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Master of Public Health

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

AUTHORS

Tyner HL , Burgess JL , Grant L , Gaglani M , Kuntz JL , Naleway AL , Thornburg NJ , Caban-Martinez AJ , Yoon SK , Herring MK , Beitel SC , Blanton L , Nikolich-Zugich J , Thiese MS , Pleasants JF , Fowlkes AL , Lutrick K , Dunnigan K , Yoo YM , Rose S , Groom H , Meece J , Wesley MG , Schaefer-Solle N , Louzado-Feliciano P , Edwards LJ , Olsho LEW , Thompson MG , . Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 12 20; ().

ABSTRACT

BACKGROUND: Data on the development of neutralizing antibodies against SARS-CoV-2 after SARS-CoV-2 infection and after vaccination with messenger RNA (mRNA) COVID-19 vaccines are limited.

METHODS: From a prospective cohort of 3,975 adult essential and frontline workers tested weekly from August 2020 to March 2021 for SARS-CoV-2 infection by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay irrespective of symptoms, 497 participants had sera drawn after infection (170), vaccination (327), and after both infection and vaccination (50 from the infection population). Serum was collected after infection and each vaccine dose. Serum-neutralizing antibody titers against USA-WA1/2020-spike pseudotype virus were determined by the 50% inhibitory dilution. Geometric mean titers (GMTs) and corresponding fold increases were calculated using t-tests and linear mixed effects models.

RESULTS: Among 170 unvaccinated participants with SARS-CoV-2 infection, 158 (93%) developed neutralizing antibodies (nAb) with a GMT of 1,003 (95% CI=766-1,315). Among 139 previously uninfected participants, 138 (99%) developed nAb after mRNA vaccine dose-2 with a GMT of 3,257 (95% CI = 2,596-4,052). GMT was higher among those receiving mRNA-1273 vaccine (GMT =4,698, 95%CI= 3,186-6,926) compared to BNT162b2 vaccine (GMT=2,309, 95%CI=1,825-2,919). Among 32 participants with prior SARS-CoV-2 infection, GMT was 21,655 (95%CI=14,766-31,756) after mRNA vaccine dose-1, without further increase after dose-2.

CONCLUSIONS: A single dose of mRNA vaccine after SARS-CoV-2 infection resulted in the highest observed nAb response. Two doses of mRNA vaccine in previously uninfected participants resulted in higher nAb to SARS-CoV-2 than after one dose of vaccine or SARS-CoV-2 infection alone. Neutralizing antibody response also differed by mRNA vaccine product.

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