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Researchers at the NYU Grossman School of Medicine have shown that a second dose of the Pfizer-BioNTech BNT162b2 vaccine may not offer any additional protection against coronavirus disease 2019 (COVID-19) over one dose among individuals previously infected with the causative agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a study evaluating immune responses to the Pfizer-BioNTech vaccine, Ramin Herati and colleagues observed robust humoral (antibody) responses following two vaccine doses among individuals without previous SARS-CoV-2 infection (SARS-CoV-2-naïve). However, SARS-CoV-2-experienced participants had a robust humoral response to the first dose but a muted response to the second dose. In fact, SARS-CoV-2-experienced individuals had lower circulating levels of antigen-specific antibody-secreting cells (ASCs) following the second dose than they did following the first dose. A pre-print version of the research paper is available on the medRxiv* server while the article undergoes peer review.
SARS-CoV-2 infection triggers important antibody responses
The SARS-COV-2 infection process is mediated by a surface structure called the spike protein, which binds to the host cell receptor angiotensin-converting enzyme 2 (ACE2) via its receptor-binding domain (RBD). The spike protein comprises two subunits. Subunit 1 (S1) contains the RBD, which attaches to ACE2 via a receptor-binding motif (RBM) and subunit 2 (S2) enables the viral membrane to fuse with the host cell. Following natural infection, antibodies targeting the spike RBD are thought to account for more than 90% of the neutralizing activity against SARS-CoV-2. Research has shown that pre-existing immunity to SARS-CoV-2 is associated with protection against reinfection in humans and animals.
Recently approved vaccines are based on the spike protein
Both the Pfizer-BioNTech and Moderna vaccines that have recently been FDA-approved for emergency use against SARS-CoV-2 are mRNA-based vaccines that encode a region of the spike protein. These novel mRNA vaccines have been considered critical to ending the COVID-19 pandemic since they were shown to induce robust humoral responses against SARS-CoV-2 and to be 94% effective at preventing disease in large-scale clinical trials. However, efficacy trials excluded individuals with a prior diagnosis of COVID-19 and only focused on individuals without previous SARS-CoV-2 exposure.
What did the researchers do?
The team evaluated immune responses among 32 individuals (aged 24 to 62 years) who received the Pfizer-BioNTech BNT162b2 vaccine as a two-dose regimen. Thirteen of the participants (median age 41 years) had previously been infected with SARS-CoV-2 and the remaining 19 (median age 39 years) were SARS-CoV-2-naïve. All participants had immune responses assessed at approximate intervals before and after each dose of the vaccine.
What did the study find?
Following the first vaccine dose, anti-S1 immunoglobulin G (IgG) titers increased 47-fold among the SARS-CoV-2-experienced individuals and 2.6-fold among the SARS-CoV-2-naïve participants. However, following the second dose, anti-S1 IgG titers only increased 1.4-fold among the SARS-CoV-2-experienced participants, whereas they increased 13-fold among SARS-CoV-2-naïve individuals. One week after the second dose, anti-S1 IgG titers were similar between the two groups. Similarly, while antigen-specific ASC responses increased following each vaccine dose among the SARS-CoV-2-naïve subjects, fewer circulating antigen-specific ASCs were detected among SARS-CoV-2-experienced participants after the second vaccine, compared with after the first dose. After the second dose, reductions in circulating antigen-specific ASCs were observed for S1, S2 and the RBD among SARS-CoV-2-experienced participants.
What are the implications of the study?
The researchers say the findings highlight the need to investigate further the impact that prior immunological experience of SARS-CoV-2 may have on responses to COVID-19 vaccines.
Preprint available (Feb. 9, 2021):
