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[Preprint]. 2021 May 16:2021.05.13.444010.
doi: 10.1101/2021.05.13.444010.

Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants

Amarendra Pegu #  1 , Sarah O'Connell #  1 , Stephen D Schmidt #  1 , Sijy O'Dell #  1 , Chloe A Talana  1 , Lilin Lai  2 , Jim Albert  3 , Evan Anderson  2 , Hamilton Bennett  4 , Kizzmekia S Corbett  1 , Britta Flach  1 , Lisa Jackson  5 , Brett Leav  4 , Julie E Ledgerwood  1 , Catherine J Luke  6 , Mat Makowski  3 , Paul C Roberts  6 , Mario Roederer  1 , Paulina A Rebolledo  7 , Christina A Rostad  2 , Nadine G Rouphael  7 , Wei Shi  1 , Lingshu Wang  1 , Alicia T Widge  1 , Eun Sung Yang  1 ; mRNA-1273 Study Group; John H Beigel  6 , Barney S Graham  1 , John R Mascola  1 , Mehul S Suthar  2 , Adrian McDermott  1 , Nicole A Doria-Rose  1
Affiliations

Durability of mRNA-1273-induced antibodies against SARS-CoV-2 variants

Amarendra Pegu et al. bioRxiv. .

Update in

  • Durability of mRNA-1273 vaccine-induced antibodies against SARS-CoV-2 variants.
    Pegu A, O'Connell SE, Schmidt SD, O'Dell S, Talana CA, Lai L, Albert J, Anderson E, Bennett H, Corbett KS, Flach B, Jackson L, Leav B, Ledgerwood JE, Luke CJ, Makowski M, Nason MC, Roberts PC, Roederer M, Rebolledo PA, Rostad CA, Rouphael NG, Shi W, Wang L, Widge AT, Yang ES; mRNA-1273 Study Group§; Beigel JH, Graham BS, Mascola JR, Suthar MS, McDermott AB, Doria-Rose NA, Arega J, Beigel JH, Buchanan W, Elsafy M, Hoang B, Lampley R, Kolhekar A, Koo H, Luke C, Makhene M, Nayak S, Pikaart-Tautges R, Roberts PC, Russell J, Sindall E, Albert J, Kunwar P, Makowski M, Anderson EJ, Bechnak A, Bower M, Camacho-Gonzalez AF, Collins M, Drobeniuc A, Edara VV, Edupuganti S, Floyd K, Gibson T, Ackerley CMG, Johnson B, Kamidani S, Kao C, Kelley C, Lai L, Macenczak H, McCullough MP, Peters E, Phadke VK, Rebolledo PA, Rostad CA, Rouphael N, Scherer E, Sherman A, Stephens K, Suthar MS, Teherani M, Traenkner J, Winston J, Yildirim I, Barr L, Benoit J, Carste B, Choe J, Dunstan M, Erolin R, Ffitch J, Fields C, Jackson LA, Kiniry E, Lasicka S, Lee S, Nguyen M, Pimienta S, Suyehira J, Witte M, Bennett H, Altaras NE, Carfi A, Hurley M, Leav B, Pajon R, Sun W, Zaks T, Coler RN, Larsen SE, Neuzil KM, Lin… See abstract for full author list ➔ Pegu A, et al. Science. 2021 Sep 17;373(6561):1372-1377. doi: 10.1126/science.abj4176. Epub 2021 Aug 13. Science. 2021. PMID: 34385356 Free PMC article.

Abstract

SARS-CoV-2 mutations may diminish vaccine-induced protective immune responses, and the durability of such responses has not been previously reported. Here, we present a comprehensive assessment of the impact of variants B.1.1.7, B.1.351, P.1, B.1.429, and B.1.526 on binding, neutralizing, and ACE2-blocking antibodies elicited by the vaccine mRNA-1273 over seven months. Cross-reactive neutralizing responses were rare after a single dose of mRNA-1273. At the peak of response to the second dose, all subjects had robust responses to all variants. Binding and functional antibodies against variants persisted in most subjects, albeit at low levels, for 6 months after the primary series of mRNA-1273. Across all assays, B.1.351 had the greatest impact on antibody recognition, and B.1.1.7 the least. These data complement ongoing studies of clinical protection to inform the potential need for additional boost vaccinations.

One-sentence summary: Most mRNA-1273 vaccinated individuals maintained binding and functional antibodies against SARS-CoV-2 variants for 6 months.

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Conflict of interest statement

Competing interests:

Ms. Bennett and Dr. Leav are employees of Moderna, Inc.

Dr. Graham reports having a patent, International Patent Application No. WO/2018/081318 entitled “Prefusion Coronavirus Spike Proteins and Their Use” pending, and a patent, US Patent Application No. 62/972,886 entitled “2019-nCoV Vaccine” pending.

Dr. Anderson reports grants and personal fees from Pfizer, grants from Merck, grants from PaxVax, grants from Micron, grants and personal fees from Sanofi-Pasteur, grants from Janssen, grants from MedImmune, grants from GSK, personal fees from Medscape, personal fees from Kentucky Bioprocessing, Inc, outside the submitted work.

Dr. Rouphael reports grants from Pfizer, grants from Merck, grants from Sanofi-Pasteur, grants from Eli Lilly, grants from Quidel, outside the submitted work.

Figures

Figure 1.
Figure 1.. Neutralization of D614G and variant pseudoviruses is sustained for 6 months.
100 ug mRNA-1273 was delivered at Days 1 and 29. Each line represents the pseudovirus neutralization ID50s at Days 29 (4 weeks after first dose), 43 (two weeks after second dose), 119, and 209 for a single subject., n=8 per group. Neutralization activity of sera from subjects aged 18–55 (top row), 56–70 (middle row), and 71 + (bottom row) was measured against pseudoviruses bearing spike of D614G (left), B.1.1.7 (middle), or B.1.351 (right).
Figure 2.
Figure 2.. Binding and functional antibodies persist for 6 months following the second dose of mRNA-1273.
For all assays, sera from n=24 individuals were sampled at 4 timepoints. Subjects were vaccinated with 100 ug mRNA-1273 at Days 1 and 29. A, Pseudovirus neutralization, expressed as 50% inhibitory dilution (ID50). Dotted line, limit of detection (>20). B. Live-virus FRNT neutralization, expressed as 50% inhibitory dilution (ID50). Dotted line, limit of detection (>20). C. Binding to cell-surface expressed full length spike, measured by flow cytometry and expressed as median fluorescence intensity (MFI). D. Serum blocking of ACE2 binding to RBD, measured by MSD-ECLIA and expressed as fold reduction of ACE2 binding. Dotted line, limit of detection (>2). E. Binding to soluble spike protein S-2P, measured by MSD-ECLIA and expressed as area under the curve (AUC). F. Bindng to receptor-binding domain protein (RBD), measured by MSD-ECLIA and expressed as area under the curve (AUC).
Figure 3.
Figure 3.. The majority of Day 209 sera maintain activity against WA1, D614G, and variants.
Values are the percentage of sera (n=24 at each timepoint) for which antibodies were detected, for each variant. For pseudovirus and live-virus neutralization, samples were called detectable at ID50>20; for ACE2 blocking, at 2-fold decrease in signal; for S-2P and RBD binding, AUC>100; for cell-surface spike binding, MFI>100. nt, not tested.
Figure 4.
Figure 4.. Impact of variants on antibody functions is stable over time.
Sera from n=24 individuals were sampled at each timepoint. Fold change: geometric mean of ratios for each sample. A. ID50 in pseudovirus neutralization assays using D614G compared to B.1.1.7, B.1.351, P1, B.1.526, and B.1.429. B. ID50 in live virus FRNT neutralization assays using 83E (D614G) compared to B.1.1.7 or B.1.351. C. Blocking of ACE2 binding to WA1 RBD compared to B.1.1.7 RBD or B.1.351 RBD.
Figure 5.
Figure 5.. Impact of variants on antibody binding is stable over time.
Sera from n=24 individuals were sampled at each timepoint. Fold change: median of ratios for each sample. A. Binding of cell-surface expressed full-length spike of D614G compared to variants. B. Binding to S-2P of WA1 compared to variants. C. Binding to RBD of WA1 compared to variants.
Figure 6.
Figure 6.. Rank-order of the impact of each variant is similar across assays.
Individual lines and markers show that while the magnitude of the median fold change (compared to WA1/D614G) varies for individual assays, the rank order of impact on antibody recognition by these variants is similar across all assays tested. Median fold change was calculated for all samples. See also Supplemental Table 2.
See this image and copyright information in PMC

References

    1. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). 2021. (https://coronavirus.jhu.edu/map.html ).
    1. Korber B. et al., Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell 182, 812–827 e819 (2020). - PMC - PubMed
    1. Wibmer C. K. et al., SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat Med 27, 622–625 (2021). - PubMed
    1. Wang P. et al., Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7. Nature 593, 130–135 (2021). - PubMed
    1. Shen X. et al., SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host Microbe 29, 529–539 e523 (2021). - PMC - PubMed

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