Ruprecht: Con rming the Ef cacy of Virosomes Targeting gp41 in Indian Rhesus Macaques
The larger strategic goal of this grant is to develop a safe, effective vaccine against HIV/AIDS capable of
protecting a significant fraction of virus-exposed individuals from persistent, systemic infection. Vaccine
development will be done in collaboration with Mymetics Corporation that is developing vaccines based on
virosomes, a vaccine platform that has already been used in humans for over 10 years with an excellent
safety record. Virosomes have been engineered to display either P1, a peptide containing the membrane-
proximal external region (MPER) of gp41, the transmembrane protein of HIV, or rgp41, a truncated version of
gp41. The resulting virosomes are termed virosome-P1 or virosome-rgp41, respectively. When the combination of the two HIV gp41-based virosomes was tested in Chinese rhesus monkeys (RMs), all animals were
protected from persistent systemic infection after multiple challenges with a simian-human immunodeficiency
virus (SHIV) that carries the HIV envelope.
This program now seeks to confirm these results in Indian RMs that are commonly used in AIDS research
and better characterized genetically. In parallel, we will also assess how well one of the vaccine components, virosome-P1, can protect Indian RMs when used as single agent. Of note, virosome-P1 has already
undergone successful Phase I testing in healthy women.
Work towards achieving the larger strategic goal is envisioned in different phases. This 18-month award
provides detailed information for the first phase of evaluating the efficacy of the indicated virosomes, either
in combination or using virosome-P1 as a single agent, to protect Indian RMs against a mucosal challenge.
Ensuing phases would examine the Indian rhesus model for correlates of protection, longevity of protective
responses, and breadth of cross-clade protection – all relevant preclinical evaluations that could be performed
in parallel with early stages of clinical development.
This program is a collaboration led by Ruth Ruprecht, MD, PhD (Texas Biomedical Research Institute and
Southwest National Primate Research Center), with the participation of Mymetics Corp, under the direction
of Ronald Kempers. The grant was awarded in October, 2014, with an initial agreement length of 18 months.
1. Produce virosomes carrying either P1 or rgp41, in suitable containers/devices for injection and intranasal administration, and passing all QC parameters that have been previously shown to ensure immunogenicity of the products.
2. Perform immunogenicity and ef cacy studies in Indian-origin RMs using the same combination of virosome-P1 + virosome-rgp41 tested previ- ously. Vaccines will be administered intramuscularly and intranasally over a 6-month schedule; 5 weeks after the last immunization, the animals will undergo repeated low-dose intra-vaginal challenges with the same R5 tier 2 SHIV that had been used in the original study, SHIVSF162P3.
3. Evaluate the immunogenicity and ef cacy of virosome-P1 as a single agent to protect Indian RMs against repeated low-dose intravaginal SHIVSF162P3 challenges.