Scientists from The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology (LJI) may have found the best delivery mode for a vaccine against HIV. The results of their new study show that “optimizing the mode and timing of vaccine delivery is crucial to inducing a protective immune response in a practical model,” according to a press release on the study
For their study
, published in the journal, Immunity
, the scientists found that, “administering the vaccine candidate subcutaneously and increasing the time intervals between immunizations improved the efficacy of the experimental vaccine and reliably induced neutralizing antibodies.” These antibodies are key in promoting an effective immune response as they inactivate an invading virus before it is able to set up shop in the body. According to the press release, these neutralizing antibodies, “have been notoriously difficult to generate for HIV.”
The scientists utilized outbred Indian Rhesus Macaques (Macaca mulatta
) for the study subjects. The macaques were, “immunized at 3 time points: week 0, week 8, and week 24. All immunizations were administered as split doses. Unless otherwise stated, each immunization consisted of two sc injections of 50 μg of Env trimer protein + 37.5 units (U) of ISCOMATRIX adjuvant (CSL), composed of cholesterol, phospholipid, and saponin, in sterile phosphate-buffered saline (PBS) diluent for a total of 100 μg of Env trimer protein + 75 U of ISCOMATRIX per immunization per animal,” according to the study methods. To produce a reliable neutralizing antibody response, multiple variations of the trimers and immunization protocols were used to discover the best strategy.
Because the scientists had observed in previous studies that, “follicular helper T cells help direct the maturation steps of antibody-producing B cells,” they administered “the vaccine subcutaneously versus the more conventional intramuscular route, and spac[ed] the injection at 8 weeks instead of the more common 4-6 weeks, [thus] reliably induc[ing] a strong functional immune response in all animals.”
Furthermore, the scientists found that, “using an osmotic pump to slowly release the vaccine over a period of 2 weeks resulted in the highest neutralizing antibody titers ever measured following SOSIP immunizations in non-human primates,” according to the press release. Admittedly not the most practical way to deliver a vaccine, the use of the osmotic pumps illustrated to the scientists that, “Depending on how we gave the vaccine, there was a bigger difference due to immunization route than we would have predicted,” according to quote in the press release from Matthias Pauthner, a graduate student and the study's co-lead author.
When speaking about the findings of this research, Professor Dennis R. Burton, PhD, who is also scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health's Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI stated in the press release, “This study is an important staging point on the long journey toward an HIV vaccine. The vaccine candidates we worked with here are probably the most promising prototypes out there, and one will go into people in 2018.”
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