Study supports single-dose COVID-19 vaccine strategy for previously infected individuals

Researchers in the Netherlands have provided evidence that a single dose of Pfizer-BioNTech’s coronavirus disease 2019 (COVID-19) vaccine is sufficient to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among people who have already been infected with the virus.

The urgent need for, but limited availability of, SARS-CoV-2 vaccines worldwide has led to widespread consideration of dose sparing strategies, particularly single vaccine dosing of individuals with prior SARS-CoV-2 infection,” says the team from the University of Amsterdam, the Public Health Service of Amsterdam and members of the RECoVERED Study Group.

Menno de Jong and colleagues showed that among previously infected individuals, one dose of Pfizer-BioNTech’s BNT162b2 vaccine-induced neutralizing antibody titers exceeded those observed among infection-naïve individuals who had received two doses.

These findings support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection,” writes the team.

A pre-print version of the research paper is available on the medRxiv* server, while the article undergoes peer review.

“Making use of immunological memory”

Since the COVID-19 outbreak first began in late December 2019, intense global efforts to rapidly develop and clinically test candidate vaccines against SARS-CoV-2 have led to the emergency use authorization of several vaccines that are now being rolled out in many countries.

However, although mass vaccination represents the most promising approach to combating the pandemic, many regions are hampered by limited supplies and resources.

Making use of immunological memory after prior natural SARS-CoV-2 infection, single dosing represents one such strategy for vaccines requiring two doses for optimal efficacy,” says de Jong and colleagues.

Indeed, some studies involving healthcare workers have shown similar or higher antibody responses to a single vaccine after prior infection, compared with two doses following no prior infection.  

However, these studies were small, restricted to relatively young and healthy individuals with mostly mild disease and provided limited information on the possible influence of COVID-19 severity and the duration since infection.

What did the researchers do?

The researchers examined the titers and breadth of antibody responses to a single dose of Pfizer-BioNTech’s BNT162b2 vaccine in 155 individuals previously infected with SARS-Cov-2 who varied widely by age, the presence of comorbidities, COVID-19 severity and time since infection (which ranged from one to 15 months).  

Serum antibody titers were determined at the time of vaccination and one week after vaccination. The antibody responses were compared with those observed among 49 SARS-CoV-2-naive healthcare workers (median age 44 years; range 33 to 53 years) who had received two vaccine doses.

The median age of the previously-infected participants was 55 years (range 33 to 61 years), and 44% had one or more comorbidities. Infections were classified as mild in 33% of cases, moderate in 45%, and severe or critical in 22%.

What did they find?

Anti-SARS-CoV-2 immunoglobulin G (IgG) antibody titers were wide-ranging before vaccination, with higher levels observed in participants with previous severe or critical COVID-19.

One week after vaccination, IgG titers against the viral spike protein and its receptor-binding domain (RBD) increased by a median of 29.4-fold  and 27.6-fold, respectively.

The spike protein is the main structure SARS-CoV-2 uses to infect host cells, and its RBD is the primary target of antibodies following natural infection or vaccination.

Levels of neutralizing antibodies also increased 12-fold one week following vaccination, compared with prior to vaccination, and exceeded those observed among the fully vaccinated infection-naïve controls.

A Bayesian multilevel regression model showed that pre-vaccination neutralizing antibody titers had the largest positive mean effect size on post-vaccination titers.  

Pre-vaccination neutralization titers were associated with higher neutralization titers following vaccination, independent of COVID-19 severity, the presence of comorbidities and the time interval between infection and vaccination.

The findings support wide implementation of a single-dose strategy after prior infection

The researchers say the study demonstrates that higher levels of neutralizing antibodies are achieved within one week of a single dose of BNT162b2 in previously infected individuals, compared with those observed in fully vaccinated SARS-CoV-2-naive individuals, irrespective of the time since infection.

The findings of this study support wide implementation of a single-dose mRNA vaccine strategy after prior SARS-CoV-2 infection to save vaccines and resources, hence expediting vaccination uptake at community levels worldwide,” concludes de Jong and colleagues.

*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.

Journal reference:
Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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