Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis

被引：283

作者：

Choi, Angela ^{[1
]}

Koch, Matthew ^{[1
]}

Wu, Kai ^{[1
]}

Chu, Laurence ^{[2
]}

Ma, LingZhi ^{[1
]}

Hill, Anna ^{[1
]}

Nunna, Naveen ^{[1
]}

Huang, Wenmei ^{[1
]}

Oestreicher, Judy ^{[1
]}

Colpitts, Tonya ^{[1
]}

Bennett, Hamilton ^{[1
]}

Legault, Holly ^{[1
]}

Paila, Yamuna ^{[1
]}

Nestorova, Biliana ^{[1
]}

Ding, Baoyu ^{[1
]}

Montefiori, David ^{[3
]}

Pajon, Rolando ^{[1
]}

Miller, Jacqueline M. ^{[1
]}

Leav, Brett ^{[1
]}

Carfi, Andrea ^{[1
]}

McPhee, Roderick ^{[1
]}

Edwards, Darin K. ^{[1
]}

机构：

[1] Moderna Inc, Cambridge, MA 02139 USA

[2] Benchmark Res, Austin, TX USA

[3] Duke Univ, Med Ctr, Immune Assay Team, Durham, NC USA

来源：

NATURE MEDICINE | 2021年 / 27卷 / 11期

关键词：

D O I：

10.1038/s41591-021-01527-y

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study (NCT04405076) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 (P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs.

引用

页码：2025 / +

页数：13

共 14 条

[1] Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults [J].

Anderson, E. J. ;

Rouphael, N. G. ;

Widge, A. T. ;

Jackson, L. A. ;

Roberts, P. C. ;

Makhene, M. ;

Chappell, J. D. ;

Denison, M. R. ;

Stevens, L. J. ;

Pruijssers, A. J. ;

McDermott, A. B. ;

Flach, B. ;

Lin, B. C. ;

Doria-Rose, N. A. ;

O'Dell, S. ;

Schmidt, S. D. ;

Corbett, K. S. ;

Swanson, P. A., II ;

Padilla, M. ;

Neuzil, K. M. ;

Bennett, H. ;

Leav, B. ;

Makowski, M. ;

Albert, J. ;

Cross, K. ;

Edara, V. V. ;

Floyd, K. ;

Suthar, M. S. ;

Martinez, D. R. ;

Baric, R. ;

Buchanan, W. ;

Luke, C. J. ;

Phadke, V. K. ;

Rostad, C. A. ;

Ledgerwood, J. E. ;

Graham, B. S. ;

Beigel, J. H. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (25) :2427-2438

[2] Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine [J].

Baden, Lindsey R. ;

El Sahly, Hana M. ;

Essink, Brandon ;

Kotloff, Karen ;

Frey, Sharon ;

Novak, Rick ;

Diemert, David ;

Spector, Stephen A. ;

Rouphael, Nadine ;

Creech, C. Buddy ;

McGettigan, John ;

Khetan, Shishir ;

Segall, Nathan ;

Solis, Joel ;

Brosz, Adam ;

Fierro, Carlos ;

Schwartz, Howard ;

Neuzil, Kathleen ;

Corey, Larry ;

Gilbert, Peter ;

Janes, Holly ;

Follmann, Dean ;

Marovich, Mary ;

Mascola, John ;

Polakowski, Laura ;

Ledgerwood, Julie ;

Graham, Barney S. ;

Bennett, Hamilton ;

Pajon, Rolando ;

Knightly, Conor ;

Leav, Brett ;

Deng, Weiping ;

Zhou, Honghong ;

Han, Shu ;

Ivarsson, Melanie ;

Miller, Jacqueline ;

Zaks, Tal .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (05) :403-416

[3]

Choi A., SERUM NEUTRALIZING A, DOI [10.1101/2021.06.28.449914v1(2021), DOI 10.1101/2021.06.28.449914V1(2021)]

[4] A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine [J].

