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T cell responses induced by adenoviral vectored vaccines can be adjuvanted by fusion of antigen to the oligomerization domain of C4b-binding protein.

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Forbes, Emily K, de Cassan, Simone C, Llewellyn, David, Biswas, Sumi, Goodman, Anna L, Cottingham, Matthew G, Long, Carole A, Pleass, Richard ORCID: https://orcid.org/0000-0001-7438-8296, Hill, Adrian V S, Hill, Fergal and Draper, Simon J (2012) 'T cell responses induced by adenoviral vectored vaccines can be adjuvanted by fusion of antigen to the oligomerization domain of C4b-binding protein.'. PLoS ONE, Vol 7, Issue 9, e44943.

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Abstract

Viral vectored vaccines have been shown to induce both T cell and antibody responses in animals and humans. However, the induction of even higher level T cell responses may be crucial in achieving vaccine efficacy against difficult disease targets, especially in humans. Here we investigate the oligomerization domain of the α-chain of C4b-binding protein (C4 bp) as a candidate T cell "molecular adjuvant" when fused to malaria antigens expressed by human adenovirus serotype 5 (AdHu5) vectored vaccines in BALB/c mice. We demonstrate that i) C-terminal fusion of an oligomerization domain can enhance the quantity of antigen-specific CD4(+) and CD8(+) T cell responses induced in mice after only a single immunization of recombinant AdHu5, and that the T cells maintain similar functional cytokine profiles; ii) an adjuvant effect is observed for AdHu5 vectors expressing either the 42 kDa C-terminal domain of Plasmodium yoelii merozoite surface protein 1 (PyMSP1(42)) or the 83 kDa ectodomain of P. falciparum strain 3D7 apical membrane antigen 1 (PfAMA1), but not a candidate 128kDa P. falciparum MSP1 biallelic fusion antigen; iii) following two homologous immunizations of AdHu5 vaccines, antigen-specific T cell responses are further enhanced, however, in both BALB/c mice and New Zealand White rabbits no enhancement of functional antibody responses is observed; and iv) that the T cell adjuvant activity of C4 bp is not dependent on a functional Fc-receptor γ-chain in the host, but is associated with the oligomerization of small (<80 kDa) antigens expressed by recombinant AdHu5. The oligomerization domain of C4 bp can thus adjuvant T cell responses induced by AdHu5 vectors against selected antigens and its clinical utility as well as mechanism of action warrant further investigation.

Item Type: Article
Subjects: QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
WC Communicable Diseases > Virus Diseases > General Virus Diseases > WC 500 Virus diseases (General or not elsewhere classified)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pone.0044943
Depositing User: Mary Creegan
Date Deposited: 01 Mar 2013 11:25
Last Modified: 06 Feb 2018 13:05
URI: http://archive.lstmed.ac.uk/id/eprint/3265

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