VSSP modulate innate and adaptive immune response of HIV-1 infected patients: its correlation with clinical outcome.

FAINBOIM L; BILLORDO A; ARRUVITO L; GUTHMANN M; FINK V; KROLEWIECKI A; SARACCO M; GOMEZ E; GOLD S; CAHN P

Roma

Congreso; 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2011

# Background: We have demonstrated the adjuvant capacity of N-acetyl GM3 combined with Neisserial outer membrane to form very small proteoliposomes (VSSP). Now we performed a randomized, controlled phase II clinical trial, aimed to assess safety and capacity of NAcGM3/VSSP to improve innate and adaptive response of HIV-1 infected individuals, and its association with clinical outcome. HIV-1 infected patients with CD4 count >350 mm3, viral load between 3.000 and 60.000 copies/ml, and no indication for ART were included in Group A, (n=11), with no active treatment (control group) and Group B (n=11), receiving 11 I.M. injections of VSSP + Montanide.# Results: Immune monitoring performed at days 0, 56, 140 and 280. At day 280, the absolute number of NK cells expressing CD107a was 699±203 vs. 2293±368 (p=0001, and 119±47 vs. 737±165 (p=0.001) expressing IFN-γ when we compared group A with group B. Similarly, Group B (vaccine group) showed an increase of memory CD8+cells (62±3 vs. 47±2).At an 883 day follow up, 6 patients in Group A and only 2 patients of Group B have to initiate ART due to progression of the disease. Adverse events included mild local reactions at the injection site and mild to moderate shivers, fever and nausea. Treg frequency in Group B remains stable along treatment (5.7% day 0 and 6.1% (day 280). In contrast, Treg frequency in Group A increased significantly during follow up, most notably in patients who have to initiate ART due to progression of the disease (p=0.003).# Conclusion: NAcGM3/VSSP showed a relatively safe toxicity profile, without serious adverse events. An increase of Treg cells in the untreated group was associated with an earlier and greater number of patients requiring ART. NAcGM3/VSSP enhances both the NK function and the development of memory CD8+cells.