A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

被引：30

作者：

Jangra, Sonia ^{[1
,2
]}

Landers, Jeffrey J. ^{[3
,4
,5
]}

Rathnasinghe, Raveen ^{[1
,2
,6
]}

O'Konek, Jessica J. ^{[3
,4
,5
]}

Janczak, Katarzyna W. ^{[3
,4
,5
]}

Cascalho, Marilia ^{[7
,8
]}

Kennedy, Andrew A. ^{[3
]}

Tai, Andrew W. ^{[3
,7
,9
]}

Baker, James R., Jr. ^{[3
,4
,5
]}

Schotsaert, Michael ^{[1
,2
]}

Wong, Pamela T. ^{[3
,4
,5
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA

[3] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Michigan Nanotechnol Inst Med & Biol Sci, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Mary H Weiser Food Allergy Ctr, Ann Arbor, MI 48109 USA

[6] Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA

[7] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[8] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI USA

[9] VA Ann Arbor Healthcare Syst, Med Serv, Ann Arbor, MI USA

来源：

FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷

关键词：

SARS-CoV-2; intranasal vaccine; mucosal adjuvant; cross-protection; nanoemulsion (NE); RIG-I agonist; CD8(+) T-CELLS; CELLULAR-IMMUNITY; RIG-I; NANOEMULSION; MUCOSAL; PROTECTION; MEMORY; LUNG; IMMUNIZATION; MICE;

D O I：

10.3389/fimmu.2021.729189

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced T(H)1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.

引用

页数：17

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