But one day in 2009, while Mascola was sitting in the lab’s break room about to eat a sandwich, one of his scientists jumped towards him with a big smile on his face: They found the glow they were looking for.
This antibody came from a man known as Donor 45. Doria-Rose, who met with the study participants when they came for their regular exams, said Donor 45 was a gay black man extremely deprived of his 60 years in the area of Washington, DC. They dubbed the VRC01 antibody – the first from the Vaccine Research Center.
It took almost a decade to develop a drug from that antibody and start a clinical trial to make sure it was safe and effective. Other HIV researchers, taking different paths, have discovered antiretroviral drugs – the famous “triple cocktail” – that effectively treat and prevent HIV infections by interfering with the virus’s ability to make copies of itself. The crisis is not over. People still contracted HIV, but with antiretrovirals they could lead normal lives. With the expansion of access to these drugs, the effort to use antibodies to make HIV drugs has become less urgent. It all started, a clinical trial was started, but not so many people were paying much attention.
And then came Covid-19. That day in January 2020, Mascola immediately saw that everything he and his colleagues learned from studying HIV antibodies could be mobilized to treat the new pathogen. It would be “the culmination of a lifetime’s work,” he says.
Mascola is a restrained guy. It communicates with economics. “When he puts an exclamation point in an email, you know he did something phenomenal!” Doria-Rose wrote to me. So when he came to her office, they got right to the point. Doria-Rose started asking team members to turn on the cell sorting machines and fill the small cans of muffins and the glowing engineering test cells. They reviewed their work schedules and went all in.
Even before you were born, their immune system started to produce antibodies to fight potential pathogens. They are surprisingly diverse: the average person has billions of B cells that can produce anywhere from 9 to 17 million different antibodies. The antibody molecules are Y-shaped and their tips have corners that can attach to specific viruses or bacteria. When this connection occurs, the antibodies prevent invaders from attaching themselves to healthy cells and take them away. What is truly ingenious, however, is not only that an antibody can seek its enemy for destruction, but that the act of fixing on the pathogen is also a signal for the immune system to do more in that particular way. Even an antibody can summon troops, allowing your immune system to wage war against an invading army.
Unfortunately, when an entirely new pathogen like HIV or the new coronavirus emerges, a very compatible form is rare, even in our enormous, preexisting natural antibody repertoire. Vaccines, which usually consist of a weakened virus or fragments of a virus, train the body to develop a blocking antibody – one that binds and neutralizes the real pathogen when we find it in the world. This is known as active immunity. The body’s immune system undergoes basic training and emerges with adequate combat strength. In contrast, antibody therapies like the one Mascola worked for HIV provide passive immunity: an army of mercenaries is introduced into the body to temporarily do the job for you.
The discovery of passive immunity dates back to the late 19th century, when Emil Behring, a German scientist with sad, half-closed eyes and a trimmed beard, began to inject animal blood into 220 children. All the children contracted diphtheria, a horrible disease that slowly suffocated its victims. Behring had been trying to treat the disease, experimenting with rabbits, guinea pigs, goats and horses, giving infected animals the blood of the recovered. He didn’t know why, but the sick animals got better. So he gave children the blood of animals exposed to diphtheria and, in 1894, published the results: About twice as many children as they would normally be expected to survive actually survived. Behring’s “serotherapy” approach was considered such a success that he later received the first Nobel Prize in Physiology or Medicine.