Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses

被引：162

作者：

Mao, Tianyang

Israelow, Benjamin

Pena-Hernandez, Mario A.

Suberi, Alexandra

Zhou, Liqun

Luyten, Sophia

Reschke, Melanie

Dong, Huiping

Homer, Robert J.

Saltzman, W. Mark

Iwasaki, Akiko

机构：

[1] Department of Immunobiology, Yale University School of Medicine, New Haven, CT

[2] Section of Infectious Diseases, Department of Medicine, Yale University School of Medicine, New Haven, CT

[3] Department of Biomedical Engineering, Yale University, New Haven, CT

[4] Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT

[5] Department of Pathology, Yale University School of Medicine, New Haven, CT

[6] Department of Chemical and Environmental Engineering, Yale University, New Haven, CT

[7] Department of Cellular and Molecular Physiology, Yale University, New Haven, CT

[8] Department of Dermatology, Yale University, New Haven, CT

[9] Howard Hughes Medical Institute, Chevy Chase, MD

来源：

SCIENCE | 2022年 / 378卷 / 6622期

关键词：

SARS-COV-2;

D O I：

10.1126/science.abo2523

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also prevent transmission. Parenteral vaccines induce robust systemic immunity but poor immunity at the respiratory mucosa. We developed a vaccine strategy that we call "prime and spike," which leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract by using unadjuvanted intranasal spike boosters (spike). We show that prime and spike induces robust resident memory B and T cell responses, induces immunoglobulin A at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables the induction of cross-reactive immunity against sarbecoviruses.

引用

页码：872 / +

页数：13

共 45 条

[1] The establishment of resident memory B cells in the lung requires local antigen encounter [J].

Allie, S. Rameeza ;

Bradley, John E. ;

Mudunuru, Uma ;

Schultz, Michael D. ;

Graf, Beth A. ;

Lund, Frances E. ;

Randall, Troy D. .

NATURE IMMUNOLOGY, 2019, 20 (01) :97-+

[2]

Amanat F, 2020, NAT MED, V26, P1033, DOI [10.1038/s41591-020-0913-5, 10.1101/2020.03.17.20037713]

[3] 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

[4]

Bricker Traci L, 2020, bioRxiv, DOI [10.1016/j.celrep.2021.109400, 10.1101/2020.12.02.408823]

[5] Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization [J].

Cele, Sandile ;

Jackson, Laurelle ;

Khoury, David S. ;

Khan, Khadija ;

Moyo-Gwete, Thandeka ;

Tegally, Houriiyah ;

San, James Emmanuel ;

Cromer, Deborah ;

Scheepers, Cathrine ;

Amoako, Daniel G. ;

Karim, Farina ;

Bernstein, Mallory ;

Lustig, Gila ;

Archary, Derseree ;

Smith, Muneerah ;

Ganga, Yashica ;

Jule, Zesuliwe ;

Reedoy, Kajal ;

Hwa, Shi-Hsia ;

Giandhari, Jennifer ;

Blackburn, Jonathan M. ;

Gosnell, Bernadett, I ;

Karim, Salim S. Abdool ;

Hanekom, Willem ;

von Gottberg, Anne ;

Bhiman, Jinal N. ;

Lessells, Richard J. ;

Moosa, Mahomed-Yunus S. ;

Davenport, Miles P. ;

de Oliveira, Tulio ;

Moore, Penny L. ;

Sigal, Alex .

NATURE, 2022, 602 (7898) :654-+

[6] Waning of BNT162b2 Vaccine Protection against SARS-CoV-2 Infection in Qatar [J].

Chemaitelly, Hiam ;

Tang, Patrick ;

Hasan, Mohammad R. ;

AlMukdad, Sawsan ;

Yassine, Hadi M. ;

Benslimane, Fatiha M. ;

Al Khatib, Hebah A. ;

Coyle, Peter ;

Ayoub, Houssein H. ;

Al Kanaani, Zaina ;

Al Kuwari, Einas ;

Jeremijenko, Andrew ;

Kaleeckal, Anvar H. ;

Latif, Ali N. ;

Shaik, Riyazuddin M. ;

Rahim, Hanan F. Abdul ;

Nasrallah, Gheyath K. ;

Al Kuwari, Mohamed G. ;

Al Romaihi, Hamad E. ;

Butt, Adeel A. ;

Al-Thani, Mohamed H. ;

Al Khal, Abdullatif ;

Bertollini, Roberto ;

Abu-Raddad, Laith J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 385 (24) :E83-E83

[7] SARS-CoV-2 vaccine protection and deaths among US veterans during 2021 [J].

Cohn, Barbara A. ;

Cirillo, Piera M. ;

Murphy, Caitlin C. ;

Krigbaum, Nickilou Y. ;

Wallace, Arthur W. .

SCIENCE, 2022, 375 (6578) :331-+

[8] BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting [J].

Dagan, Noa ;

Barda, Noam ;

Kepten, Eldad ;

Miron, Oren ;

Perchik, Shay ;

Katz, Mark A. ;

Hernan, Miguel A. ;

Lipsitch, Marc ;

Reis, Ben ;

Balicer, Ran D. .

NEW ENGLAND JOURNAL OF MEDICINE, 2021, 384 (15) :1412-1423

[9] Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial [J].

Emary, Katherine R. W. ;

Golubchik, Tanya ;

Aley, Parvinder K. ;

Ariani, Cristina, V ;

Angus, Brian ;

Bibi, Sagida ;

Blane, Beth ;

Bonsall, David ;

Cicconi, Paola ;

Charlton, Sue ;

Clutterbuck, Elizabeth A. ;

Collins, Andrea M. ;

Cox, Tony ;

Darton, Thomas C. ;

Dold, Christina ;

Douglas, Alexander D. ;

Duncan, Christopher J. A. ;

Ewer, Katie J. ;

Flaxman, Amy L. ;

Faust, Saul N. ;

Ferreira, Daniela M. ;

Feng, Shuo ;

Finn, Adam ;

Folegatti, Pedro M. ;

Fuskova, Michelle ;

Galiza, Eva ;

Goodman, Anna L. ;

Green, Catherine M. ;

Green, Christopher A. ;

Greenland, Melanie ;

Hallis, Bassam ;

Heath, Paul T. ;

Hay, Jodie ;

Hill, Helen C. ;

Jenkin, Daniel ;

Kerridge, Simon ;

Lazarus, Rajeka ;

Libri, Vincenzo ;

Lillie, Patrick J. ;

Ludden, Catherine ;

Marchevsky, Natalie G. ;

Minassian, Angela M. ;

McGregor, Alastair C. ;

Mujadidi, Yama F. ;

Phillips, Daniel J. ;

Plested, Emma ;

Pollock, Katrina M. ;

Robinson, Hannah ;

Smith, Andrew ;

Song, Rinn .

LANCET, 2021, 397 (10282) :1351-1362

[10] Prime-boost strategies in mucosal immunization affect local IgA production and tne type of Th response [J].

Fiorino, Fabio ;

Pettini, Elena ;

Pozzi, Gianni ;

Medaglini, Donata ;

Ciabattini, Annalisa .

FRONTIERS IN IMMUNOLOGY, 2013, 4

← 1 2 3 4 5 →