UCSF Grand Rounds: The Delta variant and vaccine efficacy, durability and boosters

Back by popular demand (unfortunately), UCSF’s Covid Grand Rounds returned for a special edition Thursday to discuss the current Covid-19 surge and the vaccines meant to stop it. The city now has around 250 cases per day, compared to 10 per day on June 1, and the Delta variant comprises the vast majority of new cases. 

Delta, immunology and vaccines 

“At this point, you’re either vaccinated or you’re going to catch Delta,” said the first guest, Dr. Shane Crotty, professor at the La Jolla Institute for Immunology. Crotty got into the nitty gritty of how the mRNA vaccines, made by Pfizer and Moderna, are faring in the four categories important to durability and efficacy: antibodies, memory B cells, CD4+ T cells, and CD8+ T cells. 

For the Moderna vaccine, covid antibodies are present six months beyond the second dose, though there is about a five-fold decline from the peak amount, Crotty said. Antibodies are specialized proteins in the body that bind to invaders (such as viruses) and inactivate them, and can also mark them for destruction by other parts of the immune system.

Discussing a preprint study from the Center for Infectious Diseases and Vaccine Research at the La Jolla Institute for Immunology, Crotty also said that Moderna recipients have stable CD4+ T cell counts, without much decline, six months after their second dose. CD4+ T cells release small proteins that act as chemical signals to activate other immune cells that neutralize invaders. 

Though there is some uncertainty regarding CD8+ T cells, which directly kill infected cells, both Moderna and Pfizer vaccines generate them. 

Regarding memory B cells, there is no data on whether they’re present six months after a second vaccine dose, but studies indicate they are present two months after vaccination, Crotty said. Memory B cells “remember” invaders long after they have been eliminated, activating a fast immune response when the body is re-exposed to the same invader. Crotty predicts memory B cells from mRNA vaccines are “quite robust and long-lasting.” 

Moving on to efficacy, Crotty said that phase 3 clinical trial results for the Pfizer and Moderna vaccines showed 91 and 93 percent efficacy overall, with Pfizer’s efficacy dropping from 95 percent after one month to 84 percent after six months. 

“The vaccines are doing quite well at generating immune responses that are good at targeting variants,” Crotty said. Delta has a modest to moderate degree of antibody escape and no obvious escape from T cells. Memory B cells have also been shown to have “an excellent repertoire” against Delta, Crotty said.

The New England Journal reported that Pfizer is 88 percent effective against symptomatic infection with the Delta variant. However, not all scientists agree, with an Israeli study reporting only 39 percent efficacy against infection. Though the level of protection vaccines provide against Delta is uncertain, the study did demonstrate that Pfizer reduces hospitalizations and deaths.

State of the pandemic and boosters

Globally, there have been over 200 million covid infections and over four million deaths, said Dr. Carlos Del Rio, executive associate dean at the Emory School of Medicine. “I try to remind people that this pandemic is not over, it’s accelerating.” There have been more covid deaths in 2021 than all of 2020. 

Del Rio cautioned against saying things like ‘Once we reach a peak, it’s going to come down very rapidly and go back to where we were before.’” The United States, he said, is driving the pandemic globally, and is where cases are accelerating the fastest. Some 70 percent of U.S. counties have “high transmission,” and another 18 percent have “substantial transmission.” If Florida was its own country, it would have the highest case rate in the world.

Covid is spreading faster in places with low vaccination rates. The good news, Del Rio said, is that 70 percent of adults in the United States have had at least one vaccine dose, but the bad news is that “one dose doesn’t do much against Delta.”

The R0 (pronounced “R naught”) measures the expected number of cases directly generated by one infected individual. Though covid originally had an R0 value around 2.5, the Delta variant’s R0 is somewhere between 5 and 8. A change of this size is unprecedented and has large ramifications.

Herd immunity at R0=2.5 is 60 percent and, after 10 cycles of infection, leads to 9,536 cases. At R0=6, herd immunity is 84 percent — a number Del Rio believes we will never reach nationwide — and leads to 60,466,176 cases. Even in places like San Francisco, where 70 percent of the population is fully vaccinated, herd immunity will likely be impossible because models rely on vaccines with 100 percent efficacy, he said.  

Breakthrough infections are inevitable, Del Rio said, but the risk of getting covid is eight times lower if one is vaccinated, and 25 times lower for hospitalizations and death. The single most important thing people 12 and over can do is get vaccinated. The second is to wear face coverings. Though vaccinated individuals can transmit the virus, this is likely for a shorter period of time, and therefore their contribution to transmission is much lower, Del Rio said. 

Crotty and Del Rio agreed that right now, most people do not need booster shots. They did suggest that those with the Johnson & Johnson vaccine get another dose of an mRNA vaccine. Del Rio believes one reason why the Food and Drug Administration may be delaying the approval of the vaccines is so they do not become available for sale commercially, especially when vaccination rates globally are so poor. 

Both doctors are wearing masks indoors and transitioning back to remote meetings. As for what life will look like six to 12 months from now, Crotty is uncertain. 

“Maybe the virus doesn’t have too many tricks left, but it’s hard to bet against that at this point,” he said.

Del Rio reminded viewers that pandemics end. “A lot is going to depend on, really, how our society behaves,” he said. He is worried about covid becoming a disease of pandemic-poor and underrepresented communities long-term.

“We need to really focus on health equity, not only globally, but locally. And if we don’t do that, I think the pandemic is going to hang around for a lot longer than we actually want.” 

See our previous Grand Rounds coverage here. Grand Rounds will return Thursday, Sept. 9, and continue on the first Thursday of every month for the foreseeable future, though “hopefully not forever,” said Wachter.