Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

被引：48

作者：

Nouailles, Geraldine ^{[1
,2
,3
]}

Adler, Julia M. ^{[1
,2
,3
,4
]}

Pennitz, Peter ^{[1
,2
,3
]}

Peidli, Stefan ^{[3
,5
,6
]}

Teixeira Alves, Luiz Gustavo ^{[7
]}

Baumgardt, Morris ^{[1
,2
,3
]}

Bushe, Judith ^{[8
]}

Voss, Anne ^{[8
]}

Langenhagen, Alina ^{[8
]}

Langner, Christine

Martin Vidal, Ricardo

Pott, Fabian ^{[3
,9
,10
,11
]}

Kazmierski, Julia ^{[3
,9
,10
,11
]}

Ebenig, Aileen ^{[12
]}

Lange, Mona V. ^{[12
]}

Muehlebach, Michael D. ^{[12
,13
]}

Goekeri, Cengiz ^{[14
]}

Simmons, Szandor ^{[3
,10
,15
]}

Xing, Na

Abdelgawad, Azza

Herwig, Susanne ^{[3
,10
,16
]}

Cichon, Guenter ^{[3
,10
,16
]}

Niemeyer, Daniela ^{[17
]}

Drosten, Christian ^{[3
,9
,10
,17
]}

Goffinet, Christine ^{[3
,9
,10
,11
]}

Landthaler, Markus ^{[7
,18
]}

Bluethgen, Nils ^{[3
,4
,5
,6
]}

Wu, Haibo ^{[19
]}

Witzenrath, Martin

Gruber, Achim D. ^{[8
]}

Praktiknjo, Samantha D. ^{[20
]}

Osterrieder, Nikolaus ^{[4
,21
]}

Wyler, Emanuel ^{[7
]}

Kunec, Dusan ^{[4
]}

Trimpert, Jakob ^{[4
]}

机构：

[1] Charite Univ Med Berlin, Dept Infect Dis, Resp Med & Crit Care, Berlin, Germany

[2] Univ Berlin, Berlin, Germany

[3] Humboldt Univ, Berlin, Germany

[4] Free Univ Berlin, Inst Virol, Berlin, Germany

[5] Charite Univ Klinikum Berlin, Inst Pathol, Berlin, Germany

[6] Humboldt Univ, Inst Biol, IRI Life Sci, Berlin, Germany

[7] Max Delbruck Ctr Mol Med Helmholtz Assoc, Berlin Inst Med Syst Biol, Berlin, Germany

[8] Freie Univ Berlin Berlin, Inst Tierpathol, Berlin, Germany

[9] Charite Univ Med Berlin, Inst Virol, Berlin, Germany

[10] Free Univ Berlin, Berlin, Germany

[11] Berlin Inst Hlth, Berlin, Germany

[12] Paul Ehrlich Inst, Product Testing IVMPs, Div Vet Med, Langen, Germany

[13] German Ctr Infect Res, Partner site Giessen Marburg Langen, Giessen, Germany

[14] Cyprus Int Univ, Fac Med, Nicosia, Cyprus

[15] Charite Univ Med Berlin, Inst Physiol, Berlin, Germany

[16] Charite Univ Med Berlin, Dept Gynecol, Berlin, Germany

[17] German Ctr Infect Res DZIF, Partner site Charite, Berlin, Germany

[18] Humboldt Univ, Inst Biol, Berlin, Germany

[19] Chongqing Univ, Sch Life Sci, Chongqing, Peoples R China

[20] Charite Univ Med Berlin, Berlin Inst Hlth, Berlin, Germany

[21] City Univ Hong Kong, Dept Infect Dis & Publ Hlth, Jockey Club Coll Vet Med & Life Sci, Kowloon, Hong Kong, Peoples R China

来源：

NATURE MICROBIOLOGY | 2023年 / 8卷 / 5期

关键词：

T-CELLS; IMMUNIZATION; INTRANASAL; PROTECTS;

D O I：

10.1038/s41564-023-01352-8

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Comparison of mucosal and systemic immunity after vaccination with the live-attenuated vaccine sCPD9, mRNA vaccine BNT162b2 or an adenovirus-vectored vaccine following SARS-CoV-2 challenge in hamsters. Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

引用

页码：860 / 874

页数：24

共 62 条

[1] Respiratory mucosal delivery of next-generation COVID-19 vaccine provides robust protection against both ancestral and variant strains of SARS-CoV-2 [J].

