Intranasal Vaccination with Recombinant TLR2-Active Outer Membrane Vesicles Containing Sequential M2e Epitopes Protects against Lethal Influenza a Challenge

被引:1
作者
Kannan, Nisha [1 ]
Choi, Annette [2 ]
De Jesus, Mariela A. Rivera [1 ]
Wei, Peter Male [1 ]
Sahler, Julie Marie [2 ]
Curley, Stephanie Marie [1 ]
August, Avery [2 ]
DeLisa, Matthew P. [3 ]
Whittaker, Gary R. [2 ]
Putnam, David [1 ,3 ]
机构
[1] Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY 14853 USA
[2] Cornell Univ, Dept Microbiol & Immunol, Ithaca, NY 14853 USA
[3] Cornell Univ, Smith Sch Chem & Biomol Engn, Ithaca, NY 14853 USA
基金
美国国家卫生研究院;
关键词
intranasal vaccine; influenza; OMV vaccine; T-CELLS; CROSS-PROTECTION; VIRUS-INFECTION; IGA ANTIBODIES; DELIVERY; VACCINES; IMMUNITY;
D O I
10.3390/vaccines12070724
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Influenza is a highly contagious respiratory disease, resulting in an estimated 3 to 5 million cases of severe illness annually. While most influenza vaccines are administered parenterally via injection, one shortcoming is that they do not generate a strong immune response at the site of infection, which can become important in a pandemic. Intranasal vaccines can generate both local and systemic protective immune responses, can reduce costs, and enhance ease of administration. Previous studies showed that parenterally administered outer membrane vesicles (OMVs) that carry sequences of the M2e protein (OMV-M2e) protect against influenza A/PR8 challenge in mice and ferrets. In the current study, we measured the effectiveness of the intranasal route of the OMV-M2e vaccine against the influenza A/PR8 strain in mice. We observed high anti-M2e IgG and IgA titers post-challenge in mice vaccinated intranasally with OMV-M2e. In addition, we observed a Th1/Tc1 bias in the vaccinated mice, and an increased Th17/Tc17 response, both of which correlated with survival to A/PR8 challenge and significantly lower lung viral titers. We conclude that the intranasal-route administration of the OMV-M2e vaccine is a promising approach toward generating protection against influenza A as it leads to an increased proinflammatory immune response correlating with survival to viral challenge.
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页数:14
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