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This phase 1 placebo-controlled study assessed safety and immunogenicity of two-dose regimens of Ad26.ZEBOV (Ad26) and MVA-BN-Filo (MVA) vaccines with booster vaccination at Day 360. Healthy US adults (N = 164) randomized into 10 groups received saline placebo, standard or high doses of Ad26 or MVA in two-dose regimens in 7-, 14-, 28-, or 56-day intervals; eight groups received booster Ad26 or MVA vaccinations on Day 360. Participants reported solicited and unsolicited reactogenicity; we measured IgG binding, neutralizing antibodies an