Afkhami, Sam ;

D'Agostino, Michael R. ;

Zhang, Ali ;

Stacey, Hannah D. ;

Marzok, Art ;

Kang, Alisha ;

Singh, Ramandeep ;

Bavananthasivam, Jegarubee ;

Ye, Gluke ;

Luo, Xiangqian ;

Wang, Fuan ;

Ang, Jann C. ;

Zganiacz, Anna ;

Sankar, Uma ;

Kazhdan, Natallia ;

Koenig, Joshua F. E. ;

Phelps, Allyssa ;

Gameiro, Steven F. ;

Tang, Shangguo ;

Jordana, Manel ;

Wan, Yonghong ;

Mossman, Karen L. ;

Jeyanathan, Mangalakumari ;

Gillgrass, Amy ;

Medina, Maria Fe C. ;

Smaill, Fiona ;

Lichty, Brian D. ;

Miller, Matthew S. ;

Xing, Zhou .

CELL, 2022, 185 (05) :896-+

[2]

[Anonymous], 2011, Can Commun Dis Rep, V37, P1

[3]

[Anonymous], 2022, COVID 19 VACC WHO EM

[4]

[Anonymous], 2022, COVID-19 Tracker

[5]

[Anonymous], 2022, COVID-19 vaccine surveillance report

[6] SARS-CoV-2 infection of Chinese hamsters (Cricetulus griseus) reproduces COVID-19 pneumonia in a well-established small animal model [J].

Bertzbach, Luca D. ;

Vladimirova, Daria ;

Dietert, Kristina ;

Abdelgawad, Azza ;

Gruber, Achim D. ;

Osterrieder, Nikolaus ;

Trimpert, Jakob .

TRANSBOUNDARY AND EMERGING DISEASES, 2021, 68 (03) :1075-1079

[7] CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses [J].

Beura, Lalit K. ;

Fares-Frederickson, Nancy J. ;

Steinert, Elizabeth M. ;

Scott, Milcah C. ;

Thompson, Emily A. ;

Fraser, Kathryn A. ;

Schenke, Jason M. ;

Vezys, Vaiva ;

Masopust, David .

JOURNAL OF EXPERIMENTAL MEDICINE, 2019, 216 (05) :1214-1229

[8] Immune responses after omicron infection in triple-vaccinated health-care workers with and without previous SARS-CoV-2 infection [J].

Blom, Kim ;

Marking, Ulrika ;

Havervall, Sebastian ;

Norin, Nina Greilert ;

Gordon, Max ;

Garcia, Marina ;

Tecleab, Teghesti ;

Christ, Wanda ;

Forsell, Mattias ;

Phillipson, Mia ;

Nilsson, Peter ;

Mangsbo, Sara ;

Hober, Sophia ;

Aberg, Mikael ;

Klingstrom, Jonas ;

Thalin, Charlotte .

LANCET INFECTIOUS DISEASES, 2022, 22 (07) :943-945

[9] Secretory immunity with special reference to the oral cavity [J].

Brandtzaeg, Per .

JOURNAL OF ORAL MICROBIOLOGY, 2013, 5

[10] SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19 [J].

Braun, Julian ;

Loyal, Lucie ;

Frentsch, Marco ;

Wendisch, Daniel ;

Georg, Philipp ;

Kurth, Florian ;

Hippenstiel, Stefan ;

Dingeldey, Manuela ;

Kruse, Beate ;

Fauchere, Florent ;

Baysal, Emre ;

Mangold, Maike ;

Henze, Larissa ;

Lauster, Roland ;

Mall, Marcus A. ;

Beyer, Kirsten ;

Roehmel, Jobst ;

Voigt, Sebastian ;

Schmitz, Juergen ;

Miltenyi, Stefan ;

Demuth, Ilja ;

Mueller, Marcel A. ;

Hocke, Andreas ;

Witzenrath, Martin ;

Suttorp, Norbert ;

Kern, Florian ;

Reimer, Ulf ;

Wenschuh, Holger ;

Drosten, Christian ;

Corman, Victor M. ;

Giesecke-Thiel, Claudia ;

Sander, Leif Erik ;

Thiel, Andreas .

NATURE, 2020, 587 (7833) :270-+

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