A quadrivalent mosaic HIV vaccine induced greater immune responses on a variety of assays and against several HIV clades than its trivalent equivalent, Daniel J. Stieh, Ph.D., of Janssen Vaccines & Prevention BV reported at the HIVR4P conference in Madrid, Spain. This quadrivalent version will be used in future vaccine studies, he added.
One of the ways a preventive vaccine against HIV could work is a "prime boost" approach, consisting of two "prime" injections of a modified virus to get the body ready for antigens that are then delivered by the "boost" shots. The mosaic vaccine used here includes pieces of various HIV clades, or subtypes. This allows it to work globally, despite geographic differences in clades. The virus used for the prime shots (the vehicle for the antigens) is based on a flu virus vector, adenovirus 26 (Ad26).
The earlier APPROACH trial had tested seven vaccine variations and found Ad26 to be the best vector for the boost, as well. APPROACH was the human portion of two trials: First, vaccine efficacy was tested in non-human primates, and then its immunogenicity was studied in humans. The most promising variation was an Ad26 vector plus a high dose of the gp140 protein. This version was then used in TRAVERSE.
This time, variations on the vector were tested: a trivalent version, dubbed Ad26.Mos.HIV, designed to protect against three strains of HIV and a quadrivalent version, called Ad26.Mos4.HIV, that should work against four HIV viruses. The trivalent arm included 55 participants plus 11 in a placebo group, and the quadrivalent arm had 110 participants plus 22 in a placebo group, for a total of 198 people not living with HIV in the U.S. and Rwanda. Current results are 28 weeks into the trial, four weeks after the first boost injection. Nobody has seroconverted, and no deaths or study-related serious adverse events have been reported. Both vaccines were well tolerated, with complaints of minor to moderate injection site pain, fatigue, headache, and myalgia.
After the prime shots, all blood samples from vaccinated participants responded to the clade C matched protein in the boost -- i.e., all were "primed" for the boost. However, that response was twice as strong in the quadrivalent arm compared with the trivalent arm. The boost shot resulted in a fivefold greater immune response in the quadrivalent group and a threefold increase in the trivalent group. While the vaccine worked best against clade C virus, participants also developed antibodies against clades A and B. In addition, the quadrivalent version elicited a greater cellular immune response, a result of adding the Ad26.Mos2S.Env vector to the trivalent vaccine.
The efficacy of Ad26.Mos4.HIV will now be tested among young women in Southern Africa. Enrollment of 2,600 participants in that trial, Imbokodo, is expected to be completed in November 2018, and the study's primary endpoint should be reached by November 2020.