Winnie Jiang, Staff Illustrator

Yale scientists published a novel study demonstrating that messenger RNA vaccines, such as Pfizer’s and Moderna’s, cultivate a vigorous immune response to most variants of SARS-CoV-2.

A Yale research team led by Akiko Iwasaki, professor of epidemiology and immunobiology at the Yale School of Medicine, and Nathan Grubaugh, associate professor of epidemiology at Yale School of Public Health, published the study on Oct. 11 in the journal Nature. It showed that mRNA vaccines, particularly coupled with prior exposure to COVID-19, seem to be effective against most strains of SARS-CoV-2. This has led researchers to believe that a booster shot is essential to fighting against most COVID-19 strains.

“[This is] the first large-scale study where we are using real viruses that are circulating in our communities to understand the impact of vaccines,” Grubaugh said.

The team enrolled a cohort of 40 health care workers from November 2020 to January 2021 prior to being vaccinated with the Pfizer or Moderna vaccine. Researchers took 198 blood samples from the cohort. Subsequently, investigators separated the cohort into two groups: a group of individuals infected with COVID-19 prior to vaccination and a group of individuals who were not previously infected prior to vaccination. The team then exposed the blood samples from each group to 16 different variants of SARS-CoV-2.

Although blood samples showed that both vaccinated groups were able to neutralize infection from all variants, the previously infected group, collectively, had a more robust neutralization response. 

“Some people produced very large amounts of neutralizing antibodies … and others didn’t have any neutralizing antibodies at all, even after the vaccination,” Grubaugh said. 

Iwasaki added that there were only two individuals who did not produce neutralizing antibodies, but those individuals did “generate virus-binding antibodies.” 

This published study is unique in that it is the first to utilize circulating authentic viruses from the community instead of pseudo-viruses that many other labs have used, according to Chantal Vogels, associate research scientist of epidemiology at the School of Public Health.

Vogels added that in the study, investigators did not just introduce a single mutation but instead used a “full-length infection virus.” 

The study also demonstrated variations in antibody production between individuals, which underscores the importance of booster shots. 

“[Boosters] raise everybody’s immunity so that they can catch some of the people who may not have had a strong immunity from the first exposures,” Grubaugh explained.

The authors also addressed the Delta variant, the variant that has caused breakthrough cases in the U.S., and suggested that infection is “more likely associated with its high transmissibility.”

The Grubaugh lab is surveilling circulating strains in the state. With these surveillance programs in place, researchers and public health experts can see which variants are on an upward trend and can respond quicker. Per the Grubaugh lab’s most recent surveillance, from Oct. 14, 99.7 percent of sequenced cases in Connecticut were caused by the Delta variant.

“All that we sequence really is built [in terms of infrastructure to combat future possible variants]. … Delta is well neutralized after vaccination,” Vogels said. 

There are some limitations in the study, particularly with its cohort’s design. The discussion section of the study notes that the cohort is predominantly made up of white women. Research on the effectiveness of mRNA vaccines on SARS-CoV-2 variants with a more demographically diverse cohort is critical for future studies, the study reads.

“Most of them were white women because this was a cohort of health care workers … and the study was actually designed to help understand how we could protect the health care workers at Yale New Haven Hospital in general,” Albert Ko, professor of epidemiology at the School of Public Health and professor of infectious diseases at the medical school, told the News. 

Ko added that many other groups were looking at the issue in a “much broader” light, and that the study was not meant to do that specifically. 

Iwasaki noted that her team and others are conducting studies with more diversity among subjects. 

“[My team is working on] multiple other studies with a more diverse cohort [from] the Dominican Republic, China, and Brazil … [places with] heterogeneous group[s] of people that have gotten different sets of vaccines,” Iwasaki said. 

Results from those studies have yet to be published. 

Though the study sees boosters as a useful protective factor against possible emerging variants, Iwasaki and Vogels said that there are ethical implications when many low-to-middle income countries have little to no access to initial doses. 

Vogels advocates for vaccine equity and said “at the population level,” it is “more beneficial to make sure that people get the first and second shots before we start getting boosters.” Iwasaki added that “the first goal is to vaccinate the entire world” and hopes that health policymakers ensure equitable distribution of vaccines. 

Flu season will exacerbate COVID-19, as it has historically increased hospitalizations during the winter months. Public health experts explained that getting the flu shot is just as important as getting a booster once eligible in order to mitigate infection rates and prevent community spread of COVID-19 and the flu. 

Ko warned of a worrisome influenza season. 

“Before COVID-19, each year we’d go into a hospital surge crisis, all the hospitals in Connecticut including Yale New Haven Hospital because of influenza,” Ko said. “So if we get a really bad influenza epidemic, it’s going to certainly … put another stressor … if we also have a concomitant COVID-19 epidemic … so that’s why influenza vaccination is going to be important,” Ko said. 

Despite flu season having low prevalence last year — likely due to social distancing policies — Iwasaki suggested remaining vigilant, and said that just because people may have gotten the COVID-19 vaccine, they are not protected from other viruses like the flu. 

The study was a collaboration between multiple labs at the School of Public Health and the medical school.