Study: Those Who Recovered From COVID-19 May Receive Maximal Immunity From One Vaccine Dose

A study published in Science Immunology found that individuals who had COVID-19 and recovered had a robust antibody response after the first mRNA vaccine dose, but little immune benefit after the second dose. Those who did not have COVID-19 did not have a full immune response until after their second vaccine dose, according to the study.

The immune response to vaccination has 2 major outcomes: the production of antibodies providing rapid immunity and the creation of memory B cells, which assist in long-term immunity. According to the researchers, this is one of the first studies to uncover how memory B cell responses differ after vaccination in people who previously experienced infection compared to those who have not have COVID-19.

“Previous COVID-19 mRNA vaccine studies on vaccinated individuals have focused on antibodies more than memory B cells,” said E. John Wherry, PhD, chair of the department of systems pharmacology and translational therapeutics and director of the Penn Institute of Immunology in the Perelman School of Medicine at the University of Pennsylvania, in a press release. “Memory B cells are a strong predictor of future antibody responses, which is why it's vital to measure B cell responses to these vaccines. This effort to examine memory B cells is important for understanding long-term protection and the ability to respond to variants.”

The researchers followed 44 healthy individuals who received either the BioNTech/Pfizer or Moderna mRNA COVID-19 vaccine, 11 of whom had a prior COVID-19 infection. Blood samples were collected for deep immune analyses 4 times prior to and after vaccine doses.

According to the study, there were key differences in vaccine immune responses in COVID naïve individuals than those who had recovered from COVID-19. The findings suggest, based on strong antibody and memory B cell responses, those who recovered from COVID-19 may need only 1 dose of the vaccine to have a maximal immune response, according to the authors.

In contrast, 2 doses were required to demonstrate considerable antibody and memory B cell responses in the COVID naïve cohort. These findings were also reflected in an analysis of antibodies against the D614G mutation and the B.1.351 South African variant of COVID-19.

“We need to make sure people have the strongest memory B cell responses available,” Wherry said. “If circulating antibodies wane over time, our data suggests that durable memory B cells could provide a rapid source of protection against re-exposure to COVID-19, including variants.”

The study also examined vaccine-induced adverse effects (AEs) in relation to immune responses, finding that those who experienced systemic AEs after receiving a vaccine dose had stronger post-vaccination serum antibodies, but not memory B cells. According to the researchers, this suggests inflammation and AEs early after vaccination could signal stronger immune reactions, though more data are needed to confirm this, and all subjects of the study developed robust immunity.

The researchers are continuing larger studies, which are necessary to fully confirm whether a 1-dose regimen is appropriate in COVID-19-recovered individuals. Additionally, research is ongoing on the vaccine's effect on virus-specific T cell responses, another element of the body's immune response.


Penn study suggests those who had COVID-19 may only need one vaccine dose [news release]. EurekAlert; April 15, 2021. Accessed April 19, 2021.