Immunization with a Recombinant Bacillus Calmette–Guérin Strain Confers Protective Th1 Immunity against the Human Metapneumovirus

Abstract

Along with the human respiratory syncytial virus (hRSV), the human metapneumovirus (hMPV) is one of the leading causes of childhood hospitalization and a major health burden worldwide. Unfortunately, owing to an inefficient immunological memory, hMPV infection provides limited immune protection against reinfection. Furthermore, hMPV can induce an inadequate Th2 type immune response that causes severe lung inflammation, leading to airway obstruction. Similar to hRSV, it is likely that an effective clearance of hMPV would require a balanced Th1 type immunity by the host, involving the activation of IFN-γ–secreting T cells. A recognized inducer of Th1 immunity is Mycobacterium bovis bacillus Calmette–Guérin (BCG), which has been used in newborns for many decades and in several countries as a tuberculosis vaccine. We have previously shown that immunization with BCG strains expressing hRSV Ags can induce an efficient immune response that protects against this virus. In this study, we show that immunization with rBCG strains expressing the phosphoprotein from hMPV also can induce protective Th1 immunity. Mice immunized with rBCG were protected against weight loss, airway inflammation, and viral replication in the lungs after hMPV infection. Our rBCG vaccine also induced the activation of hMPV-specific T cells producing IFN-γ and IL-2, which could protect from hMPV infection when transferred to recipient mice. These data strongly support the notion that rBCG induces protective Th1 immunity and could be considered as an efficient vaccine against hMPV.

Aberrant T cell immunity triggered by human Respiratory Syncytial Virus and human Metapneumovirus infection

“…31 However, this virus also evades these effective anti-viral immune responses. 26 Moreover, na€ ıve BALB/c mice were shown to develop a biphasic immune response in vivo after hMPV infection.…”

“…[26][27][28][29] The ineffectiveness of the natural infection to induce long-term immunity has hampered vaccine generation and currently there is no licensed vaccine available to prevent the bronchiolitis and pneumonia caused either by hRSV or hMPV. [30][31][32][33][34] However, several candidate vaccines are in different stages of development for preventing the diseases caused by these viral agents. Candidate vaccines for hRSV and hMPV employ different approaches, including a chimeric virus (hMPV), 35 live attenuated virus (hRSV), 36 and purified proteins (hRSV), 37 among others.…”

“…Furthermore, recombinant Bacillus Calmette-Gu erin (rBCG) vaccines have been developed using hRSV and hMPV antigens to provide a protective T H 1 response in mice. 31,38,39 In addition, antibody-mediated immunity is relevant for protection against both viruses. 40,41 For example, Palivizumab, an IgG1 humanized anti-F monoclonal antibody, is safe and effective when given in a prophylactic manner to children at risk of severe hRSV infection.…”

Assessment of recombinant plasmid expressing fusion antigen Ag85B-Rv3425 in management of acute tuberculosis infection in mice

“…In our study, we found that recombinant plasmid A3-Vec, like lentivirus delivered A3 (11), could induce A3 fusion protein specific antibody IgG response, indicating that it could be expressed in mice and then recognized by immune system. Moreover, we have observed immunization of plasmid A3-Vec could induce high Th1-type cytokines production, such as IL-2 and TNF-α (22), in spleen lymphocytes in A3-Vec treated mice. Moreover, recombinant plasmid A3-Vec shows potent effective therapeutic effect in acute Mtb infected mice.…”

Recent vaccine development for human metapneumovirus

“…Other hMPV proteins which have been used for proteinbased vaccine development include the P and G proteins (Lévy et al, 2013;Palavecino et al, 2014). A recombinant bacillus Calmette-Guerin (a carrier to promote an immune response against antigens from other bacterial, parasitic and viral pathogens) expressing hMPV P protein is able to confer strong effector phenotypes to both CD4 + and CD8 + T cells, which showed protective hMPV immunity equivalent to actively immunized animals.…”