Chu, Laurence ;

McPhee, Roderick ;

Huang, Wenmei ;

Bennett, Hamilton ;

Pajon, Rolando ;

Nestorova, Biliana ;

Leav, Brett .

VACCINE, 2021, 39 (20) :2791-2799

[5] Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19 [J].

Doria-Rose, Nicole ;

Suthar, Mehul S. ;

Makowski, Mat .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (23) :2259-2261

[6] An mRNA Vaccine against SARS-CoV-2-Preliminary Report [J].

Jackson, L. A. ;

Anderson, E. J. ;

Rouphael, N. G. ;

Roberts, P. C. ;

Makhene, M. ;

Coler, R. N. ;

McCullough, M. P. ;

Chappell, J. D. ;

Denison, M. R. ;

Stevens, L. J. ;

Pruijssers, A. J. ;

McDermott, A. ;

Flach, B. ;

Doria-Rose, N. A. ;

Corbett, K. S. ;

Morabito, K. M. ;

O'Dell, S. ;

Schmidt, S. D. ;

Swanson, P. A. ;

Padilla, M. ;

Mascola, J. R. ;

Neuzil, K. M. ;

Bennett, H. ;

Sun, W. ;

Peters, E. ;

Makowski, M. ;

Albert, J. ;

Cross, K. ;

Buchanan, W. ;

Pikaart-Tautges, R. ;

Ledgerwood, J. E. ;

Graham, B. S. ;

Beigel, J. H. .

NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (20) :1920-1931

[7] Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection [J].

Khoury, David S. ;

Cromer, Deborah ;

Reynaldi, Arnold ;

Schlub, Timothy E. ;

Wheatley, Adam K. ;

Juno, Jennifer A. ;

Subbarao, Kanta ;

Kent, Stephen J. ;

Triccas, James A. ;

Davenport, Miles P. .

NATURE MEDICINE, 2021, 27 (07) :1205-+

[8] Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant [J].

Madhi, S. A. ;

Baillie, V ;

Cutland, C. L. ;

Voysey, M. ;

Koen, A. L. ;

Fairlie, L. ;

Padayachee, S. D. ;

Dheda, K. ;

Barnabas, S. L. ;

Bhorat, Q. E. ;

Briner, C. ;

Kwatra, G. ;

Ahmed, K. ;

Aley, P. ;

Bhikha, S. ;

Bhiman, J. N. ;

Bhorat, A' E. ;

du Plessis, J. ;

Esmail, A. ;

Groenewald, M. ;

Horne, E. ;

Hwa, S-H ;

Jose, A. ;

Lambe, T. ;

Laubscher, M. ;

Malahleha, M. ;

Masenya, M. ;

Masilela, M. ;

McKenzie, S. ;

Molapo, K. ;

Moultrie, A. ;

Oelofse, S. ;

Patel, F. ;

Pillay, S. ;

Rhead, S. ;

Rodel, H. ;

Rossouw, L. ;

Taoushanis, C. ;

Tegally, H. ;

Thombrayil, A. ;

van Eck, S. ;

Wibmer, C. K. ;

Durham, N. M. ;

Kelly, E. J. ;

Villafana, T. L. ;

Gilbert, S. ;

Pollard, A. J. ;

de Oliveira, T. ;

Moore, P. L. ;

Sigal, A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (20) :1885-1898

[9] Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis of Randomized Clinical Trials [J].

Pormohammad, Ali ;

Zarei, Mohammad ;

Ghorbani, Saied ;

Mohammadi, Mehdi ;

Razizadeh, Mohammad Hossein ;

Turner, Diana L. ;

Turner, Raymond J. .

VACCINES, 2021, 9 (05)

[10]

Shen Xiaoying, 2021, Cell Host Microbe, V29, P529, DOI [10.1016/j.chom.2021.03.002, 10.1101/2021.01.27.428516]

← 1 2 →