Protection against repeated vaginal SHIV challenges by a combination of VRC01 and an anti-α4β7 antibody

Calenda, G.; Frank, I.; Arrode-Bruses, G.; Pegu, A.; Wang, K.; Arthos, J.; Cicala, C.; Grasperge, B.; Blanchard, J. L.; Maldonado, S.; Roberts, K.; Gettie, A.; Fauci, A. S.; Mascola, J. R.; Martinelli, E.

doi:10.1101/365551

bioRxiv · 10.1101/365551

Protection against repeated vaginal SHIV challenges by a combination of VRC01 and an anti-α4β7 antibody

Calenda, G.·Frank, I.·Arrode-Bruses, G.·Pegu, A.·Wang, K.·Arthos, J.·Cicala, C.·Grasperge, B.·Blanchard, J. L.·Maldonado, S.·Roberts, K.·Gettie, A.·Fauci, A. S.·Mascola, J. R.·Martinelli, E.

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Abstract

VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-4{beta}7 mAb (Rh-4{beta}7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-4{beta}7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-4{beta}7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000TCID50) of SHIVAD8-EO. The combination Rh-4{beta}7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-4{beta}7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to the controls. Interestingly, VRC01-Rh-4{beta}7-treated macaques had less IL-17 producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8- EO envelope in the VRC01-Rh-4{beta}7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-4{beta}7 delayed infection, altered anti-viral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-4{beta}7 on SIV/HIV infection and anti-viral immune responses is warranted and may lead to novel preventive and therapeutic strategies.\n\nShort summaryA combination of VRC01 and Rh-4{beta}7 significantly delayed SHIV acquisition, protected CD4 counts, decreased gut viral load and modified the immune response to the virus.

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Calenda, G., Frank, I., Arrode-Bruses, G., Pegu, A., Wang, K., Arthos, J., Cicala, C., Grasperge, B., Blanchard, J. L., Maldonado, S., Roberts, K., Gettie, A., Fauci, A. S., Mascola, J. R., Martinelli, E.. 2018-07-09. Protection against repeated vaginal SHIV challenges by a combination of VRC01 and an anti-α4β7 antibody. https://doi.org/10.1101/365551

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