A team of researchers led by Thomas W. McDade of Northwestern University suggests people who were previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), may require only one dose of the mRNA vaccine to obtain immunity.
Their results showed high immunoglobulin G (IgG) antibody levels and neutralization activity before vaccination, which surpassed a 95% neutralizing activity after the first dose.
The researchers write:
We document strong antibody responses to the first vaccine dose among individuals with confirmed cases of COVID-19, consistent with recent reports. We document a pattern of mild and heterogeneous responses to the first dose among individuals previously unexposed to SARS-CoV-2, with more robust responses following the second dose, consistent with clinical trials data.”
The study “Comparison of IgG and neutralizing antibody responses after one or two doses of COVID-19 mRNA vaccine in previously infected and uninfected persons” is available as a preprint on the medRxiv* server, while the article undergoes peer review.
The researchers recruited 8,000 people who had not been vaccinated yet to participate in the study from April to December 2020. Participants were required to complete a questionnaire regarding the information on their COVID-19 status and any history of symptoms. They also donated blood samples through a finger-prick-dried blood spot collection through the mail or on-site pick up.
Participants were categorized into three groups: people who reported prior infection before vaccination, people with no prior infection but seronegative, and people with no prior infection but seropositive. For the participants that never took a COVID-19 test, the researchers classified them as either seropositive or seronegative, depending on the existence of IgG antibodies in the blood samples.
The team then contacted participants on their vaccination status through February 2021, and if so, if they had received one or two doses of either Pfizer-BioNTech or Moderna’s vaccine.
The researchers excluded blood samples that were collected 9 days before receiving the first dose or 5 days after receiving the second dose.
Symptoms and neutralization antibody findings
People with prior infection reported a median of 5 coronavirus symptoms and a median of 138 days between receiving their positive diagnosis and vaccination.
Among the seropositive group who never tested for COVID-19 infection, they reported a median of one symptom. This group also had lower IgG antibody levels and neutralizing activity than participants who recovered from a prior infection.
Immunity after one vaccine dose
The researchers observed a boost in IgG antibody levels specific to the receptor-binding domain of the spike protein and an increase in neutralizing activity in participants who had a history of infection after receiving the first mRNA. Specifically, the median IgG levels increased by a factor of 34.8, and all blood samples showed 95% or more neutralizing activity.
While not as high as people with prior infection, the seropositive group also showed a surge in immune function after receiving their first dose. Their IgG levels increased by a factor of 5.3, and their median neutralizing activity was 62.8%. Only 5 of the 33 seropositive samples showed 95% or more neutralization. The boost in immunity in the seropositive group was slightly more significant than the seronegative group that received the dose.
Second vaccine dose shows minimal benefit to people with prior infection
When given the second mRNA dose, people who were previously infected with COVID-19 continued to show similar IgG levels and neutralization as when they received their first dose.
In contrast, the seropositive group showed an 8.1 times increase in IgG levels and 1.6 times higher neutralization compared to when they received their first dose. However, the researchers note that the seropositive group still had lower immune activity than the prior infection group. About 30% of participants in the seropositive group did not achieve 95% neutralization after the second dose. Although, it’s possible the sampling timeframe was too short to observe this change in immunity.
Both the seropositive and seronegative groups had similar IgG antibody concentration and neutralization after the second dose.
Based on the lowered immunity observed in the seropositive group compared to the prior infection, the researchers suggest future studies on vaccine effectiveness should take into account the greater immune response in patients with severe prior infection. They may cause overestimations of the level of priming immunity that isn’t generalizable to seropositive individuals who may have had only mild exposure to the virus.
Responses in the seropositive group suggest that immunity following the first vaccine dose is significantly lower than the convalescent COVID-19 group. And like the seronegative group, two doses are required for the seropositive group to attain a level of protection that is comparable to the COVID-19 group.”
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.