Comparison of IgG and Neutralizing Antibody Responses After One or Two Doses of COVID-19 MRNA Vaccine in Previously Infected and Uninfected Individuals

Background: Recent reports have suggested that among individuals previously infected with SARS-CoV-2, a single mRNA vaccine dose is sufficient to elicit high levels of immunity.

Methods: We compared anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-angiotensin-converting enzyme (ACE2) receptor binding following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history. Participants were analysed before and after mRNA vaccination (BNT162b2/Pfizer or mRNA-1273/Moderna) in a community-based, home-collected, longitudinal serosurvey in the Chicago area (USA); none reported hospitalization for COVID-19. Samples were collected in January and February 2021. Before vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+); the others who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results.

Findings: Of 307 unique vaccine recipients, 46 reported a prior COVID-19 diagnosis and were seropositive (COVID-19 +). Of the 261 with no history of acute viral diagnostic testing, 117 were seropositive and 144 seronegative before vaccination. The median age was 38 years (range 21-83) with 67 female and 33% male; 40% were non-White. Responses were evaluated after one ( = 142) or two ( = 191) doses of BNT162b2 or mRNA-1273 vaccine. After one dose, median post-vaccine IgG concentration and percent surrogate neutralization were each significantly higher among the COVID-19+ (median 48·2 µg/ml, IgG; > 99.9% neutralization) compared to the seropositives (3·6 µg /ml IgG; 56.5% neutralization) and seronegatives (2·6 µg /ml IgG; 38·3% neutralization). The latter two groups reached > 95% neutralization after the second vaccine dose.

Interpretation: After one dose of mRNA vaccine, individuals previously diagnosed with COVID-19 responded with high levels of anti-RBD IgG and surrogate neutralization of spike-ACE2 interaction. One dose of mRNA vaccine was not sufficient to generate comparably high responses among most persons previously infected with SARS-CoV-2 without a clinical COVID-19 diagnosis, nor among seronegative persons.

Funding: National Science Foundation 2035114, NIH 3UL1TR001422-06S4, and Northwestern University Office of Research.