SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared to SARS-CoV-2 mRNA vaccinations

 Elizabeth M. Anderson, Theresa Eiloa, Eileen Goodwin, Marcus J. Bolton, Sigrid Gouma, Rishi R. Goel, Mark M Painter, Sokratis A. Apostolidis, Divij Mathew, Debora Dunbar, Danielle Fiore, Amanda Brock, JoEllen Weaver, John S. Millar, Stephanie DerOhannessian, The UPenn COVID Processing Unit, Allison R. Greenplate, Ian Frank, Daniel J Rader, E John Wherry,  

View ORCID ProfileScott E. Hensley

doi: https://doi.org/10.1101/2021.09.30.21264363

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.09.30.21264363v1.full.pdf

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines elicit higher levels of antibodies compared to natural SARS-CoV-2 infections in most individuals; however, the specificities of antibodies elicited by vaccination versus infection remain incompletely understood. Here, we characterized the magnitude and specificity of SARS-CoV-2 spike-reactive antibodies from 10 acutely infected health care workers and 23 participants who received mRNA-based SARS-CoV-2 vaccines. We found that infection and primary mRNA vaccination elicited S1 and S2-reactive antibodies, while secondary vaccination boosted mostly S1 antibodies. Using magnetic bead-based absorption assays, we found that SARS-CoV-2 infections elicited a large proportion of original antigenic sin-like antibodies (from first exposure to infective) that bound efficiently to common seasonal human coronaviruses but poorly to SARS-CoV-2. In converse, vaccination only modestly boosted antibodies reactive to common seasonal human coronaviruses and these antibodies bound efficiently to SARS-CoV-2. Our data indicate that SARS-CoV-2 mRNA vaccinations elicit fundamentally different antibody responses compared to SARS-CoV-2 infections.

Competing Interest Statement

E.J.W. has consulting agreements with and/or is on the scientific advisory board for Merck, Elstar, Janssen, Related Sciences, Synthekine and Surface Oncology. E.J.W. is a founder of Surface Oncology and Arsenal Biosciences. E.J.W. is an inventor on a patent (U.S. patent number 10,370,446) submitted by Emory University that covers the use of PD-1 blockade to treat infections and cancer. S.E.H. has received consultancy fee from Sanofi Pasteur, Lumen, Novavax, and Merck for work unrelated to this report.

Clinical Trial

n/a, study was completed with de-identified samples from a separate study

Funding Statement

This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00015. This work was supported in part by institutional funds from the University of Pennsylvania and NIH U19AI082630 (S.E.H. and E.J.W.). E.M.A. was supported by the NIH Training in Virology T32 Program (T32-AI-007324). We thank J. Lurie, J. Embiid, J. Harris, and D. Blitzer for philanthropic support. We thank all members of the Penn COVID-19 Sample Processing Unit. We would like to thank David Anderson for assistance with the graphical abstract. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.

https://www.medrxiv.org/content/10.1101/2021.09.30.21264363v1

Effectiveness of mRNA-1273 against Delta, Mu, and other emerging variants

 Katia Bruxvoort, Lina S. Sy, Lei Qian, Bradley K. Ackerson, Yi Luo, Gina S. Lee, Yun Tian, Ana Florea, Michael Aragones, Julia E. Tubert, Harpreet S. Takhar, Jennifer H. Ku, Yamuna D. Paila, Carla A. Talarico, Hung Fu Tseng

doi: https://doi.org/10.1101/2021.09.29.21264199

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.09.29.21264199v1.full.pdf

Abstract

Background: Real-world studies have found high vaccine effectiveness (VE) of mRNA-based COVID-19 vaccines, but reduced VE against the Delta variant and waning protection have been reported, with few studies examining mRNA-1273 variant-specific VE. Methods: We conducted a test-negative case-control study at Kaiser Permanente Southern California. Whole genome sequencing was conducted for SARS-CoV-2 positive specimens collected from 3/1/2021 to 7/27/2021. Test-positive cases were matched 1:5 to test-negative controls on age, sex, race/ethnicity, and specimen collection date. Outcomes included SARS-CoV-2 infection and hospitalization. Exposures were 2 doses or 1 dose of mRNA-1273 ≥14 days prior to specimen collection versus no COVID-19 vaccination. Conditional logistic regression was used to compare odds of vaccination among cases versus controls, adjusting for confounders. VE was calculated as (1-odds ratio)x100%. Results: The study included 8,153 cases and their matched controls. Two-dose VE (95% confidence interval) was 86.7% (84.3-88.7%) against Delta infection, 98.4% (96.9-99.1%) against Alpha, 90.4% (73.9-96.5%) against Mu, 96-98% against other identified variants, and 79.9% (76.9-82.5%) against unidentified variants. VE against Delta declined from 94.1% (90.5-96.3%) 14-60 days after vaccination to 80.0% (70.2-86.6%) 151-180 days after vaccination. Waning was less pronounced for non-Delta variants. VE against Delta was lower among individuals aged ≥65 years (75.2% [59.6-84.8%]) than those aged 18-64 years (87.9% [85.5-89.9%]). VE against Delta hospitalization was 97.6% (92.8-99.2%). One-dose VE was 77.0% (60.7-86.5%) against Delta infection. Conclusions: Two doses of mRNA-1273 were highly effective against all SARS-CoV-2 variants. However, VE against Delta moderately declined with increasing time since vaccination.

