Development of a broadly active influenza intranasal vaccine adjuvanted with self-assembled particles composed of mastoparan-7 and CpG

被引：3

作者：

Ontiveros-Padilla, Luis ^{[1
]}

Batty, Cole J. J. ^{[1
]}

Hendy, Dylan A. A. ^{[1
]}

Pena, Erik S. S. ^{[2
]}

Roque III, John A. A. ^{[1
]}

Stiepel, Rebeca T. T. ^{[1
]}

Carlock, Michael A. A. ^{[3
,4
]}

Simpson, Sean R. R. ^{[1
]}

Ross, Ted M. M. ^{[3
,4
]}

Abraham, Soman N. N. ^{[5
,6
]}

Staats, Herman F. F. ^{[7
,8
]}

Bachelder, Eric M. M. ^{[1
]}

Ainslie, Kristy M. M. ^{[1
,2
,9
]}

机构：

[1] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA

[2] NC State UNC, Dept Biomed Engn, Chapel Hill, NC 27599 USA

[3] Cleveland Clin Florida, Florida Res & Innovat Ctr, Port St Lucie, FL USA

[4] Univ Georgia, Coll Vet Med, Ctr Vaccines & Immunol, Athens, GA USA

[5] Duke Univ, Sch Med, Dept Pathol Mol Genet & Microbiol, Durham, NC USA

[6] Duke Univ, Sch Med, Dept Immunol, Durham, NC USA

[7] Duke Univ, Sch Med, Dept Pathol, Durham, NC USA

[8] Duke Univ, Duke Human Vaccines Inst, Sch Med, Durham, NC USA

[9] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA

来源：

FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷

基金：

美国国家卫生研究院;

关键词：

Influenza; broadly active vaccine; intranasal; self-assembled particles; mastoparan-7; CpG; MAST-CELL ACTIVATORS; IMMUNE-RESPONSES; NEXT-GENERATION; DNA; VIRUS; COMPOUND-48/80; DELIVERY; MUCOSAL; MICE; OLIGODEOXYNUCLEOTIDES;

D O I：

10.3389/fimmu.2023.1103765

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Currently licensed vaccine adjuvants offer limited mucosal immunity, which is needed to better combat respiratory infections such as influenza. Mast cells (MCs) are emerging as a target for a new class of mucosal vaccine adjuvants. Here, we developed and characterized a nanoparticulate adjuvant composed of an MC activator [mastoparan-7 (M7)] and a TLR ligand (CpG). This novel nanoparticle (NP) adjuvant was co-formulated with a computationally optimized broadly reactive antigen (COBRA) for hemagglutinin (HA), which is broadly reactive against influenza strains. M7 was combined at different ratios with CpG and tested for in vitro immune responses and cytotoxicity. We observed significantly higher cytokine production in dendritic cells and MCs with the lowest cytotoxicity at a charge-neutralizing ratio of nitrogen/phosphate = 1 for M7 and CpG. This combination formed spherical NPs approximately 200 nm in diameter with self-assembling capacity. Mice were vaccinated intranasally with COBRA HA and M7-CpG NPs in a prime-boost-boost schedule. Vaccinated mice had significantly higher antigen-specific antibody responses (IgG and IgA) in serum and mucosa compared with controls. Splenocytes from vaccinated mice had significantly increased cytokine production upon antigen recall and the presence of central and effector memory T cells in draining lymph nodes. Finally, co-immunization with NPs and COBRA HA induced influenza H3N2-specific HA inhibition antibody titers across multiple strains and partially protected mice from a challenge against an H3N2 virus. These results illustrate that the M7-CpG NP adjuvant combination can induce a protective immune response with a broadly reactive influenza antigen via mucosal vaccination.

引用

页数：14