A second dose of Pfizer-BioNTech COVID-19 vaccine may not benefit previously infected individuals

Researcher NYU Grossman School of Medicine In the second vaccination with Pfizer-BioNTech BNT162b2 vaccine, the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

In a study assessing the immune response to the Pfizer-BioNTech vaccine, Ramin Herati et al. Strongly vaccinated individuals who were not previously infected with SARS-CoV-2 (SARS-CoV-2-naive) twice. A humoral (antibody) reaction was observed.

However, participants who experienced SARS-CoV-2 showed a strong humoral response to the first dose, but a suppressed response to the second dose.

In fact, individuals who experienced SARS-CoV-2 had lower circulating levels of antigen-specific antibody-secreting cells (ASCs) after the second dose than after the first dose.

“These data can highlight important gaps in our knowledge and have a significant impact on how these vaccines should be used to prevent COVID-19,” Herati and his team said. Is writing.

The preprinted version of the research treatise is medRxiv* The server while the article is being peer reviewed.

SARS-CoV-2 infection causes an important antibody response

The SARS-COV-2 infection process is mediated by a surface structure called Spike proteinIt binds to the host cell receptor angiotensin converting enzyme 2 (ACE2) via the receptor binding domain (RBD).

Peplomer proteins are composed of two subunits. Subunit 1 (S1) contains RBD, which binds to ACE2 via a receptor binding motif (RBM), which allows the viral membrane to fuse with the host cell. To.

After natural infection, antibodies targeting spike RBD are thought to account for over 90% of SARS-CoV-2 neutralizing activity.

Studies have shown that existing immunity to SARS-CoV-2 is associated with protection against reinfection in humans and animals.

Antigen-specific B cells have diminished circulation one week after the second vaccination of individuals who have experienced SARS-CoV-2. A. Study the schematic. B. S1 antibody titers were evaluated for subjects with SARS-CoV-2 experience (purple) and SARS-CoV-2 inexperienced (yellow) subjects. The connected lines show repeated measurements of the same subject. C. Neutralizing antibody Titers were assessed using an in vitro neutralization assay. DE. ELI Spot assay shown for representative SARS-CoV-2-naive (D) or SARS-CoV-2 experienced (E) subjects one week after each dose of vaccine. FH. Summary statistics shown for the ELI Spot assay. For each panel, S1 (left), S2 (center), or RBD (right) antigen It is shown for IgG one week after the first dose (F) or second dose (G), or IgA one week after the first dose (H) or second dose (I). JL. ELI Spot data shown for subjects with SARS-CoV-2-naive (left) or SARS-CoV-2 experience (right) with S1 (J), S2 (K), or RBD (L). The connected lines show repeated measurements from the same subject.

Recently approved vaccines are based on spike proteins

Both the Pfizer-BioNTech vaccine and the Moderna vaccine, which have recently been approved by the FDA for emergency use against SARS-CoV-2, are mRNA-based vaccines that encode regions of peplomer.

These novel mRNA vaccines elicit a strong humoral response to SARS-CoV-2 and have been shown to be 94% effective in disease prevention in large clinical trials, leading to the COVID-19 pandemic. It is considered important to end it.

However, efficacy studies excluded individuals who were pre-diagnosed with COVID-19 and focused only on individuals who had not previously been exposed to SARS-CoV-2.

“As a result, little is known about the immune response of individuals who have experienced SARS-CoV-2. This is a situation that affects hundreds of millions of people around the world,” Herati et al.

“In fact, more research is needed to fully understand the breadth and quality of the immune response to these vaccines.”

What did the researchers do?

The team evaluated the immune response of 32 patients (ages 24-62) who received the Pfizer-BioNTech BNT162b2 vaccine as a double-dose regimen.

Thirteen of the participants (median 41 years) were previously infected with SARS-CoV-2 and the remaining 19 (median 39 years) were inexperienced with SARS-CoV-2.

All participants evaluated the immune response approximately at intervals before and after each dose of vaccine.

What did the study find?

After the first vaccination, anti-S1 immunoglobulin G (IgG) titers increased 47-fold in those who experienced SARS-CoV-2 and 2.6-fold in those who did not experience SARS-CoV-2.

However, after the second dose, anti-S1 IgG titers increased only 1.4-fold in participants who experienced SARS-CoV-2, compared 13-fold in individuals who did not experience SARS-CoV-2. Has increased to.

One week after the second dose, anti-S1 IgG titers were similar between the two groups.

“These data show a rapid and strong humoral response after vaccination in both cohorts, but a further increase in subjects who experienced SARS-CoV-2 after the second vaccination was minimal. “The team said.

Similarly, subjects who had not experienced SARS-CoV-2 had an increased antigen-specific ASC response after each vaccination, whereas participants who experienced SARS-CoV-2 compared to after the second vaccination. No circulating antigen-specific ASC was detected. First dose.

After the second dose, decreased circulating antigen-specific ASC of S1, S2, and RBD was observed among participants who experienced SARS-CoV-2.

What is the meaning of research?

“Here, a strong antibody response was observed in individuals who had not been treated with SARS-CoV-2,” Herati et al.

“In contrast, subjects who experienced SARS-CoV-2 responded strongly to the first dose of the vaccine due to increased antibody and antigen-specific ASC responses, but not so strongly after the second dose of the vaccine. It was, “they wrote.

Researchers say the findings underscore the need to further investigate the possible effects of previous immunological experience with SARS-CoV-2 on the response to the COVID-19 vaccine. ..

“Future studies may be needed to determine if a more optimal dosing regimen is needed for durable protective immunity against infection with the SARS-CoV-2 virus,” they said. I have concluded.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.