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

CD4 T Cells

All Aquiver

and

Poised for Action

One Year After the

STEP Vaccine



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



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 action) when Presented with their EpitopeImmune 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 action) when Presented with their EpitopeImmune Orchestra

CD4

CD4

IL2 cytokine

IFNg cytokine

TNFa cytokine

IL4 cytokine

IL10 cytokine

CD8

Killer CD8

T Cell

Killer Antibodies


Rationale
Rationale action) when Presented with their Epitope

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



Identifying cd4 epitopes using gag peptide pools
Identifying CD4 Epitopes Using Gag Peptide Pools Cells

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

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


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


Gag specific cd4 epitope mapping

IFN- Cellsg

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


To Investigate Gag Maxipool 21 & 22 Cells

We need to test the participant’s CD4 cells with the 10, single 15mer peptides that make up this Maxipool


DMSO Cells

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.


DMSO Cells

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.


DMSO Cells

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.


DMSO Cells

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.



Ptid 13837 s cd4 t cell gag epitope
PTID 13837’s CD4 T Cell Gag Epitope Cells

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 Cells

(481)

(477)

(293)

(477)

(41)

(297)

(465)

(385)

(73)

(261)

(297)

(429)

(465)

(373)

(37)

Gag gene



Vaccinated ptid 9952
Vaccinated PTID 9952 Post Vaccination

  • 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 Post Vaccinationone year post vaccination


Infected vaccinated ptid 9952 one year post vaccination1
Infected, vaccinated PTID 9952 Post Vaccinationone year post vaccination


Conclusion
Conclusion Post Vaccination

  • 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 Post Vaccination

  • 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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