Open AccessBoosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection
Author(s) -
Heni Muflihah,
Mário Florido,
Chung-Cherng Lin,
Yingju Xia,
James A. Triccas,
John Stambas,
Warwick J. Britton
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259829
Subject(s) - tuberculosis , mycobacterium tuberculosis , medicine , tuberculosis vaccines , immunology , immunization , virology , immunity , influenza a virus , immune system , vaccination , mycobacterium bovis , virus , pathology
The current Mycobacterium bovis BCG vaccine provides inconsistent protection against pulmonary infection with Mycobacterium tuberculosis . Immunity induced by subcutaneous immunization with BCG wanes and does not promote early recruitment of T cell to the lungs after M . tuberculosis infection. Delivery of Tuberculosis (TB) vaccines to the lungs may increase and prolong immunity at the primary site of M . tuberculosis infection. Pulmonary immunization with recombinant influenza A viruses (rIAVs) expressing an immune-dominant M . tuberculosis CD4 + T cell epitope (PR8-p25 and X31-p25) stimulates protective immunity against lung TB infection. Here, we investigated the potential use of rIAVs to improve the efficacy of BCG using simultaneous immunization (SIM) and prime-boost strategies. SIM with parenteral BCG and intranasal PR8-p25 resulted in equivalent protection to BCG alone against early, acute and chronic M . tuberculosis infection. Boosting BCG with rIAVs increased the frequency of IFN-γ-secreting specific T cells (p<0.001) and polyfunctional CD4 + T cells (p<0.05) in the lungs compared to the BCG alone, however, this did not result in a significant increase in protection against M . tuberculosis compared to BCG alone. Therefore, sequential pulmonary immunization with these rIAVs after BCG increased M . tuberculosis -specific memory T cell responses in the lung, but not protection against M . tuberculosis infection.