Competing Interest Statement

KJB, LSS, LQ, BKA, YL, GSL, YT, AF, MA, JET, HST, JHK, and HFT are employees of Kaiser Permanente Southern California, which has been contracted by Moderna for the conduct of this present study. CAT and YDP are employees of and shareholders in Moderna Inc. KJB received funding from GlaxoSmithKline, Dynavax, Pfizer, Gilead, and Seqirus unrelated to this manuscript. LSS received funding from GlaxoSmithKline, Dynavax, and Seqirus unrelated to this manuscript. LQ received funding from GlaxoSmithKline and Dynavax unrelated to this manuscript. BKA received funding from GlaxoSmithKline, Dynavax, Seqirus and Pfizer unrelated to this manuscript. YL received funding from GlaxoSmithKline, Dynavax, Seqirus and Pfizer unrelated to this manuscript. GSL received funding from GlaxoSmithKline unrelated to this manuscript. YT received funding from GlaxoSmithKline unrelated to this manuscript. AF received funding from Pfizer, GlaxoSmithKline, CDC, and Gilead unrelated to this manuscript. MA received funding from Pfizer unrelated to this manuscript. JET received funding from Pfizer unrelated to this manuscript. HST received funding from GlaxoSmithKline, Pfizer, ALK, and Wellcome unrelated to this manuscript. JHK received funding from GlaxoSmithKline unrelated to this manuscript. HFT received funding from GlaxoSmithKline and Seqirus unrelated to this manuscript; HFT also served in advisory boards for Janssen and Pfizer.

Clinical Trial

N/A

Funding Statement

This study was funded by Moderna Inc. Medical writing and editorial assistance was provided by Srividya Ramachandran, PhD, and Jared Mackenzie, PhD, of MEDiSTRAVA in accordance with Good Publication Practice (GPP3) guidelines, funded by Moderna Inc, and under the direction of the authors.

https://www.medrxiv.org/content/10.1101/2021.09.29.21264199v1

Immune Memory Response After Booster of mRNA-1273 for SARS-CoV-2

 Laurence Chu, David Montefiori, Wenmei Huang, Biliana Nestorova, Ying Chang, Andrea Carfi, Darin K Edwards, Judy Oestreicher, Holly Legault, Bethany Girard, Rolando Pajon, Jacqueline M Miller, Rituparna Das, Brett Leav, Roderick McPhee

doi: https://doi.org/10.1101/2021.09.29.21264089

This article is a preprint and has not been certified by peer review [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.

PDF: https://www.medrxiv.org/content/10.1101/2021.09.29.21264089v1.full.pdf

Abstract

Rising breakthrough infections of coronavirus-2 (SARS-CoV-2) in previously immunized individuals has raised concerns for a potential booster to combat suspected waning immunity and new variants. In this study, participants immunized 6-8 months earlier with a primary series of two doses of 50 or 100 μg of mRNA-1273 were administered a booster injection of 50 μg of mRNA-1273. Neutralizing antibody levels at one month after the booster were 1.7-fold higher than those one-month post primary series second injection meeting the prespecified criteria for noninferiority, and indicating an immune memory response. The reactogenicity after the booster dose was similar to that after the second dose in the primary series of two doses of mRNA-1273 (50 or 100 μg) with no serious adverse events reported in the one-month follow-up period. These results demonstrate that a booster injection of mRNA-1273 in previously immunized individuals stimulated an immune response greater than the primary vaccination series.

Competing Interest Statement

Wenmei Huang, Ying Chang, Judy Oestreicher, Holly Legault, Biliana Nestorova, Bethany Girard, Rolando Pajon, Jacqueline M.Miller, Andrea Carfi, Darin K. Edwards, Rituparna Das, Brett Leav, and Roderick McPhee are employees of Moderna, Inc., and may hold stock/stock options in the company.

Clinical Trial

NCT04405076

Funding Statement

Parts A and B of the phase 2 trial (mRNA-1273 P201 trial/open-label extension; NCT04405076) were supported in part with Federal funds from the Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority, under Contract No. 75A50120C00034, and Moderna, Inc.

https://www.medrxiv.org/content/10.1101/2021.09.29.21264089v1