Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Tully, Claire M and Chinnakannan, Senthil and Mullarkey, Caitlin E and Ulaszewska, Marta and Ferrara, Francesca and Temperton, Nigel J. and Gilbert, Sarah C and Lambe, Teresa (2017) Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge. Journal of immunology, 199 (4). pp. 1333-1341. ISSN 1550-6606. E-ISSN 1550-6606. (doi:https://doi.org/10.4049/jimmunol.1600939) (Full text available)

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Abstract

Seasonal influenza viruses are a common cause of acute respiratory illness worldwide and generate a significant socioeconomic burden. Influenza viruses mutate rapidly, necessitating annual vaccine reformulation because traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality compared with seasonal strains. Ongoing strategies to improve vaccine efficacy typically focus on providing broad-spectrum immunity; although B and T cells can mediate heterosubtypic responses, typical vaccine development will augment either humoral or cellular immunity. However, multipronged approaches that target several Ags may limit the generation of viral escape mutants. There are few vaccine platforms that can deliver multiple Ags and generate robust cellular and humoral immunity. In this article, we describe a novel vaccination strategy, tested preclinically in mice, for the delivery of novel bivalent viral-vectored vaccines. We show this strategy elicits potent T cell responses toward highly conserved internal Ags while simultaneously inducing high levels of Abs toward hemagglutinin. Importantly, these humoral responses generate long-lived plasma cells and generate Abs capable of neutralizing variant hemagglutinin-expressing pseudotyped lentiviruses. Significantly, these novel viral-vectored vaccines induce strong immune responses capable of conferring protection in a stringent influenza A virus challenge. Thus, this vaccination regimen induces lasting efficacy toward influenza. Importantly, the simultaneous delivery of dual Ags may alleviate the selective pressure that is thought to potentiate antigenic diversity in avian influenza viruses.

Item Type: Article
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 21 Jul 2017 19:08 UTC
Last Modified: 29 Aug 2017 15:40 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/62379 (The current URI for this page, for reference purposes)
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