TABLE 1.
Immunization groups and experimental designa
Treatment group | No. of animals | Vaccine | Subgroup | Animals | Prime particlesb | Boost particlesc | SIVmac251 challenge (AID50)d |
---|---|---|---|---|---|---|---|
Vaccines | 6 | TRIP-SIVmac239 GAG | Low dose | 20022, 20089 | 2.5 × 107 TU | 1.2 × 108 TU | 500 |
Medium dose | 20293, 20056 | 1 × 108 TU | 1.2 × 108 TU | 500 | |||
High dose | 20195, 20158 | 2.5 × 108 TU | 1.2 × 108 TU | 500 | |||
GFP control | 2 | TRIP-GFP | 21544, 20456 | 6,863 ng of p24 | 6,018 ng of p24 | 500 | |
Naive | 4 | None | 15661, 14184, 15885, 14468 | None | None | 500 |
Twelve outbred males and adult cynomolgus macaques (Macaca fascicularis) from the Indian Ocean Island of Mauritius were included in the preclinical trial. They were negative for SIV, herpesvirus B, filovirus, STLV-1, SRV-1, SRV-2, measles virus, hepatitis B-HbsAg, and hepatitis B-HBcAb before inclusion in the study. Immunizations, blood collections, and challenges were handled in accordance with EU guidelines for experiments using nonhuman primates (document 2001-486) and approved by the Institut Pasteur review board. Immunizations were done by subcutaneous injections on days 0 and 79 of lentiviral particles pseudotyped with two different envelopes: the glycoproteins G from two non-cross-reactive VSV serotypes: Indiana and New Jersey. The doses of lentiviral vector particles were expressed as TU/animal and as ng of p24/animal. Six animals were immunized with three doses (low, medium, and high) of lentiviral vectors encoding a nonsecreted form of SIVmac239 GAG (myristoylation deficient, Δmyr). Because of the absence of a dose response after the first injection, all six vaccinated animals received the same medium dose of vector for the second injection. Two control animals were immunized with lentiviral vector encoding an irrelevant antigen, GFP, at the same p24 dose as the high-dose relevant subgroup. Vaccinated, GFP control, and unvaccinated macaques were challenged intrarectally at 76 days postboost with a high dose of pathogenic SIVmac251 (500 AID50) compared to 20 to 50 AID50 usually used in studies of the protective efficacy of vaccines. The virus stock was from A.-M. Aubertin, Université Louis Pasteur, Strasbourg, France. The GAG from SIVmac251 used for the challenge closely matches the GAG from SIVmac239 encoded by the vaccine (homologous challenge).
Pseudotyped with VSV-G Indiana at day 0.
Pseudotyped with VSV-G New Jersey at day 79 postprime.
At day 76 postboost.