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All Aquiver and Poised for Action One Year After the STEP Vaccine

CD4 T Cells. All Aquiver and Poised for Action One Year After the STEP Vaccine. A quick immunology overview. HIV (or parts of HIV from a vaccine) are Engulfed by Surveillance Cells. HIV, or vaccine components. Surveillance Cell.

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All Aquiver and Poised for Action One Year After the STEP Vaccine

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  1. CD4 T Cells All Aquiver and Poised for Action One Year After the STEP Vaccine

  2. A quick immunology overview

  3. HIV (or parts of HIV from a vaccine) are Engulfed by Surveillance Cells HIV, or vaccine components Surveillance Cell

  4. HIV (or parts of HIV from a vaccine) are Engulfed by Surveillance Cells

  5. HIV (or parts of HIV from a vaccine) are Engulfed by Surveillance Cells

  6. Surveillance Cells Cut Up Virus/Vaccine Parts into Different Little Bits

  7. Little Bits of Virus (or Vaccine Parts) are Presented on the Surface of the Surveillance Cells EPITOPES (peptides- 15 amino acids long)

  8. CD4 T Cells become Excited (all aquiver and poised for action) when Presented with their Epitope CD4 CD4 EPITOPE (peptide) EPITOPE (peptide)

  9. CD4 T Cells are the Conductors of the Immune Orchestra CD4 CD4 IL2 cytokine IFNg cytokine TNFa cytokine (polyfunctional) IL4 cytokine IL10 cytokine

  10. CD4 T Cells are the Conductors of the Immune Orchestra CD4 CD4 IL2 cytokine IFNg cytokine TNFa cytokine IL4 cytokine IL10 cytokine CD8 Killer CD8 T Cell Killer Antibodies

  11. Rationale WHY CD4? • CD4 T cells help optimize the killing activity of CD8 T cells • CD4 T cells enhance antibody responses WHY STEP? • Important to work out what went right with this vaccine regime

  12. Need to Know Which Parts of the Vaccine Excited the CD4 T Cells

  13. Identifying CD4 Epitopes Using Gag Peptide Pools Gag Master pool Maxipools 1&2 23&24 .............. 24 23 Minipools 1 2 .............. 23.1, 23.2, 23.3, 23.4, 23.5 24.1, 24.2, 24.3, 24.4, 24.5, 24.6, 24.7 1.1, 1.2, 1.3, 1.4, 1.5 2.1, 2.2, 2.3, 2.4, 2.5 Single 15mers overlapping by 11aa1. MGARASVLSGGELDR (epitope peptide) 2. ASVLSGGELDRWEKI (epitope peptide) 1,2,3,4,5,6,7,8,9,10..............111,112,113,114,115,116,117,118,119,120,121,122 Gag gene MGARASVLSGGELDRWEKI LTSLRSLFGNDPSSQ ............................................................

  14. A representative example of identifying the epitope that elicited a Gag-specific CD4 T cell response one year post STEP vaccination(PTID 13837)

  15. IFN-g IL-2 DMSO Gag Master Pool Gag-specific CD4 epitope mapping Gag Maxipool 1&2 Gag Maxipool 9&10 Gag Maxipool 21&22 Gag Maxipool 23&24

  16. To Investigate Gag Maxipool 21 & 22 We need to test the participant’s CD4 cells with the 10, single 15mer peptides that make up this Maxipool

  17. DMSO IFN-g Gag single 15mer 22.2 IL-2 TNF-a To Investigate Gag Maxipool 21 & 22 Gag single 15mer peptide, 22.2, elicits no more CD4 response than the DMSO negative control, therefore is negative.

  18. DMSO IFN-g Gag single 15mer 22.3 TNF-a IL-2 To Investigate Gag Maxipool 21 & 22 Gag single 15mer peptide, 22.3, elicits a higher, CD4 response than the DMSO negative control, therefore is positive.

  19. DMSO IFN-g Gag single 15mer 22.4 TNF-a IL-2 To Investigate Gag Maxipool 21 & 22 Gag single 15mer peptide, 22.4, elicits a higher, CD4 response than the DMSO negative control, therefore is positive.

  20. DMSO IFN-g Gag single 15mer 22.5 TNF-a IL-2 To Investigate Gag Maxipool 21 & 22 Gag single 15mer peptide, 22.5, elicits no more CD4 response than the DMSO negative control, therefore is negative.

  21. To Investigate Gag Maxipool 21 & 22

  22. PTID 13837’s CD4 T Cell Gag Epitope Gag 15mer peptide 22.4 Gag 15mer peptide 22.3 R429QANFLGKIWPSHKGRPGN447 Gag gene

  23. Relative Positions of Gag CD4 Epitopes (481) (477) (293) (477) (41) (297) (465) (385) (73) (261) (297) (429) (465) (373) (37) Gag gene

  24. Cytokine Profile of Epitope-Specific CD4 T Cells One Year Post Vaccination

  25. Vaccinated PTID 9952 • This participant had a vaccine-induced CD4 T cell response to Gag epitope 24.5 and 24.6 (from maxipool 23 & 24). • This participant then became infected with HIV. • Will this vaccine-induced response still be dominant after infection?

  26. Infected, vaccinated PTID 9952 one year post vaccination

  27. Infected, vaccinated PTID 9952 one year post vaccination

  28. Conclusion • Low, vaccine-induced Gag-specific CD4 T cell responses were identified, at one year post vaccination, in uninfected participants in the STEP vaccine trial • Two responses in some participants • Epitopes located along entire length of Gag gene • Most common Gag-specific CD4 T cell response at one year post vaccination was the release of two cytokines, IL2 and TNFa – degree of polyfunctionality. • Some vaccine-induced CD4 responses dominate after infection • Overall, data suggests utility of these vaccine-induced, CD4 T cell responses.

  29. Acknowledgements • Trial participants and the CAB • Repository technicians • SAL • Endpoints • Evan Thomas and Janice Chen • Nicole Frahm • Steve de Rosa • Julie McElrath • National Health & Medical Research Council (NHMRC), Australia

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