Another large clinical trial has been halted after Johnson & Johnson’s experimental HIV vaccine was found to be safe but not effective against HIV. The Phase III Mosaico study enrolled 3,900 cisgender gay and bisexual men and transgender women in North and South America and Europe. Participants received four doses of a vaccine called Ad26.Mos4.HIV that uses an adenovirus vector to deliver antigens from multiple HIV strains plus two doses of a second vaccine containing gp140 proteins. An interim data review found that the number of people who acquired HIV was statistically equivalent in the vaccine and placebo groups. The results were not surprising, as a par--allel trial dubbed Imbokodo was halted in 2021 after interim results showed that a similar vaccine regimen did not protect young women in Africa. The news adds to a long string of disappointments in HIV vaccine research. Mosaico was the last large trial testing a traditional vaccine for HIV prevention. Most experts now think more sophisticated approaches will be needed.