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Comparison of IgG and Neutralizing Antibody Responses After One or Two Doses of COVID-19 mRNA Vaccine in Previously Infected and Uninfected Persons (WP-21-13)

Alexis Demonbreun, Amelia Sancilio, Matt Velez, Daniel Ryan, Rana Saber, Lauren Vaught, Nina Reiser, Ryan Hsieh, Richard D’Aquila, Brian Mustanski, Elizabeth McNally, and Thomas McDade

Objective: To compare anti-SARS-CoV-2 spike receptor binding domain (RBD) IgG antibody concentrations and antibody-mediated neutralization of spike-ACE2 receptor binding in vitro following vaccination of non-hospitalized participants by sero-status and acute virus diagnosis history.

Methods: Participants were studied before and after mRNA vaccination in a community-based, home-collected, longitudinal serosurvey; none reported hospitalization for COVID-19. Prior to vaccination, some reported prior positive acute viral diagnostic testing and were seropositive (COVID-19+). Participants who did not report acute viral diagnostic testing were categorized as seropositive or seronegative based on anti-spike RBD IgG test results. Primary measures were anti-spike RBD IgG concentration and percent antibody-mediated neutralization of spike protein-ACE2 interaction prior to vaccination, and after one or two doses of vaccine.

Results: Of 290 unique vaccine recipients, 42 reported a prior COVID-19 diagnosis and were seropositive (COVID-19+). Of the 248 with no history of acute viral diagnostic testing, 105 were seropositive and 143 seronegative before vaccination. The median age was 38yrs (range 21-83) with 65% female and 35% male; 40% were non-white. Responses were evaluated after one (n=140) or two (n=170) doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. After one dose, median post-vaccine IgG concentration and percent neutralization were each significantly higher among the COVID-19+ group (median 47.7 μg/ml, IgG; >99.9% neutralization) compared to the seropositives (3.4 μg /ml IgG; 62.8% neutralization) and seronegatives (2.2 μg /ml IgG; 39.5% neutralization). The latter two groups reached >95% neutralization after the second vaccine dose.

Conclusions: A prior outpatient COVID-19 diagnosis was associated with strong anti-spike RBD IgG and in vitro neutralizing responses after one vaccine dose. Persons seropositive for anti-spike RBD IgG in the absence of acute viral diagnostic testing, and those who were seronegative, required two doses to achieve equivalently high levels of IgG and neutralization activity. One mRNA vaccine dose is not sufficient to generate in vitro evidence of strong protection against COVID-19 among most persons previously infected with SARS-CoV-2, nor among seronegative persons.

This paper has now been published in EClinicalMedicine. 

Alexis Demonbreun, Assistant Professor of Pharmacology, Northwestern University

Amelia Sancilio, Postdoctoral Fellow, Institute for Policy Research, Northwestern University

Matt Velez, Center for Genetic Medicine, Northwestern University

Daniel Ryan, Institute for Sexual and Gender Minority Health and Wellbeing, Northwestern University

Rana Saber, Institute for Sexual and Gender Minority Health and Wellbeing, Northwestern University

Lauren Vaught, Center for Genetic Medicine, Northwestern University

Nina Reiser, Center for Genetic Medicine, Northwestern University

Ryan Hsieh, Center for Genetic Medicine, Northwestern University

Richard D’Aquila, Howard Taylor Ricketts, MD, Professor of Medicine, Northwestern University

Brian Mustanski, Professor of Medical Social Sciences and IPR Associate, Northwestern University

Elizabeth McNally, Elizabeth J. Ward Professor of Genetic Medicine, Northwestern University

Thomas McDade, Carlos Montezuma Professor of Anthropology and IPR Fellow, Northwestern University

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