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Using a prime and pull approach, lentivector vaccines expressing Ag85A induce immunogenicity but fail to induce protection against M ycobacterium bovis bacillus Calmette–Guérin challenge in mice
Author(s) -
Britton Gary,
MacDonald Douglas C.,
Brown Jeremy S.,
Collins Mary K.,
Goodman Anna L.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12498
Subject(s) - immunogenicity , tuberculosis vaccines , immunology , immunization , medicine , immune system , adjuvant , vaccination , mycobacterium tuberculosis , tuberculosis , antigen , mycobacterium bovis , nasal administration , bcg vaccine , immunity , virology , pathology
Summary Although bacillus Calmette–Guérin ( BCG ) is an established vaccine with excellent efficacy against disseminated Mycobacterium tuberculosis infection in young children, efficacy in adults suffering from respiratory tuberculosis ( TB ) is suboptimal. Prime‐boost viral vectored vaccines have been shown to induce effective immune responses and lentivectors (LV) have been shown to improve mucosal immunity in the lung. A mucosal boost to induce local immunogenicity is also referred to as a ‘pull’ in a prime and pull approach, which has been found to be a promising vaccine strategy. The majority of infants worldwide receive BCG immunization through current vaccine protocols. We therefore aimed to investigate the role of a boost (or pull) immunization with an LV vaccine expressing the promising TB antigen (Ag85A). We immunized BALB /c mice subcutaneously with BCG or an LV vaccine expressing a nuclear factor‐ κ B activator vFLIP together with Ag85A ( LV vF /85A), then boosted with intranasal LV vF /85A. Prime and pull immunization with LV 85A induced significantly enhanced CD 8 + and CD 4 + T‐cell responses in the lung, but did not protect against intranasal BCG challenge. In contrast, little T‐cell response in the lung was seen when the prime vaccine was BCG , and intranasal vF /85A provided no additional protection against mucosal BCG infection. Our study demonstrates that not all LV prime and pull approaches may be successful against TB in man and careful antigen and immune activator selection is therefore required.