Alberto Contador attempted a twin attack with Nibali in the final 3km to dart 10 seconds ahead of the red jersey group, but could not last and finished six seconds behind Froome, in seventh.
Lopez, who claimed his first Grand Tour win in Wednesday's 11th stage, broke clear in the final five kilometres to win the mountainous 129.4km climb from Alcala la Real to the Sierra Nevada at 2,500m above sea level in 3hr 34min 51sec. "Now I'm just so happy, not because I won, but for my teammates", Majka said.
Nibali did gain four bonus seconds on Froome, but the Team Sky rider still heads the GC by 55 seconds from his Bahrain-Merida rival.
Miguel Angel Lopez (Astana) joined him before going on alone for his second stage win of the race.
Race favorite Froome had a mechanical issue with around eight km remaining in the 160.1 km (99 miles) stage from Motril to Antequera Los Dolmones and was forced to change bikes.
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Ostapenko, the French Open champion, won 12 of 14 points played inside to wrap up a 6-2, 1-6, 6-1. Open is known for loud, boisterous crowd and the roof only makes the crowd sound even louder.
On one of the brief sections of respite, Stage 5 victor Alexey Lutsenko attacked and slipped the field, although he did the same with his gears at just the wrong time, whilst the main group was now about 30 thanks to the relentless work on the front of Quick-Step's aforementioned riders, with a split between the two sections of the peloton. "The Vuelta is not over and we will go forward step by step". After my first victory I was keeping fresh to try again today.
The three-time Vuelta victor, riding in his last race before retirement, launched his attack early with 26.5km remaining in the 129.4km stage 15. I think it was the right decision, we've kept the energy for the stage tomorrow [Sunday], " responded Froome.
Russia's Ilnur Zakarin attacked in the final kilometre to take second, 36 seconds back, and also climb ahead of Wilco Kelderman into third overall.
"I knew that at 10k I need to go at full gas like a time trial", said Majka.