Prince Harry delivered a passionate speech in his first appearance since Prince Philip's funeral at the Vax Live concert in California - but pregnant wife Meghan was notably absent.
The Duke and Duchess of Sussex are campaign chairs for Global Citizen's Covid-19 vaccination campaign and had been billed to take the stage together to "deliver an important global message for vaccine equity during the event".
Instead, Harry went solo, receiving a rock-star welcome as he addressed the crowd of thousands of vaccinated frontline workers during the taping of the star-studding concert SoFi Stadium in Los Angeles.
"We are at a defining moment in the global fight against Covid-19," said the 36-year-old, who was given a standing ovation as he appeared alongside Jennifer Lopez, Foo Fighters and Sean Penn at the "concert to reunite the world".
He said the concert, which will be broadcast next weekend, was a celebration of the "frontline heroes" in the crowd and around the world.
"You spent the last year battling courageously and selflessly to protect us all," he said, before referencing the "service" that is so often referenced by the royals.
"You served and sacrificed, put yourselves in harm's way and with bravery knowing the costs. We owe you an incredible depth of gratitude, thank you."
The Duke of Sussex said the virus "does not respect borders" and that "access to the vaccine cannot be determined by geography", as he made his first appearance at a public event since moving to California last year.
"Tonight, we stand in solidarity with the millions of families across India, who are battling a devastating second wave," he added.
"We're also coming together because this pandemic cannot end unless we act collectively with an unprecedented commitment to our shared humanity."
He called for the vaccine to be distributed "to everyone, everywhere", adding that "we cannot rest or truly recover until there is fair distribution to every corner of the world."
Dressed in a blue shirt and dark pants, the prince also called vaccine disinformation a "humanitarian crisis" that is "getting worse".
Host Selena Gomez said the concert was "the best award show of the year" and said she "geeked out" when she saw the line-up of celebrity guests and performers.
The singer called for "doses and dollars" for the world's poorest countries, as the United States and many Western countries emerge from lockdown as their vaccination programmes roll out at speed.
JLo wore a glittering pink dress as she told fans she had been forced to spend Christmas without her mother for the first time due to the pandemic. She then brought her mum on to the stage for a touching performance of Sweet Caroline.
The Foo Fighters performed Back in Black with AC/DC star Brian Johnson. Frontman Dave Grohl told the crowd — many wearing uniform — "we ain't out of the woods yet", adding "let's work as hard as we can to make sure we can do this" every night.
Actors Ben Affleck and Olivia Munn and late-night host Jimmy Kimmel were also among the guest stars.
President Joe Biden and First Lady Dr Jill Biden appeared in a video address, with Mr Biden saying the US was "working with leaders around the world to share more vaccines and boost production to make sure every country has the vaccines they need."
Pope Francis also appeared by video, saying, "I beg you not to forget the most vulnerable" and calling for "a spirit of justice" to ensure "true universal access to vaccines, and a temporary suspension of intellectual property rights."
Bollywood star Amitabh Bachchan shared an urgent plea from India, where cases continue to soar, saying: "My country India is battling with the sudden surge of the second wave of Covid-19. As a global citizen I appeal to all global citizens to rise up, speak to your governments, your pharmaceutical companies, and ask them to donate, to give, to extend a helping hand to the public that needs it the most. Every effort counts."
Other leaders including French President Emmanuel Macron, Canadian Prime Minister Justin Trudeau and European Commission President Ursula von der Leyen also appeared by video link.
Global Citizen, the advocacy group behind Sunday night's event, announced that it had raised US$53.8 million for vaccine procurement, medical tools and supplies.
Corporate and philanthropic partners have committed to donating US$39.5 million to vaccine-sharing programme COVAX, which is co-led by the World Health Organisation, the Coalition for Epidemic Preparedness Innovations (CEPI) and Gavi, the Vaccine Alliance.
Gavi will match at least US$11.75 million for a total of US$51.25 million to help procure nearly 10.3 million vaccine doses, exceeding the 10 million target.
Donors included Mastercard at US$25 million, Cisco at US$5 million and Procter & Gamble at US$5 million, with Spotify contributing US$500,000 to vaccines and US$500,000 to medical supplies.
More announcements will be made during the YouTube broadcast at 8pm Saturday May 8 local time.
The campaign is also calling on governments to begin sharing vaccine doses immediately, and for pharmaceutical companies such as Moderna to urgently provide millions of doses to the poorest nations at cost pricing.
"Critically, we need to see the US and the UK step up and start sharing additional doses, and we need pharmaceutical companies such as Moderna to urgently provide millions of doses to COVAX for the poorest nations at nonprofit prices," said Global Citizen's Melbourne-born CEO Hugh Evans.
The concert is part of Global Citizen's 2021 Recovery Plan for the World, a year-long campaign to help end Covid-19 for all by raising money for the World Health Organisation's vaccine-sharing programme COVAX.
"Over the past year, our world has experienced pain, loss, and struggle - together," concert campaign chairs Harry and Meghan, 39, said in a statement on their website. "Now we need to recover and heal - together. We can't leave anybody behind. We will all benefit, we will all be safer, when everyone everywhere has equal access to the vaccine. We must pursue equitable vaccine distribution, and in that, restore faith in our common humanity. This mission couldn't be more critical or important."