PT  - JOURNAL ARTICLE
AU  - Giulia Calenda
AU  - Ines Frank
AU  - Géraldine Arrode-Brusés
AU  - Amarendra Pegu
AU  - Keyun Wang
AU  - James Arthos
AU  - Claudia Cicala
AU  - Brooke Grasperge
AU  - James L. Blanchard
AU  - Stephanie Maldonado
AU  - Kevin Roberts
AU  - Agegnehu Gettie
AU  - Anthony S. Fauci
AU  - John R. Mascola
AU  - Elena Martinelli
TI  - Protection against repeated vaginal SHIV challenges by a combination of VRC01 and an anti-α<sub>4</sub>β<sub>7</sub> antibody
AID  - 10.1101/365551
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 365551
4099  - http://biorxiv.org/content/early/2018/07/09/365551.short
4100  - http://biorxiv.org/content/early/2018/07/09/365551.full
AB  - Passive transfer of VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Protection against repeated rectal challenges decreases with decreased antibody levels weeks after infusion. Protection against repeated vaginal challenges has not been tested; however, it is expected to decrease similarly. Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and minimized the decline of CD4+ T cells. To investigate the impact of combining VRC01 and Rh-α4β7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-α4β7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000TCID50) of SHIVAD8-EO. The combination Rh-α4β7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-α4β7-treated macaques maintained higher CD4+ T cell counts compared to macaques in the other groups and exhibited lower rectal SIV-DNA loads compared to the controls. Interestingly, VRC01-Rh-α4β7-treated macaques had less IL-17 producing cells in blood and gut tissue during the acute phase and higher T cell responses to the V2-loop of the SHIVAD8-EO envelope compared to the other groups. The combination of suboptimal amounts of VRC01 and Rh-α4β7 delayed infection, altered anti-viral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4β7 on SIV/HIV infection and anti-viral immune responses is warranted and may lead to novel preventive and therapeutic strategies.