PROJECT SUMMARY – OVERALL
This multi-PI application is a collaboration between Mymetics and the Texas Biomedical Research Institute
(TxBiomed), with Drs. Sylvain Fleury (Project 1 Lead; Mymetics) and Ruth Ruprecht (Project 2 Lead; TxBiomed)
serving as PIs. We seek to bring a promising HIV/AIDS vaccine approach to the clinic. The vaccine is based
upon influenza virosomes, enveloped virus-like particles that display on their surface elongated HIV gp41
peptides (virosome-P1) or recombinant truncated HIV gp41 (virosome-rgp41). Mymetics' Phase I clinical trial
with virosome-P1 in healthy women showed safety and immunogenicity. Two independent nonhuman primate
(NHP) studies demonstrated the safety and high efficacy of the combination of virosome-P1 + virosome rgp41
against repeated low-dose intravaginal challenges with a tier 2 R5 SHIV in Chinese and Indian-origin rhesus
macaques (RMs). In the latter, 78-87% efficacy was noted when the SHIV challenge dose was ~7x104 times the
median HIV inoculum in male-to-female HIV transmission. However, when this HIV inoculum was exceeded 105-
fold by an even higher SHIV inoculum, protection in Indian RMs was lost, implying a threshold effect whereby
vaccine-induced mucosal antibodies were unable to ward off the higher number of invading SHIV particles. The
soluble vaccine used in both NHP studies was unadjuvanted. To improve immunogenicity, Mymetics has
embedded the toll-like receptor (TLR)7/8 adjuvant 3M-052 into virosomal envelopes. Moreover, Mymetics has
developed a powdered form of virosomes that is no longer cold-chain dependent and can be administered as
intranasal (IN) spray, sublingual (SL) tablets, or packaged into oral capsules. We hypothesize that these novel
solid virosome formulations are significantly more immunogenic, particularly when administered via mucosal
routes, than the unadjuvanted liquid form used earlier in NHPs. The Specific Aims of this IPCAVD project are to:
1. Assess the immunogenicity of the new vaccine candidates, the newly 3M-052-adjuvanted HIV virosome-P1
and virosome-rgp41, under solid dosage forms delivered IN, SL, or orally to Indian RMs in order to select the
two most immunogenic formulations for subsequent mucosal prime/mucosal boost immunization.
2. Assess the efficacy of the cold-chain independent virosomal vaccine delivered by combined mucosal
immunization routes against repeated intrarectal challenges with the heterologous R5 clade B SHIVSF162P3.
Protected RMs will be rechallenged with an R5 tier 2 clade C SHIV.
3. Optimize the GMP manufacturing process for the selected virosomal formulations for mucosal delivery, and
4. Perform toxicology studies to show good safety profiles of the adjuvanted, solid-form vaccines given by
selected mucosal routes – and generate GMP vaccine for a Phase I trial to be conducted with the HVTN.
Our vaccine development plans represent major advances, as the novel needle-free, solid vaccine dosage forms
are cold-chain independent and will be mucosally delivered – unique aspects that make the novel virosomal
vaccines especially attractive for the developing world, where the AIDS epidemic remains a serious problem.