All aquiver and poised for action one year after the step vaccine
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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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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


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 parts of HIV from a vaccine) are Engulfed by Surveillance Cells

HIV, or vaccine components

Surveillance Cell


Hiv or parts of hiv from a vaccine are engulfed by surveillance cells1

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


Hiv or parts of hiv from a vaccine are engulfed by surveillance cells2

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


Surveillance cells cut up virus vaccine parts into different little bits

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


Little bits of virus or vaccine parts are presented on the surface of the surveillance cells

Little Bits of Virus (or Vaccine Parts) are Presented on the Surface of the Surveillance Cells

EPITOPES

(peptides-

15 amino acids long)


Cd4 t cells become excited all aquiver and poised for action when presented with their epitope

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

CD4

CD4

EPITOPE

(peptide)

EPITOPE

(peptide)


Cd4 t cells are the conductors of the immune orchestra

CD4 T Cells are the Conductors of the Immune Orchestra

CD4

CD4

IL2 cytokine

IFNg cytokine

TNFa cytokine

(polyfunctional)

IL4 cytokine

IL10 cytokine


Cd4 t cells are the conductors of the immune orchestra1

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


Rationale

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


Need to know which parts of the vaccine excited the cd4 t cells

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


Identifying cd4 epitopes using gag peptide pools

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

............................................................


All aquiver and poised for action one year after the step vaccine

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


Gag specific cd4 epitope mapping

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


All aquiver and poised for action one year after the step vaccine

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


All aquiver and poised for action one year after the step vaccine

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.


All aquiver and poised for action one year after the step vaccine

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.


All aquiver and poised for action one year after the step vaccine

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.


All aquiver and poised for action one year after the step vaccine

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.


All aquiver and poised for action one year after the step vaccine

To Investigate Gag Maxipool 21 & 22


Ptid 13837 s cd4 t cell gag epitope

PTID 13837’s CD4 T Cell Gag Epitope

Gag 15mer peptide 22.4

Gag 15mer peptide 22.3

R429QANFLGKIWPSHKGRPGN447

Gag gene


Relative positions of gag cd4 epitopes

Relative Positions of Gag CD4 Epitopes

(481)

(477)

(293)

(477)

(41)

(297)

(465)

(385)

(73)

(261)

(297)

(429)

(465)

(373)

(37)

Gag gene


Cytokine profile of epitope specific cd4 t cells one year post vaccination

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


Vaccinated ptid 9952

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?


Infected vaccinated ptid 9952 one year post vaccination

Infected, vaccinated PTID 9952 one year post vaccination


Infected vaccinated ptid 9952 one year post vaccination1

Infected, vaccinated PTID 9952 one year post vaccination


Conclusion

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.


Acknowledgements

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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