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Boosters increase protection over full vaccine dose

Protection may last longer after COVID-19 booster than after second vaccine dose

CHICAGO --- A new Northwestern University study on the effectiveness of COVID-19 boosters shows they generate a stronger antibody response than after a full two-dose vaccination.

These are the first findings showing the antibody response to booster doses is much larger than the response after the second vaccine dose and even higher than the responses among people who had natural infections as well as full vaccination.  

The study was done in a younger, healthy adult population, with a median age of 43, recruited from the Chicagoland area. Much of the previous information on COVID-19 booster efficacy had been from Israel, with the majority of data reported evaluating the adult population over age 65.

The study also suggests protection after booster may last longer than after the second vaccine dose. 

“Because these antibody levels are so robust, the booster could potentially give us protection for a longer duration than what we saw for two doses of the vaccine,” said co-corresponding author Alexis Demonbreun, an assistant professor of pharmacology at Northwestern University Feinberg School of Medicine.

Key findings:

  • Nine months after individuals had two doses of the Pfizer or Moderna vaccines, their neutralizing antibody levels to SARS-CoV-2 decreased about 10-fold. 
  • After the COVID-19 booster, protective antibody levels climbed 25-fold, five-fold higher than after two doses of the vaccine
  • Booster antibodies were 50-fold higher than those from natural infection

“The findings are relevant to anyone who is vaccinated and considering a booster,” said co-corresponding author Thomas McDade, professor of anthropology in the Weinberg College of Arts and Sciences and a faculty fellow with the University’s Institute for Policy Research. “We know the mRNA vaccines provide a high level of protection against serious cases of COVID-19 that lead to hospitalization or death. But immunity wanes over time — particularly levels of antibodies that help prevent infection — and we are seeing higher rates of breakthrough infections as a result, particularly in combination with the rise of the more infectious Delta variant.” 

The study shows booster doses generate a high level of neutralizing antibodies against the Delta variant, which should provide a high level of immune protection, scientists said. However, the neutralization response was even higher against the original version of the virus because that is the version the vaccine was designed around.  

The Northwestern research team has been evaluating antibody responses from the start of the pandemic and has published multiple studies following levels of antibodies from natural infection and after dose one and dose two of the vaccines. Initial studies sampled hundreds of blood samples; later studies sampled nearly 8,000. The trends have been consistent regardless of the number of samples, scientists said. The current study examined 33 paired samples. 

“We really do think the robust effect we are observing after booster vaccination in this small cohort will be mirrored in much larger populations,” Demonbreun said.

The study was published Nov. 21 on medRxiv, a preprint server for health sciences, due to the timeliness and importance of the findings. It has not yet been peer-reviewed and should be considered a preliminary finding.

For the study, participants completed online surveys regarding COVID-19 viral history and vaccination status. Finger-stick dried blood spot samples were self-collected prior to booster administration and six to 10 days after receiving a mRNA booster vaccine. Neutralizing antibody concentration and activity were then measured from the paired samples.

The Northwestern team will continue to evaluate antibody levels over time and monitor breakthrough infections to assess waning immunity.

The research was supported by the National Science Foundation grant 2035114, the National Institutes of Health, National Center for Advancing Translational Sciences grant 3UL1TR001422-06S4 and Northwestern University Office of Research.