Single mRNA vaccine dose may be enough for those previously exposed to SARS-CoV-2

New research supports the notion that those who have recovered from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, may only need one dose of an mRNA vaccine to boost immunity. The findings showed no increase in circulating antibodies targeting the virus’s spike protein or antigen-specific memory B-cells after recovered individuals received their second dose.

The boost in immunity from the first mRNA vaccine could help with population immunity by allocating additional doses to high-risk groups, unexposed individuals, and countries in need of vaccines. To date, over 117.5 million cases of COVID-19 have been confirmed worldwide, resulting in over 2.6 million deaths.

These data advocate for only a single vaccine dose in individuals confirmed to have previously been infected with SARS-CoV2. It is important, however, to point out that our cohort consisted of individuals who were not hospitalized during their SARS-CoV2 infections, and it may be necessary to address this question in individuals who experienced more severe COVID-19.”

The study “Longitudinal Analysis Reveals Distinct Antibody and Memory B Cell Responses in SARS-CoV2 Naïve and Recovered Individuals Following mRNA Vaccination” is available as a preprint on the medRxiv* server, while the article undergoes peer review.

Study recruitment

The researchers recruited 11 people who recovered from coronavirus infection and 33 unexposed people from the University of Pennsylvania Health System to participate in the study. Every person received an mRNA vaccine (either Pfizer-BioNTech or Moderna). To study changes in immunity, the team collected blood samples before vaccination, 2 weeks after the first dose, the day the second mRNA dose was administered, and 1 week after the second dose.

Antibody differences after vaccination

Before vaccination, people who were never exposed to SARS-CoV-2 showed no antibodies specific for the coronavirus spike protein or the spike protein receptor-binding domain (RBD). However, there was a significant increase in SARS-CoV-2 specific antibodies after the first dose. Antibody levels increased further after the second dose.

In recovered individuals, there were also signs of immunity from SARS-CoV-2. Researchers found detectable levels of anti-spike and anti-RBD IgG antibody levels. This was further enhanced after the first mRNA vaccine dose.

However, the researchers found no significant changes to antibody levels when recovered individuals were given their booster shot. While the second dose did not enhance antibody levels, recovered individuals show similar immunity to those unexposed 1 week after their second shot.

Memory B cells differences

Similar to antibody data, people never exposed to SARS-CoV-2 showed negligible amounts of memory B cells at baseline compared to recovered individuals who showed approximately 0.15-0.8% of memory B cells. There were also memory B cells present that target the spike RBD.

The first vaccination increased memory B cell levels in both groups. In the non-exposed group, about 25-30% of spike-specific memory B cells were IgG^+, and about 40-50% were IgM⁺.

About 60-70% of spike-specific memory IgG⁺ B cells were observed in the recovered group before getting vaccinated. This was further enhanced by about 75%.

But the second dose only boosted memory B cells from individuals who were never exposed to SARS-CoV-2. More than 50% of IgG⁺ memory B cells increased after the second dose.

Based on these findings, the researchers suggest people who recovered from coronavirus infection do not benefit from a second mRNA dose.

In SARS-CoV2 naïve subjects, the fraction of the overall spike-specific memory B cell response that was focused on RBD increased over time, becoming equivalent to that observed in SARS-CoV2 recovered individuals after the second vaccine dose. Overall, these data indicate a qualitative benefit to the virus-specific memory B cell response following both doses of vaccine in SARS-CoV2 naïve individuals, and limited qualitative improvement following the first but not the second vaccine dose in SARS-CoV2 recovered subjects,” write the researchers.

While there were no significant associations between age and antibody levels, the researchers noted that older individuals in the study appeared to show weaker vaccine-induced antibody responses normalized after the second dose. However, this remains to be confirmed as only a few adults over the age of 50 participated.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.