Rosario, Maximillian, Hopkins, Richard, Fulkerson, John, Borthwick, Nicola, Quigley, Maire F., Joseph, Joan, Douek, Daniel C., Greenaway, Hui Yee, Venturi, Vanessa, Gostick, Emma, Price, David  ORCID: https://orcid.org/0000-0001-9416-2737, Both, Gerald W., Sadoff, Jerald C. and Hanke, Tomas
2010.
Novel recombinant mycobacterium bovis BCG, ovine atadenovirus, and modified vaccinia virus ankara vaccines combine to induce robust human immunodeficiency virus-specific CD4 and CD8 T-cell responses in rhesus macaques.
Journal of Virology
84
(12)
, pp. 5898-5908.
10.1128/JVI.02607-09
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Abstract
Mycobacterium bovis bacillus Calmette-Guérin (BCG), which elicits a degree of protective immunity against tuberculosis, is the most widely used vaccine in the world. Due to its persistence and immunogenicity, BCG has been proposed as a vector for vaccines against other infections, including HIV-1. BCG has a very good safety record, although it can cause disseminated disease in immunocompromised individuals. Here, we constructed a recombinant BCG vector expressing HIV-1 clade A-derived immunogen HIVA using the recently described safer and more immunogenic BCG strain AERAS-401 as the parental mycobacterium. Using routine ex vivo T-cell assays, BCG.HIVA401 as a stand-alone vaccine induced undetectable and weak CD8 T-cell responses in BALB/c mice and rhesus macaques, respectively. However, when BCG.HIVA401 was used as a priming component in heterologous vaccination regimens together with recombinant modified vaccinia virus Ankara-vectored MVA.HIVA and ovine atadenovirus-vectored OAdV.HIVA vaccines, robust HIV-1-specific T-cell responses were elicited. These high-frequency T-cell responses were broadly directed and capable of proliferation in response to recall antigen. Furthermore, multiple antigen-specific T-cell clonotypes were efficiently recruited into the memory pool. These desirable features are thought to be associated with good control of HIV-1 infection. In addition, strong and persistent T-cell responses specific for the BCG-derived purified protein derivative (PPD) antigen were induced. This work is the first demonstration of immunogenicity for two novel vaccine vectors and the corresponding candidate HIV-1 vaccines BCG.HIVA401 and OAdV.HIVA in nonhuman primates. These results strongly support their further exploration.
| Item Type: | Article |
|---|---|
| Status: | Published |
| Schools: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | Q Science > QR Microbiology |
| Additional Information: | Pdf uploaded in accordance with publisher's policy at http://www.sherpa.ac.uk/romeo/issn/0022-538X/ (accessed 25/02/2014) |
| Publisher: | American Society for Microbiology |
| ISSN: | 0022-538X |
| Date of First Compliant Deposit: | 30 March 2016 |
| Last Modified: | 16 May 2023 12:05 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/27554 |
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