Researchers in Spain have conducted the most extensive study to date investigating the effectiveness of vaccinating healthcare workers with a single dose of the Pfizer-BioNTech vaccine to protect against coronavirus disease 2019 (COVID-19).

The team says one dose of the vaccine induced a much stronger antibody response against the causative agent – severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – among healthcare workers who had previously been infected with the virus than among those who had not.

The researchers say that given the controversy over how to ensure adequate immunization of the population in times of vaccine shortages, the study findings might help inform decisions over whether to only administer a single dose in some cases.

“So far, this is the largest study investigating the immune response after one dose of Pfizer-BioNTech BNT162b2 vaccine,” writes Maria Velasco from the Alcorcon Foundation University Hospital in Madrid and colleagues. “These data may inform prioritization of the booster dose in times of vaccine shortage.”

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

The current challenges faced in controlling COVID-19

Currently, the primary approach to controlling the COVID-19 pandemic is the rollout of recently-approved vaccines and continued adherence to social distancing and hygiene practices.

However, limited vaccine supplies present challenges in terms of ensuring a sufficient proportion of the population is vaccinated for herd immunity to be reached.

The standard vaccination protocol for the Pfizer-BioNTech vaccine is a 2-dose regimen separated by an interval of 3 to 4 weeks.

However, a single-dose regimen for some individuals who do not necessarily require a booster shot could help to ensure herd immunity is achieved in the setting of vaccine shortages.

Velasco and colleagues say that data on immune responses to a single dose of the Pfizer-BioNTech vaccine is currently limited to a few observational studies with a small number of patients.

“Moreover, the impact of previous natural infection on vaccine response is not well known,” they add.

What did the researchers do?

The team investigated the antibody response induced by a single dose of the Pfizer-BioNtech BNT162b2 vaccine among 641 healthcare workers (aged a mean of 45.8 years) who had previously participated in a SARS-CoV-2 seroprevalence survey conducted in April and November of 2020.

Participants were divided into three groups, according to whether they were seronegative for the virus in both surveys (SARS-CoV-2 naïve); transient seropositive (positive in the first survey, but not the second) or persistent seropositive (positive in both surveys).

Seropositive individuals were further divided by COVID-19 severity into those with asymptomatic infection, those with mild-to-moderate disease treated on an out-patient basis, and those with severe disease requiring hospitalization.

Blood samples were taken from the participants after they had received one dose of the vaccine and just before they received a second dose (21 days after the first dose).

The samples were tested for immunoglobulin (IgG) antibodies against a SARS-CoV-2 surface protein called a spike. The spike protein is the main structure the virus uses to bind host cells and a major target of the neutralizing antibodies induced by infection or vaccination.

What did the study find?

The median anti-spike IgG titer induced by a single vaccine dose was approximately 20 times higher among previously seropositive participants (22,267.3 arbitrary units [AU]/mL) than among SARS-CoV-2 naïve participants (median 1,022.3 AU/mL).

Compared with SARS-CoV-2 naïve participants, median anti-spike IgG titers were about 4 times higher among transient seropositive individuals (3,860.0 AU/mL) and about 34 times higher among persistent positive individuals (34,551.6 AU/mL).

Among those who were seropositive, the level of disease severity was also associated with anti-spike IgG titers. The median titer for asymptomatic infection was 15,386.4 AU/mL, compared with 24,388.8 AU/mL for mild-to-moderate disease and 43,671.7 AU/mL for severe disease.

“Our serological evaluation of healthcare workers showed a dramatic differential response 3 weeks after a single dose of the BNT162b2 vaccine, according to previous exposure to SARS-CoV2 and serological status,” writes Velasco and colleagues.

The combination of previous clinical COVID-19 and the presence of anti-spike IgG antibodies prior to vaccination were strong predictors of a robust serologic response to a single vaccine dose, says the team.

What do the authors suggest?

“Our results suggest that deferring the second dose of the vaccine for some individuals with a predictable strong serologic response may not be a high-risk strategy,” say the researchers.

This would enable the vaccination of other at-risk individuals until vaccine availability is sufficient for the standard, clinically tested protocol (two-doses 3 to 4 weeks apart) to be followed, they conclude.

*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.

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.