Co-administration of Rapamycin with a DNA/MVA SIV Vaccine Improves Memory CD8 T Cell Response

Shanmugalakshmi Sadagopal; Kasey Stokdyk; Suefen Kwa; Rahul Basu; Sailaja Gangadhara; Rafi Ahmed; Smita S. Iyer; Koichi Araki; Rama Rao Amara

doi:10.1172/jci.insight.193752

Co-administration of Rapamycin with a DNA/MVA SIV Vaccine Improves Memory CD8 T Cell Response

Shanmugalakshmi Sadagopal,¹ Kasey Stokdyk,² Suefen Kwa,² Rahul Basu,² Sailaja Gangadhara,¹ Rafi Ahmed,³ Smita S. Iyer,¹ Koichi Araki,³ and Rama Rao Amara¹

Published April 23, 2026 - More info

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Abstract

Inhibiting the mammalian target of rapamycin (mTOR) during acute viral infection generates highly functional memory CD8 T cells. We investigated the effects of inhibiting mTOR by using rapamycin during the effector and contraction phases of the immune response to a DNA prime and Modified Vaccinia Ankara (MVA) boost SIV vaccination in rhesus macaques. Rapamycin administered either during MVA boosts alone (DM_R) or during both primes and boosts (D_RM_R) reduced the contraction of effector CD8 T cells, resulting in higher frequencies of SIV-specific memory CD8 T cells with enhanced quality as indicated by expression of Bcl-2 and CD127. Additionally, rapamycin reduced the frequency of proliferating CCR5+ CD4 T cells in the blood following the MVA boost. Post SIV251 infection, rapamycin-treated macaques demonstrated marked expansion of SIV-specific CD8 T cells (reaching up to 50% in blood and 25% in gut). The heightened expansion of SIV-specific CD8 T cells in the DMR group was associated with markedly lower (2-logs compared to unvaccinated and 1-log compared to DM) peak viral load in the gut and set-point viremia, along with improved survival post infection. Thus, inhibiting the mTOR pathway during MVA boosts of a DNA/MVA vaccine enhances vaccine efficacy by improving memory CD4 and CD8 T cell function.

Co-administration of Rapamycin with a DNA/MVA SIV Vaccine Improves Memory CD8 T Cell Response

Shanmugalakshmi Sadagopal,¹ Kasey Stokdyk,² Suefen Kwa,² Rahul Basu,² Sailaja Gangadhara,¹ Rafi Ahmed,³ Smita S. Iyer,¹ Koichi Araki,³ and Rama Rao Amara¹

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Co-administration of Rapamycin with a DNA/MVA SIV Vaccine Improves Memory CD8 T Cell Response

Shanmugalakshmi Sadagopal,1 Kasey Stokdyk,2 Suefen Kwa,2 Rahul Basu,2 Sailaja Gangadhara,1 Rafi Ahmed,3 Smita S. Iyer,1 Koichi Araki,3 and Rama Rao Amara1

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Shanmugalakshmi Sadagopal,¹ Kasey Stokdyk,² Suefen Kwa,² Rahul Basu,² Sailaja Gangadhara,¹ Rafi Ahmed,³ Smita S. Iyer,¹ Koichi Araki,³ and Rama Rao Amara¹