Study finds one mRNA vaccine dose after SARS-CoV-2 infection produces highest neutralizing antibody titers

As mass vaccination programs across the US and the UK stall, researchers from the University of Arizona have investigated the neutralizing antibody response that different mRNA vaccines induce in both previously convalescent and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) naïve individuals.

Study: Neutralizing Antibody Response to Pseudotype SARS-CoV-2 Differs between mRNA-1273 and BNT162b2 COVID-19 Vaccines and by History of SARS-CoV-2 Infection. Image Credit: ktsdesign/ Shutterstock

A preprint version of the group’s study is available on the medRxiv* server while the article undergoes peer review.

The study

Traditionally, vaccines are created from an inactivated/attenuated form of the virus. Exposing the immune system to this allows plasma cells and memory B cells to be created specifically to viral surface proteins with relatively little risk of harm. However, if inactivated viruses reactivate or attenuated viruses receive new traits through horizontal gene transfer, they can once again become dangerous.

mRNA vaccines avoid this possibility – rather than providing a protein, mRNA vaccines contain a string of genetic material encoding for a viral surface protein (normally the receptor-binding domain of the spike protein) and rely on the host’s cellular machinery to transcribe it. This allows immunity to be gained with fairly little risk.

The researchers had prospective participants fill out a survey to collect sociodemographic information and health characteristics and then asked them to collect a weekly nasal swab. Further swabs and saliva specimens were collected at the onset of at least one symptom of coronavirus disease 2019 (COVID-19).

Further surveys were also required to describe the symptoms at the start and end of illness. Serum specimens were collected at the beginning of the study and every three months, with convalescent serum collected 30 days following a positive SARS-CoV-2 test result. Those who received mRNA vaccines provided serum samples 14 and 21 days following each dose. Nearly 4000 participants were enrolled in total. Vaccination status was determined through self-reporting, images of vaccine cards, and review of records and state immunization systems.

Swabs were tested for SARS-CoV-2 by RT-PCR assays, and serum-neutralizing antibodies were measured against spike protein pseudotype viruses. The researchers looked at the log10 titers of neutralizing antibodies and transformed them back to estimated mean titers to analyze the results. Neutralizing antibodies following infection were analyzed using one-sample t-tests, and neutralizing antibodies following vaccination were modeled on a linear mixed-effects model. Associations between the factors examined by the surveys and the neutralizing antibodies were tested using Pearsons’ chi-squared, Fisher’s exact tests, or one-way ANOVAs.

In total, 170 participants showed evidence of SARS-CoV-2 infection before vaccination, 139 showed no history of infection before vaccination or afterward, and 50 of those submitted both post-vaccination and post-infection sera. The vast majority of the subjects were white, roughly half were female, and 39-58% were nurses or other health care providers. 92% of confirmed infections were asymptomatic, and most infections were associated with fever and positive testing. 158 of the 170 participants with evidence of infection had neutralizing antibodies present in their sera. Infection characteristics, such as the presence of symptoms, did not affect neutralizing antibody titer. There was also no association between neutralizing antibody titer and viral RNA load.

108 of 139 vaccinated individuals showed evidence of neutralizing antibodies following their first dose, with younger individuals showing higher antibody production. Following the second dose, 138/139 individuals were producing detectable titers of neutralizing antibodies. Interestingly, underweight, overweight, and obese individuals showed higher neutralizing antibody titers than those with a normal BMI following the second dose.

Those who received the mRNA-1273 (Moderna) vaccine showed higher neutralizing antibody results following the first and second dose compared to those who received the BNT162b2 (Pfizer-BioNTech) vaccine. As several studies have previously reported, the researchers confirm that those vaccinated following infection with SARS-CoV-2 showed significantly higher antibody titers. These were once again higher in those who had received the Moderna vaccine but not by a significant margin.


The authors highlight the importance of their results in identifying the sociodemographic factors that can play a role in immunity and the pre-infection health of the individual. The differing responses to each vaccine are also very useful in helping to inform vaccine manufacturers, as well as helping public health policymakers reach informed decisions – for example, providing the Moderna vaccine to individuals who will be more at risk if they catch the disease. The study also confirms the results of previous investigations – that the greatest protection is afforded to those who have not only been vaccinated but those who have been infected, recovered and then vaccinated. In these individuals, the second dose did not boost antibody titer at all.

*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

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