Wall Street's main indexes fell on Tuesday after a four-day winning streak as a pause in Johnson & Johnson's COVID-19 vaccine trials spurred concerns about a full economic rebound from the coronavirus-led downturn.

Johnson & Johnson raised its annual profit forecast, but its shares dropped 1.2 percent as it suspended clinical trials following an unexplained illness in a study participant, possibly delaying one of the most closely watched efforts to contain the global pandemic.

Some of the worst-hit companies due to the pandemic - cruise line operators Carnival Corp, Norwegian Cruise Line Holdings and hotel operator Wynn Resorts Ltd - were among the top losers on the S&P 500.

"It reminds those betting on a vaccine that it's probably not as clear cut that it's just on the horizon as the administration makes it to be," said Rick Meckler, a partner at Cherry Lane Investments, a family investment office in New Vernon, New Jersey.

Adding to the negative tone, U.S. House Speaker Nancy Pelosi rejected President Donald Trump's latest offer on COVID-19 stimulus, in the latest sign that a bipartisan deal on coronavirus relief remains unlikely ahead of the November election.

Hopes of more U.S. fiscal stimulus and a rally in technology heavyweights led stocks higher on Monday, bringing the benchmark S&P 500 and the tech-heavy Nasdaq within 2% of their record highs hit in September after a pullback last month.

Apple Inc gave up early gains to fall 1.9% ahead of a virtual event starting 1 p.m. ET (1700 GMT) where it is widely expected to unveil four new iPhones.

Shares of Amazon.com Inc, which have already surged 86% this year, added 0.2% as it began 48 hours of promotions as part of "Prime Day" in an early start to the holiday shopping season.

Kicking off third-quarter earnings season, JPMorgan Chase & Co and Citigroup surpassed analyst estimates for quarterly profit on a surge in trading revenue. However, their shares fell 0.3% and 1.6%, respectively.

Bank stocks slipped 0.6 percent. The index has widely underperformed the broader market in 2020 and analysts expect the sector's earnings to take years to make a full recovery as interest rates remain near record lows.

Overall, analysts expect third-quarter earnings for S&P 500 firms to slide 20.7 percent from a year earlier, smaller than a 31 percent tumble in the prior quarter.

At 9:54 a.m. ET, the Dow Jones Industrial Average was down 109.40 points, or 0.38 percent, at 28,728.12, the S&P 500 was down 12.27 points, or 0.35 percent, at 3,521.95, and the Nasdaq Composite was down 30.51 points, or 0.26 percent, at 11,845.75.

Walt Disney Co jumped 3.5 percent as it restructured its media and entertainment businesses to accelerate growth of Disney+ and other streaming services.

The world's largest asset manager BlackRock Inc rose 3.7 percent after reporting better than expected quarterly profit as the recovery rally in global financial markets boosted asset values and pulled in more investor funds.

Declining issues outnumbered advancers for a 2.54-to-1 ratio on the NYSE and for a 1.98-to-1 ratio on the Nasdaq.

The S&P index recorded 23 new 52-week highs and no new low, while the Nasdaq recorded 41 new highs and six new lows.