People previously infected with SARS-CoV-2 may produce levels of antibodies against coronavirus disease (COVID-19) after one dose of the Pfizer–BioNTech messenger RNA (mRNA) vaccine that are equal to or higher than people not previously infected have after two doses, a new study finds.

Presented virtually March 9 at the Conference for Retroviruses and Opportunistic Infections (CROI), the results of the small, exploratory study also suggest that the immune responses in most patients previously infected with the pandemic virus did not improve further after a second dose of vaccine.

The study was led by researchers from NYU Grossman School of Medicine, under the auspices of NYU Langone’s Vaccine Center. The Pfizer vaccine had received an Emergency Use Authorization from the U.S. Food and Drug Administration on December 12, 2020, based on a clinical trial in which two doses of the vaccine were found to be safe and highly effective in 43,252 participants. Patients known to be previously infected were excluded from the original trial, as their immune response to the actual infection would have confused the measurement of their response to the vaccine, researchers say.

“Our findings support a hypothesis that SARS-CoV-2–experienced people may require only a single dose of mRNA vaccine,” says Mark J. Mulligan, MD, director of the Division of Infectious Diseases and Immunology and director of the Vaccine Center. “That said, our results would need to be borne out by larger studies before they influenced current policy, which is that patients receive the evidence-based, two-shot regimen. Should the final data support it, the goal would be to make more doses available quicker if a subset of patients didn’t need a second shot.”

Between December 14, 2020, and March 7, 2021, more than 90 million doses of the study vaccine were administered, according to the Centers for Disease Control and Prevention, but just 17.7 percent of the U.S. population had received one or more doses of a vaccine.

Study Details

Vaccines safely mimic actual infections, which teaches the immune system to be ready for a future encounter, researchers say. The Pfizer vaccine is based on RNA, or ribonucleic acid, which serves as the primary genetic material instead of DNA for the pandemic coronavirus. The vaccine contains viral mRNA encoding the “spike proteins” used by SARS-CoV-2 to attach to proteins on human cell surfaces, the first step in invading the cells in which it multiplies.

Including the spikes in vaccines has made proteins required for viral ability to infect visible to the human immune system, say the study authors. Once injected into the arm muscle, the spike protein is made and triggers the production of antibodies, immune proteins that specifically glom onto this viral target protein, disabling it and tagging it for removal from the body.

In the new study, people that previously had COVID-19 infection and who received a single dose of mRNA vaccine produced high levels of “neutralizing” antibodies—those capable of defending cells from the virus and of blocking its biological effects—at 6 to 14 days after the shot that were similar to, or higher than, those in SARS-CoV-2–naive people who had received 2 doses.

Specifically, specimens were collected from 33 participants before and 6 to 14 days after doses 1 and 2. Thirty-two adults received the Pfizer vaccine, and one the Moderna mRNA vaccine. Fourteen of 33 had a history of COVID-19 (median age 41, 71 percent female, range of severity), while 19 had not been exposed to SARS-CoV-2.

To compare immune responses after one and two doses of vaccine, the research team used a well-known technology, enzyme-linked immunosorbent assay (ELISA), which had been tailored in recent months to find the number of useful antibodies in a person’s blood by presenting to it a sample of the spike protein from the COVID-19 virus. Those antibodies that can attach to the spike do so, while those that cannot are washed away.

The authors also used live-virus microneutralization (MN) against the original SARS-CoV-2 U.S. pandemic strain, a gold standard, high-speed test that indicates whether antibodies created by a vaccine are present and how well antibodies in a sample of blood sera neutralize a virus (for example, the lowest concentration of antibodies to still have an antiviral effect).

Along with Dr. Mulligan, authors of the study from NYU Grossman School of Medicine were Marie Samanovic, Amber Cornelius, Trishala Karmacharya, Jimmy Wilson, Sophie Gray-Gaillard, Joseph Allen, Sara Hyman, and Ramin Herati, of the NYU Infectious Diseases with Public Health Importance (IDPHI) Study Team. The study was funded in part by the National Institutes of Health.

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