The FTSE-100 dropped into the red despite positive early results from the University of Oxford Covid-19 vaccine trials which helped to drive AstraZeneca higher.
Traders remained downbeat in the face of the update, having already priced in positive results following reports that it would show progress at the end of last week.
London's top flight closed 28.78 points lower at 6,261.52 at the end of trading on Monday.
Connor Campbell, financial analyst at Spreadex, said: "Monday's uneven trading came in the face of a remarkably positive update from the Oxford vaccine trials, with the university stating the injection appears safe, and triggers an immune response in human patients."
AstraZeneca closed firmly in the green but was significantly below intra-day highs as traders quickly sold off stock following an initial jump.
It also said that current results focus on the immune response measured in the laboratory, and further testing is needed to confirm whether the vaccine effectively protects against infection.
The pharmaceutical firm closed 133p higher at 9,320p as a result.
The major European markets were more positive, as they rebounded in confidence towards the end of the session, buoyed by weakness in the euro.
The German Dax increased by 0.99%, while the French Cac moved 0.47% higher.
Across the Atlantic, the Dow Jones dropped on the opening bell as trading restarted after another weekend of record-breaking daily increases in new coronavirus cases across the US.
Meanwhile, sterling pushed higher as it took advantage of weakness in the dollar and the euro.
The pound rose 0.67% versus the US dollar at 1.265 and was up 0.44% against the euro at 1.106.
Retail and leisure firms largely drifted lower during the session as traders remain cautious about the impact of the virus on consumer spending.
In company news, Marks & Spencer nudged lower after the high street firm confirmed it has put 950 roles at risk after accelerating its transformation plan.
M&S said the proposals, which will affect roles in the company's head office, property and store management areas, will help move the company to "a leaner, faster retail management structure". Shares closed down 0.22p at 98.62p.
GlaxoSmithKline slipped after it announced plans to put £130 million into German vaccine firm CureVac for 10% of the business. Shares closed 11.8p lower at 1,648.1p.
Guarantor lender Amigo Loans plunged by 2.78p to 6.92p after it told investors that complaints cost the business £126.8 million over the past year.
The price of oil moved marginally higher despite concerns that the health crisis will curtail demand.
The price of a barrel of Brent crude oil increased by 0.12 to 43.14 US dollars.
The biggest risers on the FTSE 100 were Aveva, up 113p at 4,194p, Polymetal, up 41p at 1,655p, Rightmove, up 12.2p at 586.4p, and Hargreaves Lansdown, up 29p at 1,589p.
The biggest fallers of the day were IAG, down 7.9p at 211p, ITV, down 2.22p at 64.6p, BAT, down 79.5p at 2,705.5p, and Prudential, down 34.5p at 1,218p.
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