Data related to the CAVD 434/AUP 567 study manuscript are now available!

CAVD 434/AUP 567 study results were published in the May 2017 issue of the Journal of Virology.

Zurawski G, Shen X, Zurawski S, Tomaras GD, Montefiori DC, Roederer M, Ferrari G, Lacabaratz C, Klucar P, Wang Z, Foulds KE, Kao SF, Yu X, Sato A, Yates NL, LaBranche C, Stanfield-Oakley S, Kibler K, Jacobs B, Salazar A, Self S, Fulp W, Gottardo R, Galmin L, Weiss D, Cristillo A, Pantaleo G, Levy Y. Superiority in Rhesus Macaques of Targeting HIV-1 Env gp140 to CD40 versus LOX-1 in Combination with Replication-Competent NYVAC-KC for Induction of Env-Specific Antibody and T Cell Responses. J Virol. 2017 May 1;91(9):. PMID: 28202751.

See the abstract below or view publication

Analysis data for the neutralizing antibody, binding antibody (BAMA) and ICS assays are available in DataSpace for further exploration.

Abstract

We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P=0.01) than a group without poly ICLC. The responses were robust, cross-reactive, and contained antibodies specific to multiple epitopes within gp140 including the C1, C2, V1-3, C4, C5, and gp41 immuno-dominant regions. The DC-targeting vaccines also elicited modest serum Env-specific IgA responses. All groups gave serum neutralization activity limited to Tier 1 viruses and antibody dependent cytotoxicity responses (ADCC) after DC-targeting boosts. Furthermore, CD4⁺ and CD8⁺ T cell responses specific to multiple Env epitopes were strongly boosted by the DC-targeting vaccines + poly ICLC. Together, these results indicate that prime/boost immunization via NYVAC-KC and either αCD40.Env gp140/poly ICLC or αLOX-1.Env gp140/poly ICLC induced balanced antibody and T cell responses against HIV-1 Env. Co-administration of NYVAC-KC with the DC-targeting vaccines increased T cell responses, but had minimal effects on antibody responses except for suppressing serum IgA responses. Overall, compared to LOX-1, targeting Env to CD40 gave more robust T cell and serum antibody responses with broader epitope representation and greater durability.