which stress does not change when acceleration occurs, and the other two piezoresistant portions of the Z-axis direction acceleration detecting portion are arranged on one side of the beam portion on the supporting portion side, such that two voltage detectors are defined by electrically connecting piezoresistant portions which are arranged in close proximity to each other, and the four piezoresistant portions of the Z-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Z-axis direction based on a voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Z-axis direction.
32: The acceleration sensor according to claim 26, wherein the frame-shaped beam portion has a substantially consistent thickness throughout the entire frame in the Z-axis direction.
33: The acceleration sensor according to claim 27, wherein the frame-shaped beam portion has a substantially consistent thickness throughout the entire frame in the Z-axis direction.
34: The acceleration sensor according to claim 28, wherein the frame-shaped beam portion has a substantially consistent thickness throughout the entire frame in the Z-axis direction.
35: The acceleration sensor according to claim 29, wherein the frame-shaped beam portion has a substantially consistent thickness throughout the entire frame in the Z-axis direction.
36: The acceleration sensor according to claim 30, wherein the frame-shaped beam portion has a substantially consistent thickness throughout the entire frame in the Z-axis direction.
37: The acceleration sensor according to claim 31, wherein the frame-shaped beam portion has a substantially consistent thickness throughout the entire frame in the Z-axis direction.
38: The acceleration sensor according to claim 26, wherein a thickness in the Z-axis direction of the beam portion in the vicinity of the supporting portion and in the vicinity of the connecting portion is greater than a thickness of other portions of the beam portion.
39: The acceleration sensor according to claim 27, wherein a thickness in the Z-axis direction of the beam portion in the vicinity of the supporting portion and in the vicinity of the connecting portion is greater than a thickness of other portions of the beam portion.
40: The acceleration sensor according to claim 28, wherein a thickness in the Z-axis direction of the beam portion in the vicinity of the supporting portion and in the vicinity of the connecting portion is greater than a thickness of other portions of the beam portion.
41: The acceleration sensor according to claim 29, wherein a thickness in the Z-axis direction of the beam portion in the vicinity of the supporting portion and in the vicinity of the connecting portion is greater than a thickness of other portions of the beam portion.
42: The acceleration sensor according to claim 30, wherein a thickness in the Z-axis direction of the beam portion in the vicinity of the supporting portion and in the vicinity of the connecting portion is greater than a thickness of other portions of the beam portion.
43: The acceleration sensor according to claim 31, wherein a thickness in the Z-axis direction of the beam portion in the vicinity of the supporting portion and in the vicinity of the connecting portion is greater than a thickness of other portions of the beam portion.
44: The acceleration sensor according to claim 26, wherein a reinforcing portion is arranged in a space inside the frame of the frame-shaped beam portion, which links the supporting portions on both sides of the beam portion, and both ends of the reinforcing portion are each connected to the frame-shaped beam portion.
45: The acceleration sensor according to claim 26, wherein the supporting portion is connected to a beam-supporting fixed portion via an elastic portion, the elastic portion elastically changing shape corresponding to distortions of the beam-supporting fixed portion and decreasing stresses which originate from the distortion of the beam-supporting fixed portion and which are applied to the supporting portion from the beam-supporting fixed portion.
46: The acceleration sensor according to claim 44, wherein the supporting portion is connected to a beam-supporting fixed portion via an elastic portion, the elastic portion elastically changing shape corresponding to distortions of the beam-supporting fixed portion and decreasing stresses which originate from the distortion of the beam-supporting fixed portion and which are applied to the supporting portion from the beam-supporting fixed portion.
47: The acceleration sensor according to claim 45, wherein the elastic portion includes a beam which is elongated so as to intersect with a supporting portion elongation direction, both ends of the beam of the elastic portion being fixed to the beam-supporting fixed portion, and the supporting portion being connected to the beam of the elastic portion and supported by the beam-supporting fixed portion.
48: The acceleration sensor according to claim 46, wherein the elastic portion includes a beam which is elongated so as to intersect with a supporting portion elongation direction, both ends of the beam of the elastic portion being fixed to the beam-supporting fixed portion, and the supporting portion being connected to the beam of the elastic portion and supported by the beam-supporting fixed portion.
49: The acceleration sensor according to claim 28, wherein
the X-axis direction acceleration detecting portion includes a total of four piezoresistant portions disposed on the beam portion and arranged on both sides of the connecting portion side, the piezoresistant portions of the X-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the X-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the X-axis direction based on the voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the X-axis direction;
the Y-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion and arranged on both sides of the supporting portion, and the piezoresistant portions of the Y-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the Y-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Y-axis direction based on the voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Y-axis direction; and
the Z-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion and arranged each on both sides of the supporting portion, and two voltage detectors are defined by electrically connecting the piezoresistant portions of the Z-axis direction acceleration detecting portion which are arranged on both sides of the supporting portion, and the four piezoresistant portions of the Z-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Z-axis direction based on the voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Z-axis direction.
50: The acceleration sensor according to claim 29, wherein
the X-axis direction acceleration detecting portion includes a total of four piezoresistant portions disposed on the beam portion and arranged on both sides of the connecting portion side, the piezoresistant portions of the X-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the X-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the X-axis direction based on the voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the X-axis direction;
the Y-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion and arranged on both sides of the supporting portion, and the piezoresistant portions of the Y-axis direction acceleration detecting portion are electrically connected with each other to define two voltage detectors, and the four piezoresistant portions of the Y-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Y-axis direction based on the voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Y-axis direction; and
the Z-axis direction acceleration detecting portion includes four piezoresistant portions disposed on the beam portion and arranged each on both sides of the supporting portion, and two voltage detectors are defined by electrically connecting the piezoresistant portions of the Z-axis direction acceleration detecting portion which are arranged on both sides of the supporting portion, and the four piezoresistant portions of the Z-axis direction acceleration detecting portion define a bridge circuit arranged to detect acceleration in the Z-axis direction based on the voltage difference output from each of the two voltage detectors when the beam portion changes shape due to acceleration in the Z-axis